Sarcophyton digitatum resulted in the isolation and structural identification of four new biscembranoidal metabolites, sardigitolides A–D (1–4), along with three previously isolated biscembranoids, sarcophytolide L (5), glaucumolide A (6), glaucumolide B (7), and two known cembranoids (8 and 9). The chemical structures of all isolates were elucidated on the basis of 1D and 2D NMR spectroscopic analyses. Additionally, in order to discover bioactivity of marine natural products, 1–8 were examined in terms of their inhibitory potential against the upregulation of inflammatory factor production in lipopolysaccharide (LPS)-stimulated murine macrophage J774A.1 cells and their cytotoxicities against a limited panel of cancer cells. The anti-inflammatory results showed that at a concentration of 10 µg/mL, 6 and 8 inhibited the production of IL-1β to 68 ± 1 and 56 ± 1%, respectively, in LPS-stimulated murine macrophages J774A.1. Furthermore, sardigitolide B (2) displayed cytotoxicities toward MCF-7 and MDA-MB-231 cancer cell lines with the IC50 values of 9.6 ± 3.0 and 14.8 ± 4.0 µg/mL, respectively.Chemical examination from the cultured soft coral  Cembrane diterpenoids and their derivatives are an abundant and structurally diverse group of secondary metabolites of soft corals and gorgonians. The 14-membered ring structures of cembranoids are biosynthetically formed by cyclization of a geranylgeranyl pyrophosphate precursor between carbons 1 and 14 . CembranSarcophyton are rich sources of compounds, such as cembranoids -hexadeca-4,12,14-trien-18-one (9) [1–8 against the enhanced production of inflammatory factors in LPS-treated murine macrophage J774A.1 cells was examined. Furthermore, the in vitro cytotoxicities toward MCF-7, MDA-MB-231, HepG2, and HeLa cells of compounds 1–8 were investigated.Previous studies indicated that species of branoids ,14,15,16branoids ,19,20,21branoids . Until ncophyton . It is w species . Due to de L (5) , glaucum (5) [6) , glaucum [6) [7) , isosarc [7) [8) , and (4Z-one (9) . Lipopol-one (9) . In the Sarcophyton digitatum was cultured in the National Museum of Marine Biology & Aquarium. A frozen sample was initially extracted with n-hexane and subsequently by ethyl acetate. The ethyl acetate layer was concentrated and repeatedly chromatographed to isolate compounds 1–9  was isolated as a white amorphous powder. High-resolution electron spray ionization mass spectroscopy (HRESIMS) showed a molecular ion peak at m/z 721.4287 −1 indicated the presence of a hydroxy group. The 13C spectrum , two methyl groups linked to oxygen-bearing quaternary carbons , one methoxy group , an isopropyl group , one tetrasubstituted double bond , three oxygen-bearing methines , two oxygen-bearing quaternary carbons , and four carbonyl carbons . All of the above evidence suggested that 1 contained a biscembranoid skeleton. The planar structure of 1 was further determined. The correlations spectroscopy (COSY) signals revealed eight different structural units from H-2 to H2-36; H2-6 via H2-7 and H2-8; H-9 to H3-18; isopropyl protons H3-16 and H3-17 via H-15, H-12, and H-11; H-21 to H-22; H2-24 via H2-25 and H2-26; H2-28 via H2-29 and H-30; and H2-32 to H-33. These units were assembled by heteronuclear multiple bond correlations (HMBCs) of H3-16 to C-12, C-15, and C-17; H3-18 to C-8, C-9, and C-10; H3-19 to C-4, C-5, and C-6; H3-37 to C-34, C-35, and C-36; H3-38 to C-22, C-23, and C-24; H3-39 to C-27, C-28, and C-29; H3-40 to C-30, C-31, and C-32; H-2 to C-1, C-3, and C-14; H2-11 to C-10; H-12 to C-13; H2-14 to C-1 and C-20; and H-33 to C-34 and C-35. Accordingly, compound 1 had an additional degree of unsaturation, which was suggested to be of an ether ring between C-26 and C-30 established via an HMBC from H-26 to C-30. The gross structure of 1 was thus confirmed as shown in Sardigitolide A . As shown in δH 6.44, s) with H3-19 , together with the obviously downfield-shifted methyl group at C-19 , suggested a cis geometry of C-4/C-5 trisubstituted double bond. Assuming the β-orientations of H3-41 as previously reported [3-41 with both of H3-16  and H3-17 , and all of H3-16, H3-17 and H3-18  with H-11  suggested the β-orientations of H3-18 and C-1 carbomethoxy groups, on the basis that metabolites of this type with absolute configurations determined previously all possessed 1S and 2S configurations [δH 5.06, d, J = 10.0 Hz); H-22 with H-24β ; and H-24β with H-25β ; H-25β with H3-39 ; H3-39 with H-28β ; H-28β with H-30  reflected the β-orientation of H-30 and H3-39. In contrast, the α-orientations of H-9 and H-12 were confirmed by the NOE correlations of H-11α  with both H-9  and H-12 . The α-orientation of H-26 was determined by the NOE correlations of H-21  with H3-38 ; H3-38 with H-24α ; H-24α with H-25α ; H-25α with H-26 . Also, the α-orientations of H-33 and H3-40 were determined by the NOE correlations of H-33  with both H3-37  and H3-40 . Moreover, the 13C NMR signals of C-37  and C-38  indicated the E geometry of the trisubstituted C-22/C-23 and tetrasubstituted C-34/C-35 double bonds. According to the above described evidence, and since compounds of this type are likely biosynthesized from the same or similar precursors and pathway, the absolute configuration of 1 was proposed as 1S,2S,9R,12S,21S,26S,27R,30R,31S,33S.The relative configuration of reported , NOE corurations . Further2) m/z = 721.4283 indicated the same molecular formula of 2, C41H62O9, as that of 1. The 13C NMR spectrum of 2 showed similar signals to those of 1. Also, it displayed carbon signals of 9 methyls, 11 methylenes, 10 methines, and 11 quaternary carbons. By detailed analysis of the 2D NMR spectral data of 2, a similar gross structure to that of 1 was deduced. However, it was found that 2 possesses a remarkably upfield-shifted signal of H-4 , while 1 displayed a downfield-shifted resonance for H-4 . Also, the 13C NMR spectroscopy data were found to be quite similar to those of 1, with the exception of CH3-19 at δC 26.6 in 1 and δC 20.3 in 2, suggesting the presence of a trans geometry of 4,5-double bond.The pseudomolecular ion peak of sardigitolide B  showed an NOE correlation with H-2 , but not with H3-19 , confirming the E geometry of the double bond at C-4 and C-5 again. These results determined 2 to be the 4E isomer of 1.The relative configurations of the stereogenic centers in 3) exhibited a protonated molecular peak at m/z 721.4281 41H62O9, and 11 degrees of unsaturation as those of 1 and 2. The 13C NMR spectroscopy data also showed 41 carbon signals, including 8 methyl groups, 13 methylene, 9 methines, and 11 quaternary carbons. Analyzing the 2D NMR spectral data of 3 in detail showed a similar gross structure of 3 to that of 1, except that the chemical shifts of CH2-19  in 3 indicated the presence of 1,1-disubstituted double bond at C-5/C-19. The relative configuration of 3 was also determined from NOESY spectrum, which showed similar NOE correlations among the corresponding protons to those of 1. This is the first ximaolide-type compound containing a disubstituted double bond at C-5.Sardigitolide C (4) was isolated as a white amorphous solid. The HR-ESI-MS of 4 showed a pseudomolecular ion peak at 721.4268 41H62O9 and implying 11 degrees of unsaturation. In the 13C and DEPT-135 spectra, 4 showed 41 carbon signals resembling those of 1 including 9 methyls, 11 methylenes, 10 methines, and 11 quaternary carbons. Also, 4 had the same gross structure as 1 according to the detailed analyses of 1D and 2D NMR (COSY and HMBC) spectra. However, it was found that H-33 of 4 showed a different coupling constant (J = 10.5 Hz) to that of H-33 (J = 6.4 Hz) in 1. Furthermore, 4 did not show NOE correlation between H-22  and H-33 , while 1–3 exhibited NOE interactions between H-22 and H-33, revealing the 33R configuration. On the basis of the above findings, the molecular structure of 4 was determined unambiguously to be the 33-epimer of 1.Sardigitolide D  exhibited inhibitory activity toward MCF-7and MDA-MB-231 cells with IC50 values of 9.6 ± 3.0 and 14.8 ± 4.0 μg/mL, respectively, and glacumolide A (6) showed cytotoxicity toward MCF-7, HepG2, and HeLa cell lines with IC50 values of 10.1 ± 3.3, 14.9 ± 3.5, and 17.1 ± 4.5 µg/mL, respectively. Glacumolide B (7) also was found to display cytotoxicity toward MCF-7, MDA-MB-231, and HepG2 cell lines, with IC50 values of 9.4 ± 3.0, 17.8 ± 4.5, and 14.9 ± 4.2 µg/mL, respectively. The monocembranoid 8 (molecular weight 374) showed cytotoxicity against the growth of MCF-7 cancer cell line with IC50 value of 10.9 ± 4.3 µg/mL (29.1 ± 11.4 µM). The remaining compounds did not show any effective cytotoxic and anti-inflammatory activities.It is known that IL-1rthritis ,32, neurrthritis , and carrthritis . Furtherinopathy ,36. In t results  showed t10) (11) has been found to be the dienophile part of this series biscembranoids for only one time [1 and 4 are the Diels–Alder reaction products using -dehydromethyl tortuosoate (12), 2 using -dehydromethyl tortuosoate (13), and 3 using -dehydromethyl tortuosoate (14), respectively, as the dienophiles in the biscembranoids biosynthesis. Cembranoids 12–14 are waiting for discovery in future investigations.Methyl tortuosoate, also called methyl tetrahydrosarcoate (10) , has beeone time . BiscembSarcophyton glacum led to the discovery of two biscembranoid-type compounds, glaucumolide A (6) and glaucumolide B (7) [6, 7, and analogs have been confirmed in 2019 by Wen et al. from the X-ray single crystal diffraction of the same compound 6, isolated from the soft coral S. trocheliophorum [S. glacum contained more than seven genetically distinct clades which might be the reason for the continuous discovery of high chemical diversity of secondary metabolites of the soft coral S. glacum [Sarcophyton genus could generate similar structure biscembranoids as our present study.Our previous investigation of secondary metabolites from the soft coral de B (7) . The abs. glacum . For the1H and 13C, respectively; or on Varian 400 MR FT-NMR instrument at 400 MHz and 100 MHz for 1H and 13C, respectively. The data of low-resolution electron spray ionization mass spectroscopy (LRESIMS) were measured by Bruker APEX II mass spectrometer. The data of HRESIMS were obtained by Bruker Apex-Qe 9.4T mass spectrometer. Silica gel 60 and reverse-phased silica gel  were used for normal-phase and reverse-phased column chromatography. Precoated silica gel plates   were used for analytical TLC. High-performance liquid chromatography was performed on a Hitachi L-2455 HPLC apparatus with a Supelco C18 column .Optical rotations and IR spectra were recorded on a JASCO P-1020 polarimeter and FR/IR-4100 infrared spectrophotometer , respectively. NMR spectra were acquired on a Varian Unity Inova 500 FT-NMR  at 500 and 125 MHz for Sarcophytondigitatum of this study was originally collected from the wild in an 80-ton cultivation tank (height 1.6 m) located in the National Museum of Marine Biology and Aquarium, Taiwan. The tank was designed to simulate the fringing reefs in southern Taiwan [S. digitatum was harvested in the National Museum of Marine Biology & Aquarium, Pingtung, in 2014. The coral was identified by one of the authors of this study (C.-F.D.). The animal sample was stored at the Department of Marine Biotechnology and Marine Resources, National Sun Yat-Sen University.The cultured soft coral n Taiwan . The botn Taiwan . The watS. digitatum (0.9 kg) was sliced and exhaustively extracted with ethyl acetate (1 L × 5), and the solvent-free residue was sequentially partitioned between water and n-hexane, ethyl acetate, and n-butanol to yield three samples from the above solvents. The resulted EtOAc extract (1.098 g) was purified over silica gel by column chromatography and eluted with acetone in n-hexane , and then with methanol in acetone  to yield 13 fractions. Fraction 2 was eluted with the solvent system of acetone–n-hexane (6:1) to obtain 4 subfractions (A–D). Subfraction 2-B was purified by RP-HPLC using MeOH/H2O (3:1) at a flow rate of 5 mL/min to afford 8 (2.1 mg). Fraction 3 was eluted with acetone–n-hexane (1:5) followed by isolation over a silica gel column to yield 5 subfractions (A–E). Subfraction 3-D was also purified by RP-HPLC with the solvent system of MeOH/H2O (4:1) at a flow rate of 5 mL/min to obtain 9 (3.4 mg). Fraction 10 was eluted with acetone–n-hexane (1:3) and rechromatographed over RP-18 gel to obtain 6 subfractions (A–F). Subfraction 10-F was exhaustively purified by RP-HPLC using MeOH/H2O (2:1) at a flow rate of 5 mL/min to yield 6 (20.2 mg) and 7 (13.5 mg). Fraction 11, eluting with acetone–n-hexane (1:2), was carefully isolated by a reverse-phase silica gel column to yield 6 subfractions (A−F). Subfraction 11-C was further purified by RP-HPLC using MeOH/H2O (2:1) at a flow rate of 5 mL/min to obtain 1 (8.6 mg), 2 (4.0 mg), 3 (2.5 mg), 4 (2.0 mg), and 5 (23.3 mg).A sample of 1: white powder; c 1.3, CHCl3), IR (KBr) vmax 3433, 2958, 1705, 1603, 1436, 1373, 1205, 1135, 1061, 1029 cm−1, 13C and 1H NMR data, m/z 721 m/z 721.4287 41H62O9Na, 721.4292)Compound 2: white powder; c 0.1, CHCl3), IR (KBr) vmax 3398, 2927, 1704, 1607, 1372, 1204, 1135, 1070 cm−1, 13C and 1H NMR data, m/z 721 m/z 721.4283 41H62O9Na, 721.4292)Compound 3: white powder; c 0.8, CHCl3), IR (KBr) vmax 3445, 2959, 1703, 1435, 1372, 1206, 1061 cm−1, 13C and 1H NMR data, m/z 721 m/z 721.4281 41H62O9Na, 721.4292)Compound 4: white powder; c 0.5, CHCl3), IR (KBr) vmax 3446, 2957, 2925, 1706, 1603, 1435, 1375, 1206, 1061 cm−1, 13C and 1H NMR data, m/z 721 m/z 721.4268 41H62O9Na, 721.4292)Compound 1–8 in dimethyl sulfoxide (DMSO) for 72 h to screen cytotoxicity. Doxorubicin, the positive control of the MTT assay, showed cytotoxicity towards MCF-7, MDA-MB-231, HepG2, and HeLa cancer cell lines, with IC50 values of, 0.7 ± 0.1, 1.3 ± 0.2, 1.2 ± 0.4, and 0.4 ± 0.1 (µg/mL), respectively.Cell lines were purchased from the American Type Culture Collection . Cytotoxicity assays were carried out using the MTT assays . MCF-7, 4 cells/mL and allowed to grow overnight. The cell cultures were added to the DMSO as control or different concentrations of compounds 1–8, followed by treatment with LPS 1 µg/mL for 24 h. Determination of the cytokine concentration was performed by ELISA according to the manufacturer’s protocol and previously reported method [Murine macrophage cell line J774A.1 was purchased from the American Type Culture Collection . J774A.1 cells were cultured in 96-well plates at a concentration of 5 × 10d method .Sarcophyton digitatum led to the purification of four new biscembranoids 1–4, along with five known compounds 5–9. With regards to biological activities, compounds 2, 6, and 7 displayed inhibitory activities against the proliferation of a limited panel of cancer cell lines in a cytotoxic assay. Furthermore, compounds 6 and 8 showed anti-inflammatory activity, which inhibited LPS-induced enhanced IL-1β production. The soft coral Sarcophyton sp. has been shown to produce various biscembranoid metabolites. Up to date, more than 60 biscembranoids biosynthesized via Diels–Alder reaction were isolated. Interestingly, these biscembranoids and their biosynthetic monocembranoid precursors are often found in Sarcophyton species [Sarcophyton species might produce structurally diversified bioactive compounds that could be beneficial for future drug development. Furthermore, the three dienophiles 12–14 are waiting for discovery as new cembranoids in future studies.Investigation of  species ,44,45,46


R)-6E-tetradecene-8,10,12-triyne-1-ol-5-O-β-glucoside (1), was isolated from the flower of Coreopsis lanceolata (Compositae), together with two known compounds, bidenoside C (10) and -5E-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-β-glucopyranoside (11), which were found in Coreopsis species for the first time. The other known compounds, lanceoletin (2), 3,2′-dihydroxy-4-3′-dimethoxychalcone-4′-glucoside (3), 4-methoxylanceoletin (4), lanceolin (5), leptosidin (6), (2R)-8-methoxybutin (7), luteolin (8) and quercetin (9), were isolated in this study and reported previously from this plant. The structure of 1 was elucidated by analyzing one-dimensional and two-dimensional nuclear magnetic resonance and high resolution-electrospray ionization-mass spectrometry data. All compounds were tested for their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and compounds 2-4, 6 and 7 inhibited DPP-IV activity in a concentration-dependent manner, with IC50 values from 9.6 to 64.9 μM. These results suggest that C. lanceolata flower and its active constituents show potential as therapeutic agents for diseases associated with type 2 diabetes mellitus.A new polyacetylene glycoside, (5 Coreopsis is a perennial plant belonging to the Compositae family D26 –11.5° . CD (MeOH) λmax (Δε) 228 (+0.52), 243 (–0.83), 286 (–0.11), 307 (–0.26) nm. 1H (500 MHz) and 13C (125 MHz) data (CD3OD), see +  ((501.1575) .R)-methoxybutin (7): Yellow powder. [α]D26 –117.9° . CD (MeOH) λmax (Δε) 275 (–0.11), 289 (+0.19), 300 (−0.23) nm.-5E-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-β-glucopyranoside (11): Brown solid. [α]D26 +82.1° . CD (MeOH) λmax (Δε) 226 (−2.50), 253 (+1.33), 290 (+0.67), 309 (+0.78) nm.(350) was determined using GraphPad Prism software  via a dose–response analysis.The measurement of DPP-IV activity was performed using the DPP-IV inhibitor screening assay kit , based on the manufacturer’s protocols . Briefly, a DDP assay buffer consisting of 20 mM Tris-HCL (pH 8.0), 100 nM NaCl and 1 mM EDTA was used for the assay solution. Each of the compounds were initially dissolved in DMSO at a concentration of 1 mM. Subsequently, the final concentration of compounds was diluted to 0.1, 1, 10, 25, 50 and 100 μM, respectively. The human recombinant DPP-IV enzyme and the substrate 5 mM H-Gly-Pro conjugated to aminomethylcoumarin (AMC) were put in the same buffer. Diluted assay buffer (30 μL) and diluted enzyme solution (10 μL) were added to a 96-well plate containing 10 μL of solvent (blank) or 10 μL of solvent-dissolved test compounds. The reaction by adding 50 μL of the diluted solution of the fluorogenic substrate was initiated and cleavage of the peptide bond by DPP released the free AMC group. The fluorescence was measured as an excitation wavelength of 350 nm and an emission wavelength of 450 nm using a plate reader . The percentage inhibition was expressed as [(DPP-IV level of vehicle-treated control−DPP-IV level of test samples)/DPP-IV level of vehicle-treated control] × 100. Subsequently, the 50% inhibitory concentration (ICR)-6E-tetradecene-8,10,12-triyne-1-ol-5-O-β-glucoside (1), was isolated from the C. lanceolata flower, along with 10 known compounds. Other polyacetylene glycosides, bidenoside C (10) and -5E-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-β-glucopyranoside (11), were found in the Coreopsis species for the first time. In the screening for any DPP-IV inhibitory activity of the isolates 1–11, compounds 2–4, 6 and 7 inhibited DPP-IV enzyme activity in a dose-dependent manner. This study provides the first demonstration of the compounds responsible for the DPP-IV inhibitory activity of the C. lanceolata flower. Moreover, lanceoletin (2) exhibited the most DPP- IV inhibitory effect; thus our results suggest that 2 could be considered as a lead compound for the development of agents against DPP-IV activity.A new polyacetylene glycoside, namely (5


N-heterocyclic carbene (NHC)-palladium complexes were found to be efficient nano-reactors for Suzuki-Miyaura cross-coupling reactions of water soluble iodo- and bromoaryl compounds with cyclic triol arylborates at low temperature in water without any organic co-solvent. Combined with an improved one-step synthesis of triol arylborates from boronic acid, this remarkably efficient new tool provided a variety of 4′-arylated phenylalanines and tyrosines in good yields at low catalyst loading with a wide functional group tolerance.Nanoformulated calix[8]arenes functionalized with  The Suzuki-Miyaura reaction has emerged as one of the most powerful tool for C–C bond formation because of its compatibility with a broad range of functional groups giving rise to numerous applications throughout organic chemistry, synthesis of pharmaceutical compounds ,2,3 and H-imidazole. The palladium carbene complexes were next generated with palladium chloride in the presence of potassium carbonate and 3-chloropyridine as extra ligand.The calix  arene-NH2Cl2 to solubilize the catalyst  alanine (3ag) were isolated in good yields by prolonging the reaction time to 16 h. Moreover, when the pH was reduced to 7 and 6 the coupling still took place with only a small reduction of yield (Entries 2 and 3). The latter result may be useful for substrates poorly soluble at basic pH and to conduct reaction with biomolecules at physiological pH arene-NHC-Pd catalyst was synthesized according to the method previously reported octan-1-uide (2a), The general method using phenyl boronic acid gave the title compound 14 in 87% yield. 1H NMR : δ = 7.30 ppm , 6.98–6.88 , 3.57 , 0.47  ppm; 13C NMR : δ = 132.1 , 125.5 , 124.0 , 73.6 3), 34.4 , 16.2  ppm. The C-B was not observed; IR : 3064, 2958, 2843, 1613, 1351, 1207, 1093, 1042, 914, 878, 850, 714; MS (ESI−): m/z (%) = 205.1 (100) [M − K]−, 204.1 (20).Tetra-n-butylammonium 4-methyl-1-phenyl-2,6,7-trioxa-1-borabicyclo-[2.2.2]octan-1-uide (2e), The general method using 1 equivalent of n-Bu4NOH as base provided the tetra-n-butylammonium borate salt 2e octan-1-uide (2f), The general method using 4-methoxyphenyl boronic acid give the title compound −, 234.1 (20).compound  as a whiPotassium 4-methyl-1-(3-nitrophenyl)-2,6,7-trioxa-1-borabicyclo-[2.2.2] octan-1-uide (2h), The general method using 3-nitrophenyl boronic acid gave the title compound −, 249 (20).compound  in 72% yPotassium 4-methyl-1-(o-tolyl)-2,6,7-trioxa-1-borabicyclo-[2.2.2]octan-1-uide (2g), The general method using o-tolylboronic acid gave the title compound −, 218 (20).compound  in 59% yPotassium 1-(furan-2-yl)-4-methyl-2,6,7-trioxa-1-borabicyclo-[2.2.2]octan-1-uide (2i), The general method using 2-furylboronic acid gave the title compound , 194.1 (20).compound  in yieldPotassium 4-methyl-1-(thiophen-3-yl)-2,6,7-trioxa-1-borabicyclo-[2.2.2]octan-1-uide (2j), The general method using 3-thienylboronic acid gave the title compound −, 195.1 (100).compound  in yield−6 mmol; 0.00004 equiv.; 80 µL) and the reaction was mixed and shaken on a thermostated shaker (Biosan TS-100) at 800 rpm at 37 °C. After 3 h, the reaction was frozen in liquid nitrogen and the solution lyophilized. The crude product was taken up in CD3OD and analyzed by 1H-NMR.In an Eppendorf tube, the arylhalide  and the boronic acid/cyclic-triolborate salt  were suspended in phosphate buffer pH 8.0–6.0  and MilliQ Water (370 µL). The suspension of Pd-Calix-NS was added  and the boronic acid  were suspended in phosphate buffer pH 8.0  and water  was added and the reaction was stirred at 37 °C. After 3/16 h, the reaction was frozen in liquid nitrogen and the solution was lyophilized. The crude product was purified by flash chromatography on silica gels to afford the expected cross-coupling product.4-Phenylbenzoic Acid (3e), The general method using 4-iodobenzoic acid and potassium phenyltriolborate gave 4-phenylbenzoic acid −.oic acid  (Yield =4-Phenylphenol (3f), The general method using 4-iodophenol and potassium phenyltriolborate gave 4-phenylphenol −.ylphenol  (Yield =2-Phenylbenzoic Acid (3h), The general method using 2-iodobenzoic acid and potassium phenyltriolborate gave 2-phenylbenzoic acid +.laniline  (Yield =2-Phenylaniline (3j), The general method using 2-iodooaniline and potassium phenyltriolborate gave 2-phenylaniline +.laniline  , The general method using N-Boc-4-iodo-l-phenylalanine and potassium phenyltriolborate (2a) gave the title compound −, 266.2 (80) [M-t-BuOH-H]−.compound  in 87% yN-boc-3-phenyltyrosine (3d), The general method using N-Boc-4-iodo-l-tyrosine and potassium phenyltriolborate (2a) gave the title compound −, 282.2 (65) [M-t-BuOH-H]−.compound  in 68% yl-phenylalanineN-Boc-4-(4-methoxyphenyl)- (3af), The general method using N-Boc-4-iodo-l-phenylalanine and potassium 4-methoxy-1-phenyl-2,6,7-trioxa-1-borabicyclo[2.2.2]octan-1-uide (2f) gave the title compound octan-1-uide (2g) gave the title compound −, 280.2 (85) [M-t-BuOH-H]−.compound  in 79% yN-boc-4-(3-nitrophenyl) phenylalanine (3ah), The general method using N-Boc-4-iodo-l-phenylalanine and potassium 3-nitro-1-phenyl-2,6,7-trioxa-1-borabicyclo[2.2.2]octan-1-uide (2h) gave the title compound −, 311.2 (65) [M-t-BuOH-H]−.compound  in 72% yN-boc-4-(2-furanyl) phenylalanine (3ai), The general method using N-Boc-4-iodo-l-phenylalanine and potassium 4-methyl-1-(furan-2-yl)-2,6,7-trioxa-1-borabicyclo[2.2.2]octan-1-uide (2i) gave the title compound in 87% yield 1H NMR : δ = 7.60 , 7.51 , 7.25 , 6.70 , 6.50 , 4.45–4.25 , 3.16 , 2.92 , 1.39 3); 13C NMR : δ = 175.3 , 157.7 , 155.2 , 143.2 (CH), 137.8 (C), 130.7 , 129.8 (C), 124.7 , 112.6 , 105.7 , 80.5 ), 56.2 , 38.5 , 28.6 3); MS m/z (%) (ESI−): 330.2 (100) [M − H]−, 256.2 (85) [M-tBuOH-H]−.N-boc-4-(4-thienyl) phenylalanine (3aj), The general method using N-Boc-4-iodo-l-phenylalanine and potassium 4-methyl-1-(thiophen-3-yl)-2,6,7-trioxa-1-borabicyclo[2.2.2]octan-1-uide (2j) gave the title compound −, 272.1 (50) [M-t-BuOH-H]−.compound  in 63% yTo conclude, we have shown that the nanoformulation of benzyloxycalix  arene suThe high catalytic activity of the Pd-Calix-NS can be attributed to the specific characteristics of the nanostructure exalting the high catalytic power the NHC-Pd structure previously observed in organic solvents ,49. The


M. tuberculosis) strains  equal to the activity of the basic antitubercular drug rifampicin; spiropyrazoline benzoates exhibit an average antitubercular activity of 10–100 μg/mL on MTB strains. Molecular docking studies revealed a series of M. tuberculosis receptors with the energies of ligand–receptor complexes  close to the value of intermolecular pairwise interactions of the same cation in the crystal of spiropyrazolylammonium chloride . However, only in complex with transcriptional repressor EthR2, both stereoisomers of the cation realize similar intermolecular interactions.The analysis of stability of biologically active compounds requires an accurate determination of their structure. We have found that 5-aryl-3-(2-aminoethyl)-1,2,4-oxadiazoles are generally unstable in the presence of acids and bases and are rearranged into the salts of spiropyrazolinium compounds. Hence, there is a significant probability that it is the rearranged products that should be attributed to biological activity and not the primarily screened 5-aryl-3-(2-aminoethyl)-1,2,4-oxadiazoles. A series of the 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium (spiropyrazoline) benzoates and chloride was synthesized by Boulton–Katritzky rearrangement of 5-substituted phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles and characterized using FT-IR and NMR spectroscopy and X-ray diffraction. Spiropyrazolylammonium chloride demonstrates in vitro antitubercular activity on DS (drug-sensitive) and MDR (multidrug-resistant) of MTB ( A number of previously unknown spiropyrazolinium salts were obtained and characterized using FT-IR and NMR spectroscopy and X-ray diffraction. In vitro antitubercular screening of spiropyrazoline benzoates and chloride was carried out, and their molecular docking was performed. It was shown that the hydrolysis of 1,2,4-oxadiazoles with a 3-morpholinoethyl substituent leads to spiropyrazoline compounds within 25–40 h. Acid hydrolysis of 1,2,4-oxadiazoles occurs immediately after reagents adding. In vitro antitubercular screening of benzoates and chloride of spiropyrazoline drug-susceptible and multidrug-resistant strains, M. tuberculosis revealed compounds with significant activity, and the results are in accordance with molecular docking studies.Herein we report on the stability of 5-aryl-3-[β-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles towards hydrolysis at:  were obtained by heating of О-aroyl-(β-morpholin-1-yl)propioamidoximes (3a–e) in DMF at 70 °C for several hours, evaporating off the solvent in an oil pump vacuum and treating of the residue with acetone. 1,2,4-Oxadiazoles (4a–e) are obtained as crystalline precipitates from acetone (The synthesis of the starting compounds  earlier . 5-Subst acetone .4a–e) were recorded immediately after isolation from DMF, and they correspond to the structure of 1,2,4-oxadiazoles. However, the X-ray diffraction analysis of single crystals grown for nine months from 1,2,4-oxadiazoles 4c–е recrystallized from 2-PrOH showed a complete transition of 1,2,4-oxadiazoles into rearranged spiropyrazolinium compounds 5c–е  under the deliberate establishment of hydrolysis conditions: (i) DMF with the two equivalent amount of water when heated to 60–70 °C; (ii) alcohol/ethereal HCl mixture in the presence of air moisture ethyl]-1,2,4-oxadiazoles . Spiropyrazolinium compounds 5а–е were obtained after evaporation of DMF in an oil pump vacuum, treatment of the residue with acetone with the isolation of rearranged products 5а–е and their recrystallization from 2-PrOH. In the case of the action of ethereal HCl solution on alcohol solutions of 1,2,4-oxadiazoles 4a–e in all cases, 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium chloride (6) and the corresponding benzoic acids were isolated.As can be seen from 5a–e and 6 differ from the IR spectra of 1,2,4-oxadiazoles 4a–e. First, the former compounds have symmetric and asymmetric ν(N–H) stretching bands at 3152–3485 and 3158–3457 cm−1, respectively; second, there are pronounced bands of asymmetric and symmetric stretching vibrations of strong intensity ν(СОО–) at 1545–1557 cm−1 and 1420–1442 cm−1, respectively for 5a–e and no stretching bonds of aromatic protons for salt 6.IR spectra view of spirocompounds 1H-NMR spectra of 1,2,4-oxadiazole 4a–e were recorded immediately with isolation; if they were recorded after 1–2 weeks, then the emergence and increase in the intensity of the NH2 group signal of the rearranged spiropyrazolinium products 5a–e in the region of δ 7.51–7.7.57 ppm was observed. It indicates a transition of 1,2,4-oxadiazole to the spiropyrazolinium compounds 4a–e→5a–e in the presence of air moisture.The 1H and 13C) of compounds 4a–e and 5a–e shows almost no differences in the regional characteristics of the groups of protons and carbon atoms of the structures of 5-substituted phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles (4a–e) and of 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium benzoates (5a–e). Hence, protons of α-СH2 and β-СH2 groups in the first case give signals in the range δ 3.15–3.17 ppm and δ 3.65–3.66 ppm and in the region δ 3.15–3.19 ppm and δ 3.64–3.66 ppm—in the second. The signals of the aromatic protons of para-substituted 1,2,4-oxadiazoles 4a, 4b, 4d and spiropyrazolinium benzoates 5a, 5b, 5d have the form of two symmetric doublets with the spin–spin coupling constant J equal 7.5 and 8.0 Hz. Aromatic protons of 1,2,4-oxadiazoles and spiropyrazolinium benzoates with unsubstituted and meta-substituted phenyl rings have signals at δ 7.23–7.83 ppm (4c) and 7.22–7.80 ppm (4e) and 7.25–7.78 ppm . Proton-containing substituents CH3O and CH3 have singlet signals with an intensity of 3 protons at δ 3.73 and 2.27 ppm for compounds 4a, 4b and 5a, 5b.Comparison of the NMR spectra (CH2)2(CH2)2О and N(+)(CH2)2(CH2)2О groups at δ 3.40 and 3.92 ppm, respectively; no aromatic proton signals were observed.The 1H-NMR spectra of compounds 4a–e, 5a–e, and 6, is that the axial and equatorial protons of the methylene groups located at the nitrogen atom of the morpholine ring give independent multiplet signals. In one case, these signals are superimposed with the common signal of two groups methylene protons located at the oxygen atom of the morpholine ring at δ 3.91–3.93 ppm with a total intensity of six protons and in the other case have a multiplet signal at ~δ 3.40 ppm intensity of two protons. The diastereotopicity of discussed geminal protons of compounds 4a–e, 5a–e, and 6 is associated with a dynamic cause due to slow rotation of the morpholine heterocycle. The effect of hindered inversion of six-membered heterocycles, with a chair-like conformer with fixed positions of the axial and equatorial protons being predominant, in the 1H-NMR spectra is a known fact reported in reference data dec-1-en-5-ium salts, X-ray diffraction studies and molecular docking studies were carried out.5c–e and 6 are given in 5c, 5e and 6 contain one water molecule besides the target ions, and the asymmetric unit of 5d contains two cations and two symmetrically independent anions. All hydrogen atoms could be located on residual density maps; thus, it was confirmed that the structures are salts with deprotonated carboxylic acids. The six-membered oxo-containing cycles adopt the chair conformation, and the five-membered aza-containing cycles realize the envelope conformation. C(1) carbon atom deviates from the meanplane of N1=N2-C3-C2 atoms at 0.40(1)–0.49(1) Å. Although the cation is rather rigid, it can realize two conformational isomers depending on the shift of the C(1) atom from the meanplane of the rest atoms of the five-membered ring. In crystals of 5c, 5e and 6, these isomers are related with each other by an inversion center, and in acentric crystal 5d, two symmetrically independent cations realize different conformations -4,5-dihydro-1H-pyrazol-1-ium dec-1-ene-5-ammonium emulates the pterin moiety, known as a precursor of tetrahydrofolate synthesis, a coenzyme that acts as a carrier for one-carbon units in the biosynthesis of thymidylate, purine nucleotides, and some amino acids dec-2-en-8-yl derivatives. These receptors were taken as targets for molecular docking calculations together with more typical for theoretical antitubercular screening UDP-galactopyranose mutase.As we mentioned above, the cation has a rigid conformation with spirocyclic motifs known to be present in some drugs ,28. Thusno acids . ReceptoFor all cases, both stereoisomers of the cation were docked independently. Docking without constraints does not give any ligand: receptor complexes; thus, docking was performed with H-bond constraints similar to that in the initial ligand–receptor complexes. Sterical clashes in the binding pocket of thymidylate synthase and UDP-galactopyranose mutase  do not allow the cation to realize appropriate H-bonding; thus, these receptors were excluded from consideration. For 1NBU and 4XT4, we succeeded in overcoming some steric clashes when flexible residues were allowed to rotate freely along with single bonds. Energies of interactions between the cations and three receptors are listed in 6  estimated using UNI potentials -1,2,4-oxadiazole (4a). Starting from  of 3a in 25 mL of dry DMF to the resulting 2.89 g (62%), colorless solid 4a, m.p. 230 °C, Rf 0.71. IR : 1670 (C=N), 1597 (C=N), 1553 (C=C), 1362 (C–O). 1H-NMR : 3.17 , 3.40  and 3.93 , 3.65 , 3.73 , 6.75 , 7.75 . 13C-NMR : 31.4, 55.4, 62.0, 62.4, 112.5, 130.9, 136.0, 160.0, 168.9, 169.3. Anal. Calcd for C15H19N3O3 : C, 62.27; H, 6.62. Found: C, 62.60; H, 7.02.55-(4-Tolyl)-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazole (4b). Starting from  of 3a in 15 mL of dry DMF to the resulting 1.84 g (70%), colorless solid 4b, m.p. 220 °C, Rf 0.62. IR : 1648 (C=N), 1593 (C=N), 1553 (C=C), 1376 (C–O). 1H-NMR :2.27 , 3.15 , 3.40  and 3.91 , 3.66 , 7.01 , 7.70 . 13C-NMR : 21.3, 31.4, 62.1, 62.4, 63.2, 112.5, 130.9, 136.0, 160.0, 169.0, 169.3. Anal. Calcd for C15H19N3O2 : C, 65.91; H, 7.01. Found: C, 65.50; H 7.22.5-Phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazole (4c). Starting from  of 3с in 5 mL of dry DMF to the resulting 0.86 g (92%) colorless solid 4c, m.p. 216 °C, Rf 0.66. IR : 1650 (C=N), 1596 (C=N), 1559 (C=C), 1381 (C–O). 1H-NMR : 3.18 , 3.40  and 3.93 , 3.65 , 7.23–7.83 . 13C-NMR : 31.4, 62.1, 62.4, 63.3, 127.5, 127.8, 128.9, 129.1, 129.4, 167.0, 169.2. Anal. Calcd for C14H17N3O2 :C, 64.85; H, 6.61. Found: C, 65.30; H, 7.02.5-(4-Bromophenyl)-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazole (4d). Starting from  of 3d in 8 mL of dry DMF to the resulting 1.12 g (83%) colorless solid 4d, m.p. 224 °C, Rf 0.67. IR : 1650 (C=N), 1596 (C=N), 1559 (C=C), 1381 (C–O). 1H-NMR : 3.17 , 3.39  and 3.93 , 3.65 , 7.40 , 7.74 . 13C-NMR : 31.4, 62.1, 62.4, 63.3, 122.7, 130.2, 131.6, 141.5, 168.3, 169.5. Anal. Calcd for C14H16BrN3O2 (338.20): C, 49.72; H, 4.77. Found,%: C, 49.29; H, 4.97.5-(3-Chlorophenyl)-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazole (4e). Starting from  of 3e in 15 mL of dry DMF to the resulting 1.43 g (56%) colorless solid 4e, m.p. 190 °C, Rf0.62. IR : 1680 (C=N), 1596 (C=N), 1557 (C=C), 1377 (C–O). 1H-NMR : 3.15 , 3.40  and 3.91 , 3.65 , 7.25–7.78 . 13C-NMR : 31.4, 62.1, 62.4, 63.2, 127.7, 127.8, 129.2, 132.4, 144.5, 162.1, 169.2. Anal. Calcd for C14H16ClN3O2 (293.75): C, 57.24; H, 5.49. Found,%: C, 57.55; H, 5.92.4a–e) in DMF in a ratio of 0.5 g: 10 mL, respectively, two equivalents of H2O was added dropwise. The reaction solutions were heated at 70 °C with TLC control during the time typical for groups of compounds 4a–e: 4a, b (40 h), 4c–e (25 h).After the disappearance of the 1,2,4-oxadiazoles 4a–e spots on the silufol plate and the appearance of products 5a–e spots, the solvent was evaporated to dryness in an oil vacuum pump. Acetone was added to the viscous residues of the reaction mixtures 5a–e at the rate of 0.5 g of the starting compounds 4a–e: 15 mL of acetone. The formed precipitates of 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-ene-5-ammonium 3,4-substituted benzoates (5a–e) were filtered off and dried at room temperature.To the solutions of 5--3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles . Starting from 0.5 g (0.0017 mol) of compound 4a in 10 mL of DMF and 0.062 mL (0.0034 mol) H2O to the resulting 0.35 g (63%) colorless solid 5a, m.p. 235 °C, Rf 0.75. IR : 1657 (C=N), 1594 (C=C), 1548 (νCOO– as), and 1420 (νCOO– sy), 3309, 3414, 3459 [νN(-H)2]. 1H-NMR : 2.27 , 3.17 , 3.41  and 3.92 , 3.65 , 6.78 , 7.55 and 7.60 , 7.78 . 13C-NMR : 31.4, 62.4, 63.2, 112.5, 130.9, 134.8, 159.9, 144.5, 168.8, 169.2. Anal. Calcd for C15H23N3O5 : C, 55.37; H, 7.13. Found,%: C, 55.79; H, 7.57.2-Amino-8-oxa-1,5-diazaspiro[4.5]dec-1-ene-5-ammonium 4-methylbenzoate hydrate (5b). Starting from 0.5 g (0.0018 mol) of the compound 4b in 10 mL of DMF and 0.066 mL (0.0036 mol) H2O to the resulting 0.35 g (63%) colorless solid 5b, m.p. 248 °C, Rf 0.80. IR : 1655 (C=N), 1597 (C=C), 1550 (COO–as), and 1442 (COO– sy), 3157, 3312, 3457 [N(-H)2]. 1H-NMR : 3.15 , 3.41  and 3.93 , 3.64 , 3.73 , 7.02 , 7.54 , 7.69 . 13C-NMR : 21.3, 31.38, 62.1, 62.4, 63.2, 127.9, 128.3, 129.4, 139.7, 168.8, 169.2. Anal. Calcd for C15H23N3O4. : C, 58.24; H, 7.49. Found: C, 58.29; H, 7.59.2-Amino-8-oxa-1,5-diazaspiro[4.5]dec-1-ene-5-ammonium benzoate hydrate (5c). Starting from 0.5 g (0.0019 mol) of 4c in 10 mL of DMF and 0.07 mL (0.0038 mol) H2O to the resulting 0.43 g (77%) colorless solid 5c, m.p. 220 °C, Rf 0.75. IR :1658 (C=N), 1596 (C=C), 1556 (COO– as), and 1426 (COO– sy), 3152, 3311, 3456 [N(-H)2]. 1H-NMR : 3.19 , 3.39  and 3.93 , 3.65 , 7.22–7.80 , 7.55 and 7.64 . 13C-NMR : 31.4, 61.3, 62.4, 63.2, 127.26, 128.3, 129.4, 142.4, 168.7, 169.2. Anal. Calcd for C14H21N3O4 : C, 56.94; H, 7.17. Found: C, 56.79; H, 7.50.2-Amino-8-oxa-1,5-diazaspiro[4.5]dec-1-ene-5-ammonium 4-bromobenzoate (5d). Starting from 0.5 g (0.0015 mol) of 4d in 10 mL of DMF and 0.05 mL (0.0028 mol) H2O to the resulting 0.43 g (80%) colorless solid 5d, m.p. 240 °C, Rf 0.77. IR : 1657 (C=N), 1591 (C=C), 1545 (COO– as), and 1423 (COO–sy), 3302, 3411, 3485 [N(-H)2]. 1H-NMR : 3.15 , 3.40  and 3.92 , 3.65 , 7.39 , 7.55 , 7.73 . 13C-NMR : 31.4, 62.1, 62.4, 63.2, 121.9, 130.1, 131.6, 141.8, 167.4, 169.2. Anal. Calcd for C14H18BrN3O3 : C, 47.20; H, 5.09. Found: C, 47.49; H, 4.97.2-Amino-8-oxa-1,5-diazaspiro[4.5]dec-1-ene-5-ammonium 3-chlorobenzoate hydrate (5e). Starting from 0.5 g (0.0017 mol) 4e in 10 mL of DMF and 0.06 mL (0.034 mol) H2O to the resulting 0.24 g (43%) colorless solid 5e, m.p. 200 °C, Rf 0.70. IR : 1657 (C=N), 1594 (C=C), 1557 (COO– as), and 1420 (COO– sy), 3155, 3309, 3457 [N(-H)2]. 1H-NMR : 3.16 , 3.40  and 3.93 , 3.66 , 7.25–7.78 , 7.57 and 7.61 . 13C-NMR : 31.4, 62.1, 62.5, 63.2, 127.9, 128.2, 129.2, 129.3, 132.4, 144.7, 167.0, 169.2. Anal. Calcd for C14H20ClN3O4 : C, 50.99; H, 6.11. Found: C, 50.52; H, 6.47.4a–e) in 10 mL ethanol a HCl solution in ether was added dropwise to pH 2. A white precipitate of 2-amino-1,5-diazaspiro[4.5]dec-1-en-5-ium chloride hydrate (6) in all cases was formed at once in 75–82% yields and collected by filtration. 3,4-Substituted benzoic acids were precipitated during the evaporation of mother liquors obtained after the filtration of chloride monohydrate 6. All characteristics of substituted benzoic acids corresponded to the reference data.To a solution of 0.2 g (0.0007 mol) of 5--3-[2-(morpholin-1-yl)ethyl]- 1,2,4-oxadiazoles —white opaque powder, m.p. 257–260 °C, Rf 0.21. IR : 1639 (νC=N), , 1362 (νC–O), 3158, 3310, 3457 [νN(-H)2]. 1H-NMR : 3.16 , 3.40  and 3.92 , 3.68 , 7.51 . 13C-NMR spectrum, δ, ppm: 31.4, 31,5, 62.1, 62.4, 63.3, 169.2. Anal. Calcd for C7H16N3O2 (209.67): C, 40.10, H 7.69. Found: C, 40.29; H, 7.97.5c–e, 6 were collected at 120 K on a Bruker Apex II diffractometer  equipped with an Oxford Cryostream cooling unit and a graphite monochromated Mo anode (λ = 0.71073 Å). Crystal structures were solved using SHELXT dec-1-en-5-ium chloride. 3D molecular structure of the cation extracted from crystal structure was used for molecular docking studies with various M. tuberculosis receptors. It was demonstrated that two stereoisomers of the rigid cation form different sets of hydrogen bonds in complexes with dihydroneopterin aldolase or oxidoreductase Rv2671 and similar H-bonds in complex with thymidylate synthase. However, energies of all ligand–receptor complexes vary from −35.8 to −42.8 kcal/mol.5-Substituted phenyl-3-(2-aminoethyl)-1,2,4-oxadiazoles in the presence of moisture and acids undergo Boulton–Katritsky rearrangement to the salts of spiropyrazolinium compounds—2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium benzoates and chloride. Hence, biological screening results should be associated with rearranged products and not with the original taken on trials 5-substituted phenyl-3-(2-aminoethyl)-1,2,4-oxadiazoles. A small library of the newly 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium benzoates and chloride has been used in the drug design of antitubercular drugs. The tested compounds show moderate to high in vitro antitubercular activity with MIC values of 1–100 µg/mL. The highest activity in 1 µg/mL and 2 µg/mL on DS and MDR of


All of the series monomers present enantiotropic smectic H and smectic G phase and the series polymers show enantiotropic smectic A phase which three polymers contained exhibit smectic E. Polyoxetanes have been used as a cationic ring-opening polymerization of oxetane monomers bearing a pendant trans-stilbene mesogenic unit including different spacer length and terminal alkyl length.A series of fourteen liquid crystalline monomers and polyoxetanes containing trans-biphenyl side group have been successfully synthesized. The thermal and mesomorphic properties of monomers ( The first thermotropic side-chain liquid crystalline polymers were synthesized by Finkelmann and Rehage ,2. They In the past few decades, a large number of side-chain liquid crystal polymers had been synthesized ,9,10. ThAccording to the experimental results, polyoxetane flexibility had more than polyacrylate and polymethacrylate. The polymerization of the side-chain liquid crystalline polyoxetane molecular weight distribution (MWD) is less than 1.3.The purpose of this research is to show the synthesis of a new series of side-chain liquid crystalline polyoxetanes containing the trans-stilbene mesogenic side group. The effects of terminal alkyl length and spacer length on the properties of mesophases exhibited are discussed.1H-NMR (400 MHz) spectra were measured using a Bruker AM 400 instrument . The thermal transitions and the anisotropic textures were measured using a Carl-Ziess Axiphot polarized optical microscope  and a Mettler FP82 hot stage . Differential scanning calorimeter (DSC) was recorded on a Seiko SSC/5200  with determined compounds of thermal transitions and thermodynamic parameters equipped with a cooling accessory. Thermal stability was measured using a Seiko TG/DTA 200 thermal gravimetric analyzer . X-ray diffraction by liquid crystals was measured using a Riraku powder diffractometer .1H-NMR spectroscopy were verified as the chemical structures and purity of the intermediates and target compounds. The synthesis methods and analysis of each product are described below.The intermediates and targets compound synthetic routes were represented in 1a)3-[(3-Bromopropoxy)methyl]-3-methyloxetane (1b)3-[(4-Bromobutoxy)methyl]-3-methyloxetane (1c)3-[(5-Bromopentoxy)methyl]-3-methyloxetane (1d)3-[(6-Bromohexoxy)methyl]-3-methyloxetane (1e)3-[(12-Bromododecoxy)methyl]-3-methyloxetane : 1.30 , 1.46–1.90 4CH2–), 3.39–3.48 4CH2Br), 4.34, 4.51 .3-(Hydroxymethyl)-3-methyloxetane , dibromohexane , and hexane (120 mL) was added to a stirred solution of sodium hydroxide  in 150 mL of water. Then, tetrabutylammonium bromide (1.0 g) was added to the solution. The solution was stirred for 12 h at room temperature, then heated to reflux for 0.5 h. The reaction solution cooled to room temperature, 1000 mL of water was added, and the organic layer was extracted three times with hexane. The extraction solution was dried through anhydrous magnesium sulfate and after removal of the solvent under reduced pressure. The crude product was purified by distillation, to yield 20.85 g (80.3%) of a colorless transparent liquid. 2a)3-[[3-propoxy]methyl]-3-methyl oxetane (2b)3-[[4-butoxy]methyl]-3-methyl oxetane (2c)3-[[5-pentoxy]methyl]-3-methyl oxetane (2d)3-[[6-hexoxy]methyl]-3-methyl oxetane (2e)3-[[12-dodecanoxy]methyl]-3-methyl oxetane (3a)4-Butoxy-benzaldehyde (3b)4-Pentoxy-benzaldehyde (3c)4-Hexoxy-benzaldehyde (3d)4-Heptoxy-benzaldehyde (3e)4-Octoxy-benzaldehyde  was added dropwise after the solution mentioned above was refluxed for 1 h. The solution refluxed for 12 h and then cooled to room temperature. The solution was extracted with water and ethyl acetate. The extraction solution was washed with 10% KOH solution three times and dried through anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the crude product was purified by column chromatography on silica gel using ethyl acetate/hexane as eluent to yield 2.42 g (82.5%) of light yellow liquid. 1H-NMR : 1.30 , 1.40–1.82 4CH2–), 3.46 , 4.04 , 4.33, 4.49 , 6.96 , 7.81 , 9.87 .4-Hydroxybenzaldehyde  was added to a stirred solution of potassium hydroxide  and potassium iodide (0.2 g) in 100 mL of 95% ethanol. Compound 4a)4-Butoxy-benzyl alcohol (4b)4-Pentoxy-benzyl alcohol (4c)4-Hexoxy-benzyl alcohol (4d)4-Heptoxy-benzyl alcohol (4e)4-Octoxy-benzyl alcohol : 0.89 , 1.31–1.80 4CH3), 3.96 4–), 4.66 , 6.89 , 7.30 .A solution of sodium tetrahydridoborate  in 2 mL of 0.45 N sodium hydroxide with 28 mL water was slowly added dropwise to 4-Hexoxy-benzaldehyde  with methanol (150 mL) solution. The solution was stirred 3 h at room temperature. Remove most of the methanol by distillation. The solution was extracted with ether and aqueous of dilute acid solution (50 mL). The organic phase was washed with 2% aqueous of sodium bicarbonate, saturated aqueous of sodium chloride, and dried through anhydrous magnesium sulfate. The crude product was purified by column chromatography on silica gel using n-hexane/ethyl acetate as eluent to yield 13.8 g (92.1%) of colorless liquid. 5a)4-Butoxy-benzyl chloride (5b)4-Pentoxy-benzyl chloride (5c)4-Hexoxy-benzyl chloride (5d)4-Heptoxy-benzyl chloride (5e)4-Octoxy-benzyl chloride : 0.89 , 1.31–1.80 4CH3), 3.96 4–), 4.66 , 6.89 , 7.30 .4-Hexoxy-benzyl alcohol  was reacted with excess thionyl chloride  in 50 mL of methylene chloride. The solution was stirred at ice bath for 6 h. Then, added with water (30 mL) into the solution. The organic phase was washed with 10% aqueous of sodium bicarbonate, saturated aqueous of sodium chloride, and dried through anhydrous magnesium sulfate. The crude product was purified by column chromatography on silica gel using n-hexane/ethyl acetate as eluent to yield 4.58 g (84.3%) of light-yellow liquid. 6a)Diethyl[(4-butoxy)benzyl]phosphonate (6b)Diethyl[(4-pentoxy)benzyl]phosphonate (6c)Diethyl[(4-hexoxy)benzyl]phosphonate (6d)Diethyl[(4-heptoxy)benzyl]phosphonate (6e)Diethyl[(4-octoxy)benzyl]phosphonate : 0.89 , 1.22 2, 1.31–1.79 4CH3), 3.05 , 3.93–4.01 4– and P(OCH2CH3)2), 6.89 , 7.30 .4-Hexoxy-benzyl chloride  was injected by triethyl phosphite  with a syringe under nitrogen. The reaction mixture was refluxed for 12 h, then, was purified by distillation under reduced pressure to yield 5.89 g (81.6%) of colorless liquid. 1M)3-[3-(Trans-4′-methoxystilben-4-yloxy)propoxymethyl]-3-methyl oxetane (2M)3-[4-(Trans-4′-methoxystilben-4-yloxy)butoxymethyl]-3-methyl oxetane (3M)3-[5-(Trans-4′-methoxystilben-4-yloxy)pentoxymethyl]-3-methyl oxetane (4M)3-[6-(Trans-4′-methoxystilben-4-yloxy)hexoxymethyl]-3-methyl oxetane (5M)3-[6-(Trans-4′-butoxystilben-4-yloxy)hexoxymethyl]-3-methyl oxetane (6M)3-[6-(Trans-4′-pentoxystilben-4-yloxy)hexoxymethyl]-3-methyl oxetane (7M)3-[6-(Trans-4′-hexoxystilben-4-yloxy)hexoxymethyl]-3-methyl oxetane (8M)3-[6-(Trans-4′-heptoxystilben-4-yloxy)hexoxymethyl]-3-methyl oxetane (9M)3-[6-(Trans-4′-octoxystilben-4-yloxy)hexoxymethyl]-3-methyl oxetane (10M)3-[12-(Trans-4′-butoxystilben-4-yloxy)dodecoxymethyl]-3-methyl oxetane (11M)3-[12-(Trans-4′-pentoxystilben-4-yloxy)dodecoxymethyl]-3-methyl oxetane (12M)3-[12-(Trans-4′-hexoxystilben-4-yloxy)dodecoxymethyl]-3-methyl oxetane (13M)3-[12-(Trans-4′-heptoxystilben-4-yloxy)dodecoxymethyl]-3-methyl oxetane (14M)3-[12-(Trans-4′-octoxystilben-4-yloxy)dodecoxymethyl]-3-methyl oxetane  and compound 6d  was added dropwise to a stirred mixture. The reaction mixture was stirred for 12 h at room temperature. The reaction solution mixture was poured into ice water. The solution was filtered, the remaining yellow solid was recrystallized from dimethyl formamide to yield 1.62 g of light-yellow solid.Sodium hydride  dissolved in dry THF (50 mL) on the brown flask, 13-crown-5-ether (30 mg) was added to react under nitrogen in the ice bath. Then, a solution of compound lH-NMR spectrometer, the product yield, and element analysis of monomers 1M~14M were as follows.The 1M: Yield: 40.7%; 1H-NMR : 1.28 , 2.03 , 3.48 3–), 3.62 , 3.80 , 4.04 , 4.32, 4.48 , 6.84, 7.38 ; element analysis: Calc. for C23H28O4: C 75.00, H 7.61, O 17.39; found C 75.00, H 7.75, O 17.25%.Compound 2M: Yield: 38.6%; 1H-NMR : 1.31 , 1.79 2–), 3.49 , 3.82 , 3.98 , 4.34, 4.50 , 6.85, 7.39 ; element analysis: Calc. for C24H30O4: C 75.39, H 7.85, O 16.75; found C 75.46, H 7.99, O 16.45%.Compound 3M: Yield: 33.4%; 1H-NMR : 1.34 , 1.58–1.87 3–), 3.51 , 3.85 , 3.99 , 4.38, 4.53 , 6.85, 7.43 ; element analysis: Calc. for C25H32O4: C 75.76, H 8.08, O 16.16; found C 75.52, H 8.15, O 16.33%.Compound 4M: Yield: 30.8%; 1H-NMR : 1.31 , 1.47–1.85 4–), 3.46 , 3.81 , 3.99 , 4.34, 4.50 , 6.87, 7.26 ; element analysis: Calc. for C26H34O4: C 76.10, H 8.29, O 15.61; found C 75.82, H 8.47, O 15.71%.Compound 5M: Yield: 40.6%; 1H-NMR : 0.96 , 1.31 , 1.47–1.80 2CH3; –OCH2(CH2)4CH2–), 3.46 , 3.94 , 4.35, 4.51 , 6.86, 7.39 ; element analysis: Calc. for C29H40O4: C 76.99, H 8.85, O 14.16; found C 77.03, H 9.02, O 13.95%.Compound 6M: Yield: 36.7%; 1H-NMR : 0.91 , 1.31 , 1.41–1.79 3CH3; –OCH2(CH2)4CH2–), 3.45 , 3.94 , 4.35, 4.50 , 6.86, 7.39 ; element analysis: Calc. for C30H42O4: C 77.25, H 9.01, O 13.73; found C 77.21, H 9.15, O 13.64%.Compound 7M: Yield: 41.0%; 1H-NMR : 0.91 , 1.31–1.80 4CH3, –OCH2(CH2)4CH2–), 3.46 , 3.94 , 4.35, 4.50 , 6.86, 7.39 ; element analysis: Calc. for C31H44O4: C 77.50, H 9.17, O 13.33; found C 77.47, H 9.26, O 13.27%.Compound 8M: Yield: 40.6%; 1H-NMR : 0.88 , 1.26–1.80 5CH3, –OCH2(CH2)4CH2–), 3.46 , 3.95 , 4.35, 4.50 , 6.86, 7.39 ; element analysis: Calc. for C32H46O4: C 77.73, H 9.31, O 12.96; found C 77.60, H 9.40, O 13.00%.Compound 9M: Yield: 38.6%; 1H-NMR : 0.87 , 1.26–1.82 6CH3, –OCH2(CH2)4CH2–), 3.46 , 3.94 , 4.35, 4.50 , 6.86, 7.39 ; element analysis: Calc. for C33H48O4: C 77.95, H 9.45, O 12.60; found C 77.92, H 9.54, O 12.54%.Compound 10M: Yield: 34.7%; 1H-NMR : 0.96 , 1.29–1.79 2CH3, –OCH2(CH2)10CH2–), 3.43 , 3.96 , 4.35, 4.50 , 6.86, 7.39 ; element analysis: Calc. for C35H52O4: C 78.36, H 9.70, O 11.94; found C 78.22, H 9.80, O 11.98%.Compound 11M: Yield: 39.1%; 1H-NMR : 0.91 , 1.27–1.78 3CH3, –OCH2(CH2)10CH2–), 3.43 , 3.94 , 4.34, 4.50 , 6.86, 7.39 ; element analysis: Calc. for C36H54O4: C 78.54, H 9.82, O 11.64; found C 78.26, H 9.90, O 11.84%.Compound 12M: Yield: 24.1%; 1H-NMR : 0.90 , 1.26–1.79 4CH3, –OCH2(CH2)10CH2–), 3.43 , 3.94 , 4.34, 4.50 , 6.86, 7.39 ; element analysis: Calc. for C37H56O4: C 78.72, H 9.93, O 11.35; found C 78.40, H 10.05, O 11.55%.Compound 13M: Yield: 27.4%; 1H-NMR : 0.87 , 1.26–1.77 5CH3, –OCH2(CH2)10CH2–), 3.44 , 3.95 , 4.35, 4.49 , 6.85, 7.38 ; element analysis: Calc. for C38H58O4: C 78.90, H 10.03, O 11.07; found C 78.73, H 10.11, O 11.16%.Compound 14M: Yield: 34.7%; 1H-NMR : 0.89 , 1.29–1.81 6CH3, –OCH2(CH2)10CH2–), 3.46 , 3.94 , 4.35, 4.50 , 6.86, 7.39 ; element analysis: Calc. for C39H60O4: C 79.05, H 10.14, O 10.81; found C 78.92, H 10.20, O 10.88%.Compound 1H-NMR and GPC.In this study, all the polymers were synthesized by cationic ring-opening polymerization. The preparation of polymer is described below. Under nitrogen, dichloromethane was dried by calcium hydride and was distilled just prior to use. Boron trifluoride ether complex (freshly distilled) was used as an initiator. Under nitrogen, a solution of monomer (0.5 mmol) and dichloromethane (5 mL) was cooled to 0 °C and the initiator of 2% mol with respect to monomer was injected with a syringe. The reaction solution mixture was stirred at 0 °C for 24 h. Then, the resulting polymers were precipitated in methanol and purified further by dissolving in dichloromethane and then precipitating in ethanol repeatedly. The absence of monomer was checked by This study intends to explore the liquid crystalline monomers of oxetane and liquid crystalline polyoxetane. Among the compounds of these monomers and polymers, spacer length and terminal chain length have influences on the thermal properties and mesophase. The molecular structure and the general synthetic procedures of the series of monomers are shown in 1M~14M) in this series, and their structures are exhibited in Monomers are composed of trans-stilbene as a mesogenic unit, their spacers length include several different alkyl chains  and links with the terminals of different alkoxyl length . Moreover, there are fourteen monomers (1M~14M) used BF3. OEt2 as an initiator to carry out the ring-opening polymerization and successfully synthesized a series of brand-new side-chain liquid crystalline polymers (1P~14P), and their structures and their synthesis procedures are listed in All monomers (1M~14M) and polymers (1P~14P) are measured using DSC, POM, and X-ray. The phase transition temperature and enthalpy changed of monomers 1M~14M are reported in 1M~14M) reveal enantiotropic smectic H and smectic G phases.The thermal and mesomorphic properties of monomers . As can be seen from 5M is 2.6 °C, 6M is 3.3 °C, 7M is 2.1 °C, 8M is 20.6 °C, 9M is 38.1 °C). In addition, when the length of the terminal groups become shorter, the transition temperature of liquid crystalline will gradually overlap with the isotropic temperature. 5M~7M are observed by POM, only the tiny transition of liquid crystalline phases can be seen. There is a tendency for the isotropic temperature to lower down the temperature from 136.4 to 118.0 °C when the length of terminal alkoxy is changed from m = 4 to m = 8. 10M~14M (containing twelve methylene units spacer length) finds that the length of terminal alkoxy becomes larger, and the mesogenic temperature range becomes smaller . This is the opposite result as compared with that of monomers 5M~9M. This result may be due to the flexible spacer with a too larger length. From the above result, it is found that the mesomorphic temperature range has a great relationship with the spacer length. 9M for an example, the dendritic growth pattern is developed at the temperature of 116.1 °C during the cooling scanning process, then mosaic platelets  that contain a short flexible spacer (n = 3~6) and only one methyl terminal group show smectic A phase. Polymers  have different length of alkoxy terminal groups (m = 4~8). Their isotropic temperature and liquid crystalline transition temperature exhibits the same tendency. The isotropic temperature of 5P and 10P (m = 4) is especially high, maybe four alkoxy terminal groups can be easily arranged. 6P~9P and 11P~14P (m = 5~8) polymers increase in isotropic temperature with the length of the alkoxy terminal group. 11P~14P more than 6P~10P formed the regular liquid crystalline phase because they have a long flexible spacer.1P~14P) cannot be solved in an organic solvent  under room temperature. During the ring-opening polymerization, the stilbene group might be cross-linked, because the total amount of H was decreased from the NMR spectrum after the polymerization, which might also cause the poor solubility of the synthesized polymer. In this study, 7P and 14P were selected for measuring molecular weight under the higher temperature of GPC, in which the solvent of m-cresol was used, and the test temperature of 85 °C was set. The molecular weight of 7P is Mn = 4031, Mw = 5107, DPI = 1.266. The molecular weight of 14P is Mn = 3666, Mw = 5052, DPI = 1.378. The results are presented as a ring-polymerization reaction by BF3. OEt2, the molecular weight of the obtained polymer is not high, but its dpi is small, as expected. The structure of the polymers is comb-like, and polystyrene was used as the standard of GPC, the test results from using GPC would be lower. However, in fact, the molecule weight should be higher.The synthesized polymers (14M shows HS and GS, 14P shows AS and ES, and has a relatively stable liquid crystal phase.In this study, a series of fourteen liquid crystalline monomers and polyoxetanes containing trans-biphenyl side group are successfully synthesized. It is known from the results that the liquid crystal phase transition temperature, the isotropic temperature, the stability of the liquid crystal phase, and the type of the liquid crystal all have a great influence on both the length of the soft spacer and the length of the terminal alkyl group. It is found that the difference in the length of the soft spacer and the length of the terminal alkyl group affect the monomer or polymer. When the length of the soft spacer and the length of the terminal alkyl group are increased, the liquid crystal phase formed is polymorphism of mesophases, such as


Z)-1,1,1-trichloro-4-alkyl(aryl)amino-4-arylbut-3-en-2-ones  and 2,2-difluoro-3-alkyl(aryl)amino-4-aryl-6-(trichloromethyl)-2H-1,3,2-oxazaborinin-3-ium-2-uides  in which 3(4)-alkyl(aryl) = H, Me, iso-propyl, n-butyl, C6H5, 4-CH3C6H4, 4-CH3OC6H4, 4-NO2C6H4, 4-FC6H4, 4-BrC6H4, 2-naphthyl, is reported. A series of β-enaminoketones  is synthesized from the O,N-exchange reaction of some amines (3) with (Z)-1,1,1-trichloro-4-methoxy-4-aryl-but-3-en-2-ones  at 61–90% yields. Subsequently, reactions of the resulting β-enaminoketones with an appropriate source of boron (BF3.OEt2) gave the corresponding oxazaborinine derivatives  at 50–91% yields. UV-Vis and emission properties of biomolecule-binding properties for the DNA of these new BF2-β-enamino containing CCl3 units were also evaluated. Some compounds from the present series also exhibited potent antimicrobial effects on various pathogenic microorganisms at concentrations below those that showed cytotoxic effects. Compounds 4d, 4e, 6e, and 6f showed the best results and are very significant against P. zopfii, which causes diseases in humans and animals.The synthesis, antimicrobial activity evaluations, biomolecule-binding properties (DNA), and absorption and emission properties of a new series of ( Unsaturated heterocyclic compounds containing a boron atom have increased interest in recent years as a result of their potential in basic research and applications . Stands Indeed, these properties promote the use of these structures in several applications such as, light emitting diodes  and solaRecently, our research group developed several difluoro-organoboron analogues. Nitrogenated heterocyclic scaffolds such as pyridines, . pyrimidOn the other hand, β-enaminoketones are the isosteric analogues of 1,3-enolic ketones and have been used in recent years as N,O double-dentate ligands to form 1,3,2-oxazaborines. These difluoroboron complexes of β-enaminones, which belong to the family of β-iminoenolate boron complexes , have at3.Et2O)  .On the other hand, β-enaminoketones are interesting and easy obtainable synthetic intermediary. Enaminoketones have received attention due to their ambident nucleophilicity characteristics of amines, else with the ambident electrophilicity of enones .β-enaminoketones and β-enaminoketo-esters are synthesized through the condensation reactions between carbonyl compounds and primary or secondary amines acid-catalysed . Due to β-enaminones they have been also used to prepare different important antibacterial, . anti-inMoreover, trihalomethyl groups in heterocyclic structures may drastically amend their chemicals, physical and pharmacological characteristics. The construction of trihalomethylated structures is done through already halogenated building blocks . TrihaloQuinine isolated from chinchona bark led successive and innovative class of antimalarials  substituents with electron-donating or electron-withdrawing effect at the 3-position and a phenyl group at the 4-position. Furthermore, in view of the biological potential of molecules containing trihalomethyl groups, the aim of this paper was also to report the antimicrobial screening and cytotoxicity analysis of the compounds synthetized here  equipped with a 5-mm PABBO probe, 5-mm sample tubes at 298 K, and digital resolution of 0.01 ppm, in CDCl3, and using CFCl3 and BF3·OEt2, respectively, as the external reference. All spectra can be found at the Unless otherwise indicated, all common reagents and solvents were used as obtained from commercial suppliers and without further purification. δ), multiplicity, integration, and coupling constant (Hz). The following abbreviations were used to explain multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, and dd = double doublet. All NMR chemical shifts were reported in parts per million and relative to the internal reference.All results were reported with the chemical shift .via direct infusion of the sample (flow: 10 µl min-1) in positive-ion mode using electrospray ionization. Elemental composition calculations for comparison were executed using the specific tool included in the Qual Browser module of Xcalibur  software. The spectra can be found in the High resolution mass spectra (HRMS) were obtained for all compounds in an LTQ Orbitrap Discovery mass spectrometer (Thermo Fisher Scientific). This hybrid system combines the LTQ XL linear ion trap mass spectrometer and an Orbitrap mass analyzer. Experiments were performed 4g and 6e was measured using a Bruker D8 QUEST diffractometer using Cu Ka radiation (l = 1.54080 Å) with a KAPPA four-circle goniometer equipped with a PHOTON II CPAD area detector. Absorption corrections were performed using the multi-scan method. Anisotropic displacement parameters for non-hydrogen atoms were applied. Most hydrogen atom positions were calculated geometrically and refined using the riding model, although some hydrogen atoms were refined freely. The structure was solved and refined using the WinGX software package , methanol (MeOH), and dimethyl sulfoxide (DMSO) as solvents and concentration solution at 10–5 M range. Steady-state emission fluorescence analysis of samples in the same solvents used in absorption analysis were measured with a Varian Cary 50 fluorescence spectrophotometer . Due to the absence of emission intensity of all derivatives in all solvents, it was not possible to determine fluorescence quantum yield values.-4 M range). The DNA pair base concentrations of low molecular weight DNA from calf thymus (CT-DNA) were determined by UV-vis absorption spectroscopy using ϵ = 6.600 M−1cm−1 (per base pair) at λmax = 260 nm. Derivatives solutions in DMSO with Tris-HCl were titrated with increasing concentrations of CT-DNA (ranging from 0 to 100 μM). The absorption spectra of the compounds were acquired in the wavelength range of 250–700 nm. The binding constants (Kb) of derivatives were calculated according to the decay of the absorption bands of compounds using Equation 1 through a plot of [DNA]/(ϵa − ϵf) versus [DNA],For DNA interactions, boron complexes titrations with calf-thymus DNA (CT-DNA) were performed by UV-vis analysis at room temperature in DMSO (2%)-Tris-HCl buffer mixture (pH 7.2) using DMSO stock solution of derivatives (10a is the extinction coefficient (Aobs/[compound]), and ϵb and ϵf are the extinction coefficients of free and fully bound forms, respectively. In the plots of [DNA]/(ϵa − ϵf) versus [DNA], Kb is given by the ratio of the slope for the interception.where [DNA] is the concentration of DNA in the base pairs, ϵ-7 M) and DNA (1.0 × 10-5 M) in a Tris-HCl pH 7.4 buffer solution. Derivative concentration ranged from 0 to 100 µM. All samples were excited at λexc = 510 nm and emission fluorescence spectra were recorded at the range of 550–800 nm, 5 min after each addition of the complex solution in order to allow incubation to occur (incubation time). The fluorescence quenching Stern-Volmer constants (KSV) of compounds were calculated according to the decay of the emission bands of EB-DNA using Equation 2 through a plot of F0/F versus [DNA],Competitive EB-binding studies were performed using steady-state emission fluorescence assay with CT-DNA. Compounds were dissolved in DMSO and through the gradual addition of the stock solution of the boron complexes to the quartz cuvette (1.0 cm path length) containing ethidium bromide dye   .b) using Equation 3:The standard Gibbs free energy (ΔG°) of derivative-DNA complex was calculated from the values of binding constant (KZ)-1,1,1-trichloro-4-methoxy-4-phenylbut-3-en-2-one (1) (5 mmol) in ethanol (20 ml), the respective amines   were added and the resulting mixtures were refluxed for 24 h. After that, the solutions were cooled at –10°C, resulting in yellow or white solids. The solids were filtered under atmospheric pressure, washed with cold ethanol, and dried under reduced pressure.To magnetically stirred solutions of  δ: 10.65 , 7.50–7.45 , 7.38–7.36 , 5.68 , 3.77–3.65 , 1.23 , 1.21 . 13C NMR  δ: 180.5 (C-2), 169.1 (C-4), 134.9 (Ph), 130.0 (Ph), 128.7 (Ph), 127.1 (Ph), 97.2 (CCl3), 87.3 (C-3), 46.8 (CH), 23.9 (CH3). MS , m/z (%) = 305 , 270 (1), 242 (9), 188 (100), 146 (19), 103 (14), 77 (7). Anal. Cal. for C13H14Cl3NO (306.62): C, 50.92; H, 4.60; N, 4.57. Found: C, 50.89; H, 4.40; N, 4.59.Physical aspect: brown oil. Yield: 90%.1H NMR  δ: 10.74 , 7.49–7.45 , 7.39–7.36 , 5.75 , 3.26 , 1.57 , 1.37 , 0.88 . 13C NMR  δ: 180.6 (C-2), 170.2 (C-4), 134.6 (Ph), 130.1 (Ph), 128.7 (Ph), 127.4 (Ph), 97.2 (CCl3), 87.4 (C-3), 45.0 (CH2), 32.3 (CH2), 19.8 (CH2), 13.5 (CH3). MS , m/z (%) = 319 , 256 (7), 202 (100), 184 (6), 103 (9). Anal. Cal. for C14H16Cl3NO (320.64): C, 52.44; H, 5.03; N, 4.37. Found: C, 52.46; H, 5.03; N, 4.44.Physical aspect: yellow solid. Yield: 76%. Melting point: 123–124°C.1H NMR  δ: 12.02 , 7.41–7.39 , 7.36–7.33 , 7.16 , 7.07 , 6.81 , 6.04 . 13C NMR  δ: 181.7 (C-2), 165.7 (C-4), 138.3 (Ph), 134.6 (Ph), 130.4 (Ph), 128.9 (Ph), 128.7 (Ph), 128.4 (Ph), 125.5 (Ph), 123.7 (Ph), 96.9 (CCl3), 90.9 (C-3). MS , m/z (%) = 339 , 269 (12), 222 (100), 180 (5), 77 (16). HRMS (ESI-TOF): C16H12Cl3NO (M + H), requires 340.0057. Found 340.0069.Physical aspect: yellow solid. Yield: 85%. Melting point: 112–113°C.1H NMR  δ: 12.04 , 7.42–7.32 , 6.95 , 6.70 , 6.02 , 2.25 . 13C NMR  δ: 181.5 (C-2), 165.8 (C-4), 135.6 (Ph), 135.4 (Ph), 134.7 (Ph), 130.3 (Ph), 129.5 (Ph), 128.6 (Ph), 128.4 (Ph), 123.6 (Ph), 97.0 (CCl3), 90.4 (C-3), 20.8 (CH3). MS , m/z (%) = 353 , 319 (1), 236 (100), 91 (6). HRMS (ESI-TOF): C17H14Cl3NO (M + H), requires 354.0214. Found 354.0226.Physical aspect: yellow solid. Yield: 88%. Melting point: 144–145°C.1H NMR  δ: 12.06 , 7.41–7.32 , 6.76 , 6.69 , 6.68 , 3.73 . 13C NMR  δ: 181.5 (C-2), 166.0 (C-4), 157.5 (Ph), 134.7 (Ph), 131.2 (Ph), 130.3 (Ph), 128.6 (Ph), 128.4 (Ph), 125.3 (Ph), 114.2 (Ph), 97.0 (CCl3), 90.0 (C-3), 55.4 (CH3). MS , m/z (%) = 369 , 334 (2), 252 (100), 209 (26). HRMS (ESI-TOF): C17H14Cl3NO2 (M + H), requires 370.0163. Found 370.0173.Physical aspect: yellow solid. Yield: 65%. Melting point: 107–109°C.1H NMR  δ: 11.83 , 8.03 , 7.53–7.49 , 7.44–7.37 , 6.85 , 6.16 . 13C NMR  δ: 182.6 (C-2), 163.8 (C-4), 144.4 (Ph), 144.0 (Ph), 133.9 (Ph), 131.2 (Ph), 129.3 (Ph), 128.2 (Ph), 124.8 (Ph), 122.4 (Ph), 96.5 (CCl3), 94.1 (C-3). Anal. Cal. for C16H11Cl3N2O3 (385.63): C, 49.83; H, 2.88; N, 7.26. Found: C, 49.78; H, 2.85; N, 7.26.Physical aspect: solid beige. Yield: 87%. Melting point: 115–116°C.1H NMR  δ: 11.95 , 7.42–7.30 , 6.88–6.77 , 6.04 . 13C NMR  δ: 181.9 (C-2), 165.8 (C-4), 160.3 , 134.4 , 134.4 (Ph), 130.5 (Ph), 128.8 (Ph), 128.4 (Ph), 125.5 , 115.9 , 96.9 (CCl3), 90.8 (C-3). MS , m/z (%) = 358 , 294 (4), 269 (13), 240 (100), 198 (4), 95 (8). HRMS (ESI-TOF): C16H11Cl3FNO (M + H), requires 357.9963. Found 357.9976.Physical aspect: yellow solid. Yield: 80%. Melting point: 142–144°C.1H NMR  δ: 11.92 , 7.46–7.42 , 7.39–7.32 , 7.28 , 6.67 , 6.06 . 13C NMR  δ: 181.9 (C-2), 165.2 (C-4), 137.4 (Ph), 134.1 (Ph), 132.0 (Ph), 130.7 (Ph), 128.9 (Ph), 128.3 (Ph), 125.0 (Ph), 118.7 (Ph), 96.7 (CCl3), 91.5 (C-3).m/z (%) = 418 , 301 , 301 , 302 , 269 (27), 271 (7), 234 (14), 221 (51), 193 (41), 192 (7), 165 (14), 102 (15), 76 (16). HRMS (ESI-TOF): C16H11BrCl3NO (M + H), C, 45.81; H, 2.64; N, 3.34. Found: C, 45.53; H, 2.54; N, 3.27.MS , Physical aspect: yellow solid. Yield: 85%. Melting point: 149–151°C.1H NMR  δ: 12.39, 8.28 , 7.85 , 7.62 , 7.55 , 7.34–7.20 , 7.12 , 6.71 , 6.19 . 13C NMR  δ: 182.1 (C-2), 167.1 (C-4), 134.7 (Ph), 134.3 (Ph), 134.0 (Ph), 130.3 (Ph), 128.6 (Ph), 128.4 (Ph), 128.0 (Ph), 127.2 (Ph), 126.7 (Ph), 126.5 (Ph), 124.9 (Ph), 123.2 (Ph), 121.9 (Ph), 96.9 (CCl3), 91.2 (C-3). MS , m/z (%) = 391 , 355 (2), 290 (3), 272 (100), 273 (21), 244 (9), 166 (4), 127 (14), 77 (5). HRMS (ESI-TOF): C20H14Cl3NO (M + H), requires 390.0217. Found 390.0214.Physical aspect: yellow solid. Yield: 80%. Melting point: 115–116°C.1H NMR  δ: 13.11 , 7.14 , 7.05 , 6.66 , 6.61 , 3.70 , 2.34 , 1.95 . 13C NMR  δ: 179.7 (C-2), 168.2 (C-4), 156.9 (Ph), 139.1 (Ph), 131.9 (Ph), 131.3 (Ph), 129.3 (Ph), 128.6 (Ph), 125.4 (Ph), 113.9 (Ph), 98.8 (CCl3), 94.8 (C-3), 55.3 (OCH3), 21.3 (CH3), 16.8 (CH3). Anal. Cal. for C19H18Cl3NO2 (385.63): C, 57.24; H, 4.55; N, 3.51. Found: C, 57.18; H, 4.57; N, 3.51.Z)-1,1,1-trichloro-4-alkyl(aryl)amino-4-phenylbut-3-en-2-ones  (1 mmol) were dissolved in anhydrous CHCl3 (15 ml), followed by the addition of BF3·OEt2 (1 ml of 48% ether sol.) and anhydrous Et3N (1 ml). The mixtures were stirred at temperature of reflux for 18 h, then diluted with CHCl3, washed with water (3× 20 ml) and the organic phase was dried with Na2SO4, filtered, and then the solvent (CHCl3) was removed under reduced pressure. The resulting oils were solubilized in EtOH (15 ml) at ambient temperature and stored overnight in the freezer for precipitation of the products 6a-i and 7e. The resulting solids were filtered under reduced pressure and washed with cold ethanol. The pure products 6 and 7 were obtained at 50–91% yields.In 50 ml round bottom flasks equipped with reflux condenser and drying tube, the respective  δ: 7.59–7.57 , 7.34–7.32 , 6.23 , 4.19–4.14 , 1.44 , 1.42 . 13C NMR  δ: 172.30 (C-4), 165.39 (C-6), 134.20 (C-4’1), 130.79 (C-4’4), 129.41 (C-4’2), 125.74 (C-4’3), 96.86 (C-5), 91.70 (CCl3), 54.20 (CH), 21.83 (CH3). 11B NMR  δ: 1.24 . 19F NMR  δ: −134.64 – −134.99 (m). Anal. Cal. For C13H13BCl3F2NO (354.42): C, 44.06; H, 3.70; N, 3.95. Found: C, 44.08; H, 3.85; N, 4.02.Physical aspect: brown solid. Yield: 80%. Melting point: 85–86°C.1H NMR  δ: 7.60–7.55 , 7.38–7.36 , 6.29 , 3.58 , 1.73 , 1.19 , 0.79 . 13C NMR  δ: 172.7 (C-4), 165.7 (C-6), 133.3 (C-4’1), 131.1 (C-4’4), 129.3 (C-4’2), 126.3 (C-4’3), 96.4 (C-5), 91.8 (CCl3), 48.8 (NCH2), 32.3 (CH2), 20.1 (CH2), 13.4 (CH3). 11B NMR  δ: 1.13 . 19F NMR  δ: −138.13 – −138.36 (m). Anal. Cal. For C14H15BCl3F2NO (368.44): C, 45.64; H, 4.10; N, 3.80. Found: C, 46.16; H, 3.84; N, 3.93.Physical aspect: yellow solid. Yield: 65%. Melting point: 198–199°C.1H NMR  δ: 7.41–7.14 , 6.60 . 13C NMR : 172.3 (C-4), 167.9 (C-6), 139.6 (C-3’1), 133.5 (C-4’1), 131.5 (C-4’4), 129.0 (C-4’2),128.7 (Ph), 128.6 (Ph), 128.2 (Ph), 126.4 (Ph), 96.3 (C-5), 91.8 (CCl3). 11B NMR  δ: 1.34 . 19F NMR  δ: −132.97 – −134.25 (m). Anal. Cal. For C16H11BCl3F2NO (388.43): C, 49.47; H, 2.85; N, 3.61. Found: C, 49.41; H, 2.96; N, 3.61.Physical aspect: yellow solid. Yield: 70%. Melting point: 173–175°C.1H NMR  δ: 7.39 , 7.31 , 7.23 , 7.04 , 6.58 , 2.28 . 13C NMR  δ: 172.0 (C-4), 167.7 (C-6), 138.3 (C-3’1), 137.1 (C-3’4), 133.7 (C-4’1), 131.4 (C-4’4), 129.6 (C-4’2), 128.7 (Ph), 128.6 (Ph), 126.1 (C-4’3), 96.3 (C-5), 91.9 (CCl3), 21.0 (CH3). 11B NMR  δ: 1.31 . 19F NMR  δ: −133.84 – −133.90 (m). Anal. Cal. For C17H13BCl3F2NO (402.46): C, 50.73; H, 3.26; N, 3.48. Found: C, 50.57; H, 3.32; N, 3.52.Physical aspect: yellow solid. Yield: 91%. Melting point: 152–153°C.1H NMR  δ: 7.42–7.38 , 7.35–7.30 , 7.25–7.22 , 7.06 , 6.76 , 6.58 , 3.75 . 13C NMR  δ: 171.8 (C-4), 167.5 (C-6), 159.1 (C-3’4), 133.7 (C-4’1), 132.4 (C-3’1), 131.3 (C-4’4), 128.8 (C-4’2), 128.6 (C-3’2), 127.4 (C-4’3), 114.2 (C-3’3), 96.3 (C-5), 91.8 (CCl3), 55.4 (OCH3). 11B NMR  δ: 1.29 . 19F NMR  δ: −131.70 – −136.45 (m). Anal. Cal. For C17H13BCl3F2NO2 (418.46): C, 48.79; H, 3.13; N, 3.35. Found: C, 48.64; H, 3.22; N, 3.24.Physical aspect: yellow solid. Yield: 60%. Melting point: 201–202°C.1H NMR  δ: 8.13 , 7.48–7.43 , 7.38–7.33 , 7.23 , 6.66 . 13C NMR  δ: 173.6 (C-4), 169.7 (C-6), 147.1 (C-3’1), 145.3 (C-3’4), 132.9 (C-4’1), 132.3 (C-4’4), 129.3 (C-4’3), 128.6 (C-3’2), 127.8 (C-4’2), 124.4 (C-3’3), 96.5 (C-5), 91.6 (CCl3). 11B NMR  δ: 1.30. 19F NMR  δ −132.18 – −132.59 (m). Anal. Cal. For C16H10BCl3F2N2O3 (433.43); C, 44.34; H, 2.33; N, 6.46. Found: C, 44.33; H, 2.20; N, 6.38.Physical aspect: yellow solid. Yield: 67%. Melting point: 169–170°C.1H NMR  δ: 7.45–7.40 , 7.36–7.32 , 7.23–7.21 , 7.15–7.12 , 6.99–6.94 , 6.60 13C NMR  δ: 172.7 (C-4), 168.1 (C-6), 161.9 , 135.6 , 133.3 (C-4’1), 131.6 (C-4’4), 128.9 (C-4’2), 128.5 (C-4’3), 128.2 , 116.1 , 96.3 (C-5), 91.7 (CCl3). 11B NMR  δ: 1.28 . 19F NMR  δ: −112.39 (s); −133,37 – −133,43 (m). Anal. Cal. For C16H10BCl3F3NO (406.42): C, 47.28; H, 2.48; N, 3.45. Found: C, 46.97; H, 2.30; N, 3.59.Physical aspect: yellow solid. Yield: 50%. Melting point: 174–175°C.1H NMR  δ: 7.46–7.33 , 7.23 , 7.03 , 6.61 . 13C NMR  δ: 172.6 (C-4), 168.4 (C-6), 138.7 (C-3’1), 133.2 (C-4’1), 132.3 (C-4’4), 131.8 (C-3’4), 129.0 (C-4’2), 128.6 (C-4’3), 128.0 (C-3’2), 122.3 (C-3’3), 94.7 (C-5), 91.7 (CCl3). 11B NMR  δ 1.25 . 19F NMR  δ: −133.21 (s). Anal. Cal. For C16H10BBrCl3F2NO (467.33): C, 41.12; H, 2.16; N, 3.00. Found; C, 41.29; H, 2.00; N, 3.05.Physical aspect: yellow solid. Yield: 74%. Melting point: 197–198°C.1H NMR  δ: 7.77–7.74 , 7.49–7.37 , 7.21–7.17 , 7.10–7.06 , 6.69 . 13C NMR  δ: 174.9 (C-4), 168.5 (C-6), 135.9 (Ph), 133.8 (Ph), 133.5 (Ph), 131.4 (Ph), 129.0 (Ph), 128.6 (Ph), 128.3 (Ph), 128.2 (Ph), 127.4 (Ph), 127.2 (Ph), 126.5 (Ph), 125.0 (Ph), 124.7 (Ph), 122.8 (Ph), 96.2 (C-5), 91.9 (CCl3). 11B NMR  δ: 1.75–1.16 (m). 19F NMR  δ: −132.66 – −137.64 (m). Anal. Cal. For C20H13BCl3F2NO (438.49): C, 54.78; H, 2.99; N, 3.19. Found; C, 54.72; H, 3.17; N, 3.31.Physical aspect: yellow solid. Yield: 69%. Melting point: 171–173°C.1H NMR  δ: 7.10 , 6.95–6.91 , 6.69 , 3.72 , 2.30 , 1.96 . 13C NMR  δ: 177.0 (C-4), 164.1 (C-6), 158.7 (C-3’4), 140.3 (C-3’1), 133.0 (C-4’1), 130.0 (C-4’4), 129.3 (C-4’2), 127.9 (C-4’3), 127.2 (C-3’2), 113.9 (C-3’3), 103.4 (C-5), 94.0 (CCl3), 55.3 , 21.3 . 16.7 (CH3). 11B NMR  δ: 0.66 – 0.53 (m). 19F NMR  δ: −138.63 – −138.74 (m). Anal. Cal. For C19H17BCl3F2NO2 (446.51): C, 51.11; H, 3.84; N, 3.14. Found; C, 51.11, H, 3.87, N, 3.12.Z)-1,1,1-trichloro-4-methoxy-4-phenylbut-3-en-2-one (1) and (Z)-1,1,1-trichloro-4-methoxy-3-methyl-4-(p-tolyl)but-3-en-2-one (2) were synthetized according to the methodology reported by our group in previous works. Compounds 1 and 2 were synthesized in two steps from reactions of acetophenone or propiophenone using an excess amount of trimethyl orthoformate. Finally, the acylation reaction of the dimethyl acetal intermediates with trichloroacetyl chloride conducted to the compounds 1 and 2 -1,1,1-trichloro-4-alkyl(aryl)amino)-4-phenylbut-3-en-2-ones (4a-e and 5e), the methodology described in the literature was employed because the O,N-exchange reaction was already well established by our research group. In the present work, we reacted (Z)-1,1,1-trichloro-4-methoxy-4-phenylbut-3-en-2-one (1) (5 mmol) and several amines (3a-i) (7.5 mmol) at a molar ratio of 1:1.5, in ethanol (20 ml) for 24 h at reflux temperature . are alp-tolylamino)but-3-en-2-one (4d) was employed to evaluate the influence of different reaction conditions such as solvent, temperature, time, and volume of BF3.OEt2 or Et3N to obtain the oxazaboron complexes 6, 7 -1,1,1-trichloro-4-phenyl-4-, and 4 ml of Et3N (~28 mmol) at room temperature, but this attempt did not lead to product formation after 24–48 h , although the result was only 46% yield  was with 1 mmol of β-enaminoketone, 1 ml of Et3N (~7 mmol), and 1 ml of BF3.OEt2 (~4 mmol) in 15 ml of anhydrous CHCl3 under reflux for 18 h -1,1,1-trichloro-4-alkyl(aryl)amino-4-phenylbut-3-en-2-ones (4a-i and 5e) in order to expand the structural diversity of the corresponding boron complexes 6a-i, 7e (Z)-1,1,1-trichloro-4-alkyl(aryl)amino-4-phenylbut-3-en-2-ones (4a-i and 5e) were submitted to target BF2-coordination, where the alkyl and aryl derivatives furnished the desired products 6a-i and 7e in moderate to excellent yields (50–91%).After the reaction optimization, we investigate the substrate scope of  and N-butyl 6b (80%), which were isolated in good yields, were also successfully included in the reaction scope. Similar conditions were also found for 4-substituted aryl-amines, including aniline 6c (65%) and 2-naphthylamine 6i (58%). Electron-donating 4-methylphenylamino and 4-methoxyphenylamino substituents from anilines 3d and 3e performed very well with this procedure and the desired complexes 6d and 6e were obtained in 70 and 91% yields, respectively. Electron-withdrawing groups, such as 4-nitrophenylamino from aniline 3f, also afforded the respective coordination complex 6f in 60% yield. 4-phenylhalogenated β-enaminoketones were also submitted to the target BF2-coordination. Thus, derivatives of 4-fluoro- and 4-bromo-substituted anilines presented good reactivities and allowed also the isolation of complexes 6g (67%) and 6h (50%).Furthermore, 4-9c to study its reactivity against BF3.OEt2 (9c was synthesized using the methodology described using (Z)-1,1,1-trifluoro-4-methoxy-4-phenylbut-3-en-2-one (8) with aniline (3c). The compound 9c was obtained after recrystallization in 85% yield.In view of the differentiated properties that the trifluoromethyl substituent confers in various molecules in both chemical materials and medicinal chemistry, we also synthesized an example of substituted trifluoromethyl β-enaminoketone 9c against BF2.OEt2 complexation, the optimized reaction condition carried out for the (Z)-1,1,1-trichloro-4-alkyl(aryl)amino-4-phenylbut-3-en-2-ones (4a-i and 5e) was attempted for 9c. However, the formation of trifluoromethylated complex 10c was not possible because the high electron-withdrawing effect of the trifluoromethyl group at position 6, which hinders a stable N-B-O coordination.In order to investigate the synthetic reactivity of trifluoromethyl β-enaminoketone 4a-i, 5e, 6a-i, and 7e were confirmed and characterized by 1H-, 13C-, 11B-, and 19F-NMR spectroscopy, CHN elemental analysis or high-resolution mass spectra (HRMS).The new structures of 4a-i, 5e were deduced on the basis of the NMR data of other β-enaminones previously synthesized in literature.50,51 The 1H NMR chemical shifts of the β-enaminoketone hydrogens (NH) for 4a-i, 5e showed chemical shifts at an average of 11.87 ppm, which suggests to us that the compounds 4a-i, 5e are in the Z,Z-conﬁguration in solution (CDCl3), which is favored by an hydrogen interaction (N–H···OC). The vinyl hydrogen (H-3) was observed in the form of a singlet at an average of 6.06 ppm for all compounds 4, 5. The 13C NMR spectra of all compounds 4a-i and 5e showed, on average, chemical shifts at 181.4 ppm C-2, 166.7 ppm for C-4, 90.8 ppm for C-3, and 97.1 ppm for CCl3.The structures of compounds 1H-NMR data of compounds 4a-i, 5e and 6a-i, 7e showed clearly that complexes 6a-i and 7e do not show chemical shift signals (N–H) around at 12 ppm. Furthermore, an alteration in the chemical shifts of the H-3 signals from 6.06 ppm in average for the β-enaminones 4, 5 to 6.53 ppm in the boron complexes 6, 7 was also observed.A comparison between the 13C NMR data of the β-enaminone precursors 4a-i, 5e and the boron complexes 6a-i, 7e, the major evidence for the formation of 6a-i, 7e was the alteration in the chemical shifts at average of the carbons C-4, C-6, CCl3, and C-5 for 173.1, 167.3, 96.9, and 92.0 ppm, respectively.Upon comparing the 19F- and 11B-NMR experiments were also performed. 19F-NMR spectra of compounds 6a-i, 7e were performed using chloroform-d and, the signals were observed in the form of a multiplet for the compounds in the range of -131.7 ppm to -138.7 ppm. For the 11B-NMR spectra, the chemical shifts were observed in the form of a triplet at 1.26 ppm on average for each compound due to the coupling of both 19F nuclei. However, for compounds 6a-i and 7e, the 19F-NMR spectra showed a multiplet for each compound at -134.1ppm and -135.59 ppm, respectively.Moreover, in order to demonstrate boron complex formation, 4a-i, 5e, 6a-i, and 7e was determined and confirmed by single-crystal X-ray diffraction of the representative β-enaminone 4g and the boron complex 6e  → S0(π) in nature. Yoshii et al. also reported and attributed the same nature transition in their compounds, although the authors measured in THF solution  theoretical calculations were performed for compounds of series 6a-i and 7e using the Gaussian 09 package of programs  was studied by UV-Vis at 250–600 nm region using DMSO (2%)/Tris-HCl pH 7.2 buffer mixture solution. The effect of different concentrations of CT-DNA on the UV-Vis spectra of derivative 6a is presented in 2-derivatives absorption spectra are shown in In the present study, the interaction of the boron complexes 2 moiety with the nucleobase residues of the DNA . A slight bathochromic shift in some cases was also observed, indicating a weak or non-electrostatic interaction observed between the cited compounds and CT-DNA (terature .b) data for the BF2-compounds were listed in b values are associated to the BF2-DNA complex stability, while the free energy indicates the spontaneity/non-spontaneity of derivative-DNA binding process, indicating the spontaneity of the interaction between the organoboron complexes and DNA.Furthermore, the binding constant  analysis were also conducted to determine the displacement of the intercalating agent ethidium bromide (EB) dye from CT-DNA. As example, the fluorescence emission of compound 6a was monitored by increasing the compound concentration at a fixed concentration of CT-DNA pre-treated with EB dye . High values were obtained for the quenching constant rate (kq), which were higher than the diffusion rate constant (kdiff ≈ 7.40 × 109 L mol-1 s-1 at 298K) (2-complexes and EB-DNA (via ground state association.The EB-DNA competition experiment shows an intense emission band located at λat 298K) . These od EB-DNA , which t4a-i, 5e, 6a-i, and 7e were evaluated for them in vitro antimicrobial activity against a panel of microorganisms including yeasts, filamentous fungi, bacteria, and alga by determining their MIC and minimal fungicidal/bactericidal/algacidal concentrations using broth microdilution methods according to CLSI standard protocols . These results are encouraging, since P. zopfii is an environmental agent of bovine mastitis that causes many losses resulting from the compromised quality and production of milk and, in addition, it presents high antimicrobial resistance and the optimal treatment strategy for this infection has not yet been well established. In addition, P. zopfii can cause cutaneous and serious systemic infections in humans . These results showed that changes in the basic structure as well as in the substituent slightly increased activity against P. zopfii.Considering the antimicrobial activity of the synthesized compounds, the algaecidal action against n humans . The comCandida spp. and Cryptococcus gattii) only compound 6i showed moderate activity for both, the other compounds of series 6 (6b-h) were moderately effective in inhibiting only the growth of C. gattii, as well as compounds 4a, 4b, 5e, and 7e. Compounds 4a-i and 5e have the same substituents as compounds 6a-i and 7e although the basic structure is comprised only by a β-enaminoketone for the former, whereas for compounds 6a-i and 7e a basic structure is constituted by a boron complex. Compounds 6a-j and 7e showed moderate activity against C. neoformans, and remained inactive against S. cerevisiae. Considering the difficulty in treating meningitis caused by C. gattii, which is normally resistant to one of the main antifungal drugs used in this pathology, fluconazole, increasing the mortality rate, potential treatment alternatives are extremely necessary.In relation to the evaluated pathogenic yeasts  were chosen. It is important to note that the antifungal therapy for these microorganisms is difficult and therapeutic failures are frequent , concentrations two or more times higher were required to inhibit A. niger growth. Compound 4g showed moderate activity against A. flavus (MIC = 20 µg/ml), which is the second most important agent of aspergillosis.Significant results were observed for compounds 4i against all the filamentous fungi studied when compared with 6i. The incorporation of BF2 resulted in the acquisition of antifungal activity. This shows that substituents in the boron complexes can bring significant differences in antimicrobial activities.Another interesting point is the lack of activity of 6c (MIC = 5.0 µg/ml) and 6i (MIC = 5.0 µg/ml), which were both against K. pneumoniae, and an opportunistic gram-negative rod. This is curious because, in general, the gram-positive cocci, which is represented here by S. aureus, is more sensible than gram negative rods  (61–90%), which may be used to obtain a new series of 2,2-difluoro-3-alkyl(aryl)-4-phenyl-6-(trichloromethyl)-2H-1,3,2-oxazaborinin-3-ium-2-uides  in moderate to very good yields (50–91%). Unfortunately, it was not possible to obtain the trifluoromethyl-substituted analogs.In summary, the aim of this study was to evaluate the synthetic potential of β-methoxyvinyl trichloromethyl ketones for the synthesis of trichloromethyl substituted β-enaminoketones  and the interaction of the boron complexes 6a-i and 7e against CT-DNA, which was studied by UV–Vis absorption spectroscopy.WR, IR, MR, NZ, and HB: These researchers and students were responsible for the development of the part concerning the synthesis, purification, NMR, GC-MS and X-ray diffractometric data, and TD-DFT calculations for the new compounds. HC, LD, and PL: These researches were responsible for the development of the part related to the evaluation of the minimum inhibitory concentration (MIC) of the series of compounds The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


N-acetyl glucosamine (GlcNAc) in sulfolane is described. The reaction produces two major products that are assignable to 1,6-anhydro-2-acetamido-2-deoxy-β-d-glucopyranose (AGPNAc) and 1,6-anhydro-2-acetamido-2-deoxy-β-d-glucofuranose (AGFNAc). In order to reveal a general feature of the system, the 3, 5, and 10 min reactions were performed at 140, 160, 180, 200, and 220 °C to clarify the time course changes in the conversion of GlcNAc and the yields of the two produced 1,6-anhydrosugars. Temperature is a crucial factor that significantly affects the conversion of GlcNAc. The yields of AGPNAc and AGFNAc are also drastically changed depending on the reaction conditions. The 5-min reaction at 200 °C is shown to be the optimal condition to generate the 1,6-anhydrosugars with a high efficiency in which AGPNAc and AGFNAc are produced in the yields of 21% and 44%, respectively. Consequently, the microwave-assisted heating reaction of GlcNAc in sulfolane is shown to be a simple and promising pathway to generate 1,6-anhydrosugars consisting of amino monosaccharide backbones, which have high potentials as raw materials leading to biological oligosaccharides and biomimetic polysaccharides.The microwave-assisted heating reaction of  The 1H 2O (3.0 mL). The resultant mixture was subjected to HPLC.To the starting material  in a 20 mL test tube, liquefied sulfolane (5.0 mL) was added. Further details about the microwave-assisted heating reaction have been reported elsewhere . The rea2Cl2, then 9% MeOH/CH2Cl2) to give 1,6-anhydro-2-acetamido-2-deoxy-β-d-glucopyranose (AGPNAc)  and 1,6-anhydro-2-acetamido-2-deoxy-β-d-glucofuranose (AGFNAc)  as colorless solids. AGPNAc and AGFNAc were crystallized from i-PrOH/AcOEt and MeOH/AcOEt, respectively, to give the samples for the analyses. Data for AGPNAc: mp 190–191 °C, Rf = 0.40 (CH2Cl2/MeOH 6:1), [α]D25 − 46.1° ; lit. +) 226.0686, found 226.0686; Anal. calcd for C8H13NO5: C, 47.29; H, 6.45; N, 6.89. Found C, 47.11; H, 6.41; N, 6.79. Data for AGFNAc: mp: 197–198 °C; Rf = 0.32 (CH2Cl2/MeOH 6:1); [α]D25 + 41.6° ; 1H NMR : δ 5.10 , 4.40–4.42 , 4.42–4.45 , 4.36 , 3.86 , 3.86 , 2.02 ; 13C NMR : δ 176.9 (NC=O), 105.7 (C-1), 82.4 (C-5), 78.4 (C-3), 68.6 (C-4), 66.2 (C-6), 62.9 (C-2), 24.4 (CH3CON); HRMS (ESI): m/z calcd for C8H13NO5Na ([M + Na]+), 226.0686, found 226.0685; Anal. calcd for C8H13NO5: C, 47.29; H, 6.45; N, 6.89. Found C, 47.08; H, 6.61; N, 6.91. (Microwave-assisted heating of GlcNAc (100 mg) in liquefied sulfolane (5 mL) was repeated 4 times at 220 °C for a 5-min irradiation time. The combined reaction mixtures were then directly purified twice by column chromatography on silica gel ; lit.  mp 190–1O); lit.  mp 189–1N, 6.91. .3 . The mixture was then directly purified by short column chromatography on silica gel  to give 1,6-anhydro-2-acetamido-2-deoxy-3,4-O-diacetyl-β-d-glucopyranose (AGPNAcDA) . AGPNAcDA was crystallized from AcOEt/hexane to give a sample for the analysis. Data for AGPNAcDA: mp 138.5–139.5 °C, [α]D25 − 95.5° ; lit. +), 310.0897, found 310.0897; Anal. calcd for C12H17NO7: C, 50.17; H, 5.96; N, 4.88. Found C, 50.10; H, 6.10; N, 4.87.  was added to a suspension of AGPNAc  in ethyl acetate (4 mL), a catalytic amount of DMAP, and pyridine . After stirring at room temperature for 1 h, an ethanol (0.2 mL) solution in ethyl acetate (2 mL) was added to the mixture, followed by NaHCO3); lit.  mp 137–1H); lit.  mp 139 °N, 4.87. .O-diacetyl-β-d-glucofuranose (AGFNAcDA)  as a colorless syrup. Data for AGFNAcDA: [α]D25 − 11.1° ; 1H NMR : δ 6.22 , 5.16 , 5.11 , 4.7 , 4.64 , 4.63 , 4.33 , 3.96 , 2.19 and 2.17 , 2.04 ; 13C NMR : δ 170.6 (NC=O), 170.2 and 170.1 (each OC=O), 102.9 (C-1), 77.4 (C-5), 75.9 (C-4), 66.1 (C-3), 63.2 (C-6), 58.3 (C-2), 22.9 (CH3CON), 21.1 and 20.6 (2× CH3COO); HRMS (ESI): m/z calcd for C12H17NO7Na ([M + Na]+), 310.0897, found 310.0897.  to give 1,6-anhydro-2-acetamido-2-deoxy-3,5-10.0897. .N-acetyl glucosamine (GlcNAc) in sulfolane has been demonstrated, which is shown to be a facile methodology to produce two types of 1,6-anhydro amino sugars in the forms of the pyranose ring and/or furanose ring, such as 1,6-anhydro-2-acetamido-2-deoxy-β-d-glucopyranose (AGPNAc) and 1,6-anhydro-2-acetamido-2-deoxy-β-d-glucofuranose (AGFNAc). In particular, AGFNAc has been, for the first time, synthesized and fully assigned. The yields of AGPNAc and AGFNAc are significantly dependent on the reaction temperature within the short reaction times up to 10 min. The 5 min reaction at 200 °C was shown to be one efficient condition to transform GlcNAc (91% conversion) into AGPNAc (21% yield) and AGFNAc (44% yield). This simple method with a good reproducibility integrates the use of 1,6-anhydrosugars consisting of amino monosaccharide backbones.The microwave-assisted heating reaction of