Nereididae as the most dominant family with ten species; however, more than half of the total are questionable species in the country. Despite the increased efforts of polychaete studies in the past decade, the taxonomic endeavour of discovering and describing species in the country could be higher. Malaysian polychaetes were mostly recorded from Peninsular Malaysia, whereas very few were from Borneo Island. Most previously recorded species were associated with intertidal and estuarine habitats and a few were found in the subtidal and freshwater environments. We stress the need for urgent research on this biologically, ecologically and culturally relevant taxonomic group as the species accumulation curve grows exponentially in this megadiverse country.An updated comprehensive checklist of polychaete species, which have been recorded from Malaysian waters, is provided, with their geographic distributions and the research history for them. A total of 57 species belonging to 30 families have been reported since the early 1870s, with The current checklist has been updated since the previous one in 2013. Many species previously listed were judged as doubtful and not taxonomically reliable. Polychaetes are predominantly marine, with some species inhabiting fresh and terrestrial groundwaters . This taMalaysia is one of the world’s megadiverse countries . DespiteThe latest previous checklist of polychaetes in Malaysia was published by Here, an updated checklist of Malaysian polychaetes is provided, re-evaluating the previous checklist and adding current information.Prionospio sp. in Previous taxonomic and ecological papers (until 2022), in which Malaysian polychaetes were identified to the species level by taxonomic specialists with or without descriptions of specific characteristics, were analysed. In the cases where records were tentatively treated at genus level in literature, only those with taxonomic remarks were here included . The bathymetric information of the polychaete was arranged by a 10 m depth interval. The distribution was shown by the following five habitat zones: estuary, intertidal, subtidal, freshwater and unknown zones . The single specimen is currently deposited at the MNHN (IA-TYPE 0326), which was collected probably in Pulau Pinang  or Singapore on any date between 17 and 26 February 1836 by Charles Gaudichaud-Beaupré in a circumnavigation carried out on board the French corvette La Bonite . The first study focused on polychaetes at the Strait of Malacca, considered as one of the busiest shipping lanes in the world, following behind the Dover Strait back in those days . The emia Bonite .There were expeditions in the IMPA  or the Malay Archipelago . One of Various national and international research studies were undertaken in the early 1960s up to recent years , originally described from Indian waters, in the eastern coast of Peninsular Malaysia, whose reproductive biology, epitokal morphology and swimming behaviour was later described in detail  from the east coast of Peninsular Malaysia.Almost a decade later, of Morib  and the of Jeram . Later on detail . In addiThe accumulative curve of the records of species in Malaysia Fig.  indicate19D78CB1-45D5-5A1A-9B8E-B692E8CD2DB6Horst, 1911ED3FDC14-C725-54AE-BD52-0749F99CEDEAType locality. North Ubian Islands, Malaysia.Distribution in Malaysia. North Ubian Islands, Malaysia.Distribution outside Malaysia. Only from type locality .0887BF81-CAC1-5157-BDE2-73E129B69BD9Grube, 18754A70F460-27D8-544F-9976-5DCBB6C915E5Type locality. North Borneo, Malaysia; Palawan, Philippines.Distribution in Malaysia. North Borneo, Malaysia .Distribution outside Malaysia. Philippines ; IndonesE45E24A6-CA0D-5C2B-A5A3-314D0D8CFBD0Sars, 1851603EA6FA-E3E0-5D74-9FA1-DB133BAD924DType locality. Komagfjord, Norway.Distribution in Malaysia. Questionable record: Kuala Terengganu River estuary, Terengganu .Distribution outside Malaysia. Italy ; EnglandE1A4FC16-BEB2-5B4E-8110-733F66F4440492675A11-9B3E-5130-A828-59F0F87B2993Type locality. Morib, Selangor, Malaysia.Distribution in Malaysia. Only from type locality .Sasekumariaselangora Rullier, 1976. The porcellanid crab Polyonyxvermicola Ng & Sasekumar, 1993 is an obligate commensal of tubes of the chaetopterid worm 78313E53-6891-5622-B871-539D2262D883Type locality. Mediterranean Sea, Italy.Distribution in Malaysia. Questionable record: Selangor River estuary .Distribution outside Malaysia. Japan .E4B1ADCF-28A3-5474-8DAC-522E1C08109B2EF98D57-8F47-5887-BB2D-A28E77ABB3E4Type locality. South coast of Devonshire, United Kingdom.Distribution in Malaysia. Questionable record: Kuala Terengganu River estuary, Terengganu .Distribution outside Malaysia. China ; Thailan1E8BC451-5006-580A-9713-9DCE6E89A6CDBF37B4ED-ACCA-5D60-BA8B-E50E65093E83Type locality. Simonstown, South Africa.Distribution in Malaysia. Questionable record: Teluk Aling, Penang .Distribution outside Malaysia. Australia ; India .6CB98700-C816-5B7A-90D6-99056A7AC2D9Nishi, 2001FF47FFD3-CACB-5D6A-A3C1-88FA1A031B16Type locality. Morib Beach, Selangor, Malaysia.Distribution in Malaysia. Only from type locality .Living in chaetopterid tubes.46C7187B-C4F1-5CDD-8BA4-71349BAED3FA967F6745-A6CE-5B46-BC0F-8A8DF5CBDD13Distribution in Malaysia. Along west of Peninsular Malaysia .Idris, Hutchings & Arshad, 2014EDE375D0-85A4-59BF-BE6D-D21359A273E0Type locality. Morib, Selangor, Malaysia.Distribution in Malaysia. Morib, Selangor and Pengkalan Balak, Malacca .Marphysacf.sanguinea by Locally known as ‘Ruat bakau’ and harvested as bait worms. Previously identified as 5C325372-7ED0-5E37-A374-FE6A060F5772DD03B828-E90E-550F-BAC5-3618421C65D7Type locality. Norway .Distribution in Malaysia. Questionable record: Selangor River estuary; Kuala Terengganu River estuary, Terengganu .Distribution outside Malaysia. Mozambique ; VietnamGrube, 1874690BD211-9213-5445-83F8-A43D08053533Type locality. Indian Ocean, Sri Lanka.Distribution in Malaysia. Teluk Aling, Penang .Distribution outside Malaysia. Andaman, Nicobar coast ; MyanmarGlyceraprashadi Fauvel, 1932.Previously recorded as CDEBD018-3529-51ED-9472-E7F59E6CD621Reibisch, 1895F540E15C-7837-5B70-96BF-EA9671E58A69Type locality. Tropical Atlantic.Distribution in Malaysia. Questionable record: Strait of Malacca .Distribution outside Malaysia. Mexico ; Eastern3B7980A0-FCB3-508D-A703-04CA84949AC2Grube, 185560AEF568-6204-55C9-A470-C0000D43FDE1Type locality. Mediterranean Sea.Distribution in Malaysia. Questionable record: Strait of Malacca .Distribution outside Malaysia. Red Sea, Gulf of Aden ; MexicanViguier, 18865C78C287-8961-5720-ABB6-BF9EF974B24AType locality. Algiers Bay, Algeria.Distribution in Malaysia. Questionable record: Strait of Malacca .Distribution outside Malaysia. Western North Pacific ; Off NorGreeff, 18794B9E296C-F964-56F4-8024-F57D50DE932EType locality. Canary Islands, Tropical Atlantic.Distribution in Malaysia. Questionable record: Strait of Malacca; Selangor River estuary .Distribution outside Malaysia. Gulf of Aden, Arabian Sea ; Vietnam2ABE0EF1-5869-5BDE-94B1-5848AEB68C3436C4AAFF-5BB9-5550-BE45-BB4E71E7F43EType locality. Port Swettenham (currently known as Port Klang), Selangor, Malaysia.Distribution in Malaysia. Kapar mangrove forest, Klang, Selangor; Kuala Lumpur .Lumbriconereismalayensis (sic) Rullier, 1969 2E41692E-C4D6-5645-B5D1-81D6D2E32C18Type locality. Rhode Island, United States.Distribution in Malaysia. Questionable record: Kuala Terengganu River estuary, Terengganu .Distribution outside Malaysia. Delaware Bay, United States .Lumbrinerisacuta Verrill, 1875.Previously recorded as A6A357A8-D6B8-5E2F-BD3B-4C6940F96423Peters, 1854DC598FCC-D4CB-54A8-AE4F-85D4C997AFE6Type locality. Mozambique, Indian Ocean.Distribution in Malaysia. Selangor River estuary .Distribution outside Malaysia. Singapore ; Africa 710E402A-AF03-50B0-B52D-AFC7C235BA0CDistribution in Malaysia. Pekan, Pahang .Glasby, Miura, Nishi & Junardi, 20074F38FD5E-2578-58D2-882A-D8697941FD51Type locality. Kalimantan, Indonesia.Distribution in Malaysia. West coast of Peninsular Malaysia and Kota Kinabalu, Sabah, Borneo .Distribution outside Malaysia. West Kalimantan, Indonesia .Known as nypa palm worm and locally known as ‘Ruat nipah’ and ‘Punpun nipah’. Used as bait for fish and shrimp .6B08562B-78B6-5B80-AE96-289C147B16BEType locality. Near Calcutta, India.Distribution in Malaysia. Jeram Beach, Selangor; Tumpat, Kelantan Delta, Kelantan; Setiu Lagoon, Terengganu; Kuala Ibai, Terengganu .Distribution outside Malaysia. India ; MyanmarCeratonereis (Composetia) burmensis Monro, 1937 89B048CF-9E5C-5D7A-AE96-49E968648D89Type locality. Aibuhit, Philippines.Distribution in Malaysia. Setiu Wetlands, Terengganu .Distribution outside Malaysia. Taiwan, Philippines, Thailand, Indonesia, Australia .8CE39C24-5687-53D6-B308-F7EE1D866714Distribution in Malaysia. Batu 4, Port Dickson, Negeri Sembilan .Locally known as ‘Ruat pasir’ and ‘Punpun pasir’.834B1251-CF27-5A29-BD89-97B4578516A6Type locality. Gulf of Naples, Italy.Distribution in Malaysia. Questionable record: Pulau Aur, Johor .Distribution outside Malaysia. Algerian Mediterranean coast ; Italy ; India ; France Wu, Sun & Yang, 1981A4278E0D-86E3-5A2F-A084-33B488275570Type locality. Aotou, Guangdong; Beihai, Beilongwei and Qisha, GuangXi, China.Distribution in Malaysia. Blue Lagoon, Port Dickson, Negeri Sembilan .Distribution outside Malaysia. China ; Hong Ko400315C0-CB6C-525B-8008-8B5CF78C41D8Type locality. Vancouver, Canada.Distribution in Malaysia. Questionable record: Kuala Terengganu River estuary, Terengganu .Distribution outside Malaysia. United States ; Japan .BFC445E9-4C67-586D-A241-C2756DECF3E0Type locality. Valparaíso, Chile.Distribution in Malaysia. Questionable record: Pulau Aur, Johor .Distribution outside Malaysia. Chile ; souther4DADA735-FC01-5781-BC7B-23E2C7ECCAEBImajima, 19673275D0EC-3607-51CE-B52C-1F51328EB73AType locality. Seto Inland Sea, Japan.Distribution in Malaysia. Questionable record: Malacca .Distribution outside Malaysia. Japan ; China ; southerLocally known as ‘Ruat beting’ in Malacca, Malaysia.E865B185-E3D7-5513-B332-37516D45BBDBGrube, 1878744F5F88-0F88-5D93-B072-390E4D0E3E9CType locality. Sungei Buloh, Singapore.Distribution in Malaysia. Along mud-flats on the west coast of Peninsular Malaysia; Jeram Beach, Selangor .Distribution outside Malaysia. Singapore ; India .Locally known as ‘Ruat sarung’.delle Chiaje, 1841890C241F-35F0-58EC-982B-2E8C1CB78887Type locality. Gulf of Naples, Italy.Distribution in Malaysia. Questionable record: Kapar mangrove forest, Klang; Teluk Aling, Penang .Distribution outside Malaysia. Red Sea, Indian Ocean ; MediterA44B0B2D-75E3-5294-B9AA-54982B2A4CBE94CD2F85-3397-5C99-839C-A4EEB3F8FED0Type locality. Casamance, Senegal.Distribution in Malaysia. Questionable record: Teluk Aling, Penang .Distribution outside Malaysia. Western Africa ; Gulf ofBB3AF16D-48F8-59B0-80F3-62679AAD1A88Type locality. Kalkudah, Sri Lanka.Distribution in Malaysia. Teluk Aling, Penang .Distribution outside Malaysia: Sri Lanka .FFC3D233-89E3-531F-BFB2-DA95E454D4B3CA066FD1-C01F-596B-823F-1E68C5296D77Type locality. Algeria, Mediterranean Sea.Distribution in Malaysia. Questionable record: Strait of Malacca .Distribution outside Malaysia. Mediterranean, warm North Atlantic, Japan .B96E3387-9C54-5ED0-90E1-87C50141E4F2Type locality. Sicily, Italy.Distribution in Malaysia. Questionable record: Strait of Malacca .Distribution outside Malaysia. Mediterranean Sea, tropical and subtropical Atlantic and Pacific Oceans, India .Treadwell, 1906AF34C67A-36D9-594C-84EB-982600FE14C2Type locality. Mediterranean Sea.Distribution in Malaysia. Questionable record: Strait of Malacca .Distribution outside Malaysia. Pacific and Atlantic Oceans ; Bangka 889C1A96-A956-5E59-9324-1835AD22FCEC84C1059E-A735-51B8-A6B1-96841E986522Type locality. El Salvador, Pacific Ocean.Distribution in Malaysia. Questionable record: Selangor River estuary .Distribution outside Malaysia. Central America ; El SalvAllen, 1904BE4B490B-B142-5083-822E-DB7EC62EC31BType locality. Plymouth, England.Distribution in Malaysia. Questionable record: Teluk Aling, Penang .Distribution outside Malaysia. English Channel, Irish Sea, Skagerrak Azores, Canary Island, Mediterranean Sea, South Africa, Gulf of Mannar, Waltair ; ArabianF75C777A-3B05-5843-8F77-CF5F10E2EE3E493B6A72-4CC3-583A-BEA1-AB2A388B49CFMichaelsen, 18921BDD7904-97FA-52BD-9C3A-78713741DAB9Type locality. Sri Lanka, Indian Ocean.Distribution in Malaysia. Strait of Malacca .Distribution outside Malaysia. New England ; Marmara7E752D2E-B719-514B-88DC-EE45CFBC7139Type locality. Strait of Malacca, Malaysia.Distribution in Malaysia. Only from type locality .Distribution outside Malaysia. Digha coast ; Indo-WeIphionecimex de Quatrefages, 1866.Originally recorded as 4B02827D-7D87-588A-BCBF-112EB0FA96C3Type locality. Port Swettenham (currently known as Port Klang), Selangor, Malaysia.Distribution in Malaysia. Kapar mangrove forest, Klang; Port Klang, Selangor .Distribution outside Malaysia. Thailand .Lepidonotuskumari Rullier, 1970.Previously recorded as 381D61B1-9AA2-571C-A053-595738BD94CCNishi, Matsuo, Capa, Tomioka, Kajihara, Kupriyanova & Polgar, 20151FF4F53B-29F0-5AD8-86C0-A12390CC82EFType locality. Jeram Beach, Selangor, Malaysia.Distribution in Malaysia. Only from type locality .9334AEC0-1DD0-591C-91D5-5EB9E07883EC30F2F4EC-195B-50FD-9C38-4F5E3EF62DDEType locality. Saint Vincent and the Grenadines, Caribbean Sea.Distribution in Malaysia. Questionable record: Teluk Aling, Penang .Distribution outside Malaysia. Colombian Caribbean .Jones, 19747A271182-50A5-57C2-8C57-F3DD8EAEE10FType locality. Ranau, Sabah, Malaysia.Distribution in Malaysia. Kinabatangan and Gunung Kinabalu, Sabah and Sarawak .Distribution outside Malaysia. Philippines .Currently, the only freshwater species in Malaysia. Paratypes collected from the Robin River at Dana Amu in Sarawak .8BA503C8-EBF0-51A6-9A4E-D6C99BD731A2Fauvel, 19289D71E128-9610-57CE-BFB7-FB1BBDF62042Type locality. Shingle Island, India.Distribution in Malaysia. Teluk Aling, Penang .Distribution outside Malaysia. Gulf of Oman ; Israel,293959E4-7CDD-567F-A49B-465F0E6DD300E0616A57-3EEC-5774-B435-D4075FA4AF73Type locality. Admirality Islands, Bismarck Archipelago, Papua-New Guinea.Distribution in Malaysia. Teluk Aling, Penang .Distribution outside Malaysia. Western Pacific Ocean, Red Sea, Persian Gulf, Gulf of Oman, Andaman Sea, Gulf of Thailand, Japan .Grube, 1857FA5B00F6-860C-5FCC-8F9F-E408920C8E69Type locality. Valparaíso, Chile.Distribution in Malaysia. Questionable record: Teluk Aling, Penang .Distribution outside Malaysia. Peru, Chile, New Zealand, India, South China Sea .F8FE65DD-D97B-5764-8397-77A90B8FCD1DE205815E-ACB0-542F-8A64-A5AE7FADDBF3Type locality. Talcahuano, Chile.Distribution in Malaysia. Questionable record: Selangor River estuary; Kuala Terengganu River estuary .Distribution outside Malaysia. Korea ; Gulf of381C2997-2270-5D67-8A83-10E3320BC8D9Distribution in Malaysia. Teluk Aling, Penang .P.malmgreni Claparède, 1869; however, the author, It showed similar features to 45003EDF-1EB3-5269-9A83-2ECEC2F3DF1011A505C7-E29A-55DD-9527-E60DA6086988Type locality. Turkey, Izmar Bay, Aegean Sea.Distribution in Malaysia. Questionable record: Selangor River estuary; Kuala Terengganu River estuary .Distribution outside Malaysia. Mediterranean Sea to the English Channel ; Korea .It was re-described by E1DDF356-1C89-5CF3-8A17-6C9C764C4AB3Rathke, 1843BA02B1BB-1F18-53FD-9CF7-00721D6EC926Type locality. NorwayDistribution in Malaysia. Questionable record: Teluk Aling, Penang .Distribution outside Malaysia. Norway ; Iberian7E147149-FBDD-518A-B0F1-2DC57CBC0329F125E8AF-D608-52A0-AC3A-7AB31F3ADE5BType locality. Galle, Sri Lanka.Distribution in Malaysia. Teluk Aling, Penang .Distribution outside Malaysia. Benin ; India .A4B26846-957E-5B5E-8A75-D6E1F81E0E5ERosa, 19081586C454-CAF4-509D-8769-6F1BE0BDC3E8Type locality. Off Oaxaca, Mexico, Pacific Ocean.Distribution in Malaysia. Questionable record: Strait of Malacca .Distribution outside Malaysia. Mexican Pacific .Rosa, 1908F4E737C3-FE15-5B06-ACDF-0813AFA7AF25Type locality. Sri Lanka, Indian Ocean.Distribution in Malaysia. Strait of Malacca .Distribution outside Malaysia. Sri Lanka ; VietnamGreeff, 188508F6C170-D3DB-5F51-BDF3-1CFBC1E4FE1EType locality. Tropical Atlantic.Distribution in Malaysia. Questionable record: Strait of Malacca .Distribution outside Malaysia. China .Rosa, 190850D0CC60-F40A-58B7-8CBE-DAF2D18EF010Type locality. Off Brazil.Distribution in Malaysia. Questionable record: Strait of Malacca .Distribution outside Malaysia. California ; Spain .81C8FC70-19E8-5938-AD22-DE900BFC2B89Busch, 18517C83A470-E2A6-52D8-8D47-2F728D68FFCBType locality. Trieste, Adriatic Sea.Distribution in Malaysia. Questionable record: Strait of Malacca .Distribution outside Malaysia. Atlantic Ocean ; SoutherA total of 57 species belonging to 47 genera in 30 families of polychaetes were recorded from Malaysian coastal waters; 53 species were recorded from Peninsular Malaysia, three species from Borneo and one species from both geographical regions. Amongst them, ten species  were originally described from Malaysia, whereas the presence of other 30 (53%) species is questionable.Caobangiaabboti, Marphysamoribidii, Neanthesglandicincta and Namalycastisrhodochorde were recorded at more than one location in Malaysia.The bathymetric information Fig.  indicateNereididae, with ten species  require a detailed revision since some may belong to cryptic or pseudocryptic species , approximately 53% .File: oo_901762.xlsxhttps://binary.pensoft.net/file/901762Raz Shauqeena Batrisyea Razmi Shah43285B26-72C1-5C00-913A-723D8B83FC0710.3897/BDJ.11.e110021.suppl2Supplementary material 2Occurrences of speciesData typeTableBrief descriptionContains the occurrences of the species with their location, depth and habitat. These data have been used to construct the bathymetry distribution map.File: oo_913194.xlsxhttps://binary.pensoft.net/file/913194Raz Shauqeena Batrisyea Razmi Shah


Purine scaffolds constitute a starting point for the synthesis of numerous chemotherapeutics used in treating cancer, viruses, parasites, as well as bacterial and fungal infections. In this work, we synthesized a group of guanosine analogues containing an additional five-membered ring and a sulfur atom at the C-9 position. The spectral, photophysical, and biological properties of the synthesized compounds were investigated. The spectroscopic studies revealed that a combination of the thiocarbonyl chromophore and the tricyclic structure of guanine analogues shifts the absorption region above 350 nm, allowing for selective excitation when present in biological systems. Unfortunately, due to the low fluorescence quantum yield, this process cannot be used to monitor the presence of these compounds in cells. The synthesized compounds were evaluated for their effect on the viability of human cervical carcinoma (HeLa) and mouse fibroblast (NIH/3T3) cells. It was found that all of them display anticancer activity. In vitro studies were preceded by in silico ADME and PASS analyses, which confirmed that the designed compounds are promising candidates for anticancer agents. The purine ring is an important structural component of many naturally occurring N-heterocycles, such as nucleic acids, nucleoside metabolites, coenzymes, and alkaloids. Over recent years, the modified purine skeleton has become one of the most common elements used in drug design and development . Due to The thiopurines, such as 6-mercaptopurine or 6-thioguanine, are examples of drugs based on the purine ring system. They are used in the treatment of cancer, especially lymphoblastic leukemia in children ,5 and arE. coli) purine-nucleoside phosphorylase (PNP) + 322.1151, found 322.1153. In the second step, General Procedure C was applied using 6-methyl-1,N2-ethenoguanosine , P2S5 , and 1,4-dioxane (20 mL). 6-methyl-9-thio-1,N2-ethenoguanosine (yield 53%) and 6-methyl-9-thio-1,N2-ethenoguanine (yield 35%) were obtained as the main products. 2-ethenoguanosine: 1H NMR  δ (ppm)6-methyl-9-thio-1,N: 1.92 , 2.45 , 3.80 , 3.91 , 4.15 , 4.37 , 4.74 , 6.03 , 8.01 , 8.36 ; 13C NMR  δ (ppm): 9.48 (-CH3), 62.82 (C-5′), 69.15 (C-3′), 73.93 (C-2′), 85.89 (C-4′), 88.62 (C-1′), 107.33 (C-7), 128.72 (C-6), 130.13 (C-10), 140.77 (C-2), 143.24 (C-11), 144.14 (C-12), 166.13 (C=S); HRMS (ESI) calculated for C13H15N5O4S [M+H]+ 338.0923, found 338.09212-ethenoguanine: 1H NMR  δ (ppm):6-methyl-9-thio-1,N 1.91 , 2.44 , 7.91 , 8.57 ; HRMS (ESI) calculated for C8H6N5S [M+Na]+ 228.0319, found 228.0314 2-ethenoguanosine (TEGuo)/9-thio-1,N2-ethenoguanine (TEGua):9-thio-1,N The title compounds were synthesized following, in the first step, General Procedure B using guanosine , sodium chloride , and chloroacetaldehyde  dissolved in 900 mL of water. 1,N2-ethenoguanosine was obtained as a main product (yield 45%); HRMS (ESI) calculated for C12H13N5O5 [M+H]+ 308.0994, found 308.0991. In the second step, General Procedure C was applied using 1,N2-ethenoguanosine , P2S5 , and 1,4-dioxane (10 mL). 9-thio-1,N2-ethenoguanosine (yield 56%) and 9-thio-1,N2-ethenoguanine (yield 32%) were obtained as the main products. 2-ethenoguanosine: 1H NMR  δ (ppm)9-thio-1,N: 1.92 , 3.80 , 3.91 , 4.15 , 4.37 , 4.74 , 6.03 , 7.53 , 8.26 , 8.36 ; 13C NMR  δ (ppm): 61.53 (C-5′), 70.69 (C-3′), 74.16 (C-2′), 85.73 (C-4′), 88.62 (C-1′), 110.57 (C-6), 117.51 (C-7), 129.98 (C-10), 141.01 (C-2), 143.57 (C-11), 144.79 (C-12), 166.42 (C=S); HRMS (ESI) calculated for C12H13N5O4S [M+H]+ 324.0766, found 324.0764 2-ethenoguanine: 1H NMR  δ (ppm)9-thio-1,N: 1.91 , 7.44 , 8.13 , 8.57 ; HRMS (ESI) calculated for C7H5N5S [M+H]+ 192.0343, found 192.0338 2-ethenoguanosine (6-Me-TEG)2′,3′,5′-tri-O-acetyl-6-methyl-9-thio-1,N: The title compound was synthesized following General Procedure D using 6-methyl-9-thio-1,N2-ethenoguanosine , anhydrous pyridine (20 mL), and acetic anhydride (2.5 mL). Yield 95%; 1H NMR  δ (ppm): 2.06 , 2.09 , 2.17 , 2.45 , 4.44–4.39 , 4.50–4.45 , 5.74 , 6.09 , 6.22 , 8.01 , 8.22 ; 13C NMR  δ (ppm): 9.48 (-CH3), 18.88 (-CH3), 19.05 (-CH3), 19.20 (-CH3), 62.82 (C-5′), 70.58 (C-4′), 72.56 (C-3′), 79.96 (C-2′), 86.85 (C-1′), 107.33 (C-7), 128.72 (C-6), 130.13 (C-10), 140.77 (C-2), 143.24 (C-11), 144.14 (C-12), 166.13 (C=S), 169.77 (5′-OC(O)-), 170.03 (3′-OC(O)-), 170.83(2′-OC(O)-); HRMS (ESI) calculated for C19H21N5O7S [M+H]+ 464.1239, found 464.1245.The spectral data for the synthesized compounds are provided in −1) for solutions with absorbance at the excitation wavelength less than 0.1. The fluorescence quantum yields were determined using 10-methylacridinium cation in water (Φ = 1.0) as a standard [UV-vis absorption spectra were recorded using a Cary 100 spectrophotometer scanning from 800 to 200 nm with 1 nm increments in 1 cm × 1 cm quartz cells. Emission spectra were taken in 1 cm × 1 cm quartz cells on a JASCO FP–8300 spectrofluorometer  [Theoretical determination of the drug-like physicochemical and pharmacokinetic properties of the synthesized compounds was assessed using the SwissADME webserver (er 2021) . The comer 2021) . The pre−5 M and 2.0 × 10−5 M) were measured spectrophotometrically, according to the Beer–Lambert law. The absorbances were recorded at λmax of the appropriate compound against a suitable phosphate buffer blank. A quantity of 1 mL of the solution of the tested compound in the phosphate buffer at pH 7.4 and 1 mL of n-octanol were placed in 2 mL Eppendorf tubes. The samples were shaken manually (2 min), vortexed (5 min), and incubated for 5 h at 25 °C or 37 °C. Then, the tubes were centrifuged . Both layers were carefully separated, and the absorbances were measured for the aqueous layers at a suitable λmax against the blank of the phosphate buffer at a suitable pH. The given logPo/w values are the mean of three independent experiments (one experiment: 3 samples for 2 concentrations of each compound).The partition coefficients of the tested compounds were determined for n-octanol/phosphate buffer pH 7.4 at 25 °C and 37 °C. The initial concentrations of the compounds . For the purpose of cytotoxicity assays, cells (from both cell lines) were seeded at a density of ca. 5000 cells/well on a 96-well microplate , in 4 replicates. 6-Me-TEGuo, 6-Me-TEGua, TEGuo, TEGua, and 6-Me-TEG were tested for their potential cytotoxicity using the following concentrations: 160 (except 6-Me-TEG), 80, 40, 20, 10, 5, and 2.5 μM. Additionally, 6-thioguanine (6TG) in concentrations of 10, 7.5, 5, 2.5, 1.25, and 0.625 μM was tested. All assays included non-treated cells and cells treated with 10% DMSO as negative and positive controls, respectively. The cells were incubated for 24 h under standard culture conditions. Cytotoxicity was measured as cell viability with the CellTiter-Glo® Luminescent Cell Viability Assay  according to the manufacturer’s protocol. The microplate luminescence was measured using an Infinite® 200 PRO plate reader . Then, the average luminescence of non-labeled cells was equated to 100%, and the remaining values were proportionally normalized. The IC50 values were calculated from the fitting curves using Origin 2022.The cytotoxicity of the synthesized compounds was tested using cell lines of cervical cancer (HeLa) and mouse fibroblasts (NIH/3T3). Both cell lines were cultured in Dulbecco′s Modified Eagle′s medium  supplemented with 10% fetal bovine serum , 1% Glutamax , and 1% Antibiotic-Antimycotic (Biowest) under standard culture conditions . The results were expressed as the mean ± standard deviation (SD) and considered significant at a p-value ≤ 0.05.The statistical analysis of the data was performed using GraphPad Prism version 9.0.0 for Windows. Data were analyzed by one-way analysis of variance (ANOVA) followed by Tukey’s test , acute myeloid leukemia (AML), and colon cancer (LoVo), will allow us to determine the potential applications of this new group of compounds.In silico prediction of ADME properties, toxicity, and drug-likeness suggests that all the compounds are promising candidates for the development of biologically active agents. In vitro analysis showed that TEGuo, 6-Me-TEGuo, and 6-Me-TEGua exhibited antitumor activity against HeLa cells with an IC


We report here, as proof of concept, a first variant (s-AlHAl) bearing p-hexadecyl-N,N-dimethylaniline (DMAC16) units, which enhances solubility in aliphatic hydrocarbons. The novel s-AlHAl was used successfully as an activator/scavenger in ethylene/1-hexene copolymerization in a high-temperature solution process.The dinuclear aluminum salt {[ Several high-performance polyolefin resins are produced with molecular catalysts in solution ,2,3. TheiBu2(PhNMe2)Al]2(μ-H)}+[B(C6F5)4]− ]+ fragment [2]+ release from methylalumoxane (MAO) [AlHAl can be viewed as a “tamed” version of the highly unstable [AliBu2]+ species [ansa-zirconocene precatalyst turned out to occur at [Al]/[Zr] and [Zr] values as low as 50 and ~10−7 M, respectively  etherate complex (abcr), DMAC16 , and 1,2-dichlorobenzene  were purchased and used as received. Ethene  was purified by flowing through a column containing activated 4 Å molecular sieves and an activated Cu catalyst (BASF R0-11G). 1-hexene  was purified by passing it through a mixed-bed column of activated Cu catalyst and 4 Å molecular sieves. Toluene , pentane , and ISOPAR-G were dried by using an MBraun SPS-5 solvent purification unit. Dichloromethane  was dried over calcium hydride, distilled and freeze–pump–thaw degassed on a high-vacuum line. Cat-Zr was synthesized according to reported procedures +[B(C6F5)4]Cl, was suspended in fresh pentane and isolated by filtration (275 mg). An aliquot of [(p-C16H33)PhN(Me)2H]Cl  was then transferred in a Schlenk flask along with Li[B(C6F5)4] etherate complex  and dissolved in dichloromethane (10 mL). The resulting turbid mixture was stirred at room temperature for 3 h, observing formation of a white precipitate over time. The volatiles were removed under vacuum and the residue was extracted with toluene, filtered, dried under vacuum, and washed with pentane to obtain [(p-C16H33)PhN(Me)2H]+[B(C6F5)4]− as a white solid .ocedures , a 2 M s1H NMR : 6.83 , 6.15 , 5.13 , 2.34 12-CH2-CH3), 1.66 , 1.43 12-CH2-CH3), 1.37–1.27 12-CH2-CH3), 1.30 12-C2H-CH3), 0.91 12-CH2-C3H) ppm. 13C NMR : 147.3 (quaternary aromatic C), 137.1 (quaternary aromatic C-N), 130.5 (aromatic m-CH), 118.1 (aromatic o-CH), 46.5 (N-CH3), 35.0 (-CH2-CH2-(CH2)12-CH2-CH3), 31.0 (-CH2-CH2-(CH2)12-CH2-CH3), 29.9–29.1 (-CH2-CH2-(CH2)12-CH2-CH3), 22.7 (-CH2-CH2-(CH2)12-CH2-CH3), 14.0 (-CH2-CH2-(CH2)12-CH2-CH3) ppm.s-Al and s-AlHAl. TIBAL  was added to a stirred suspension of [(p-C16H33)PhN(Me)2H]+[B(C6F5)4]−  and DMAC16  in toluene (2 mL) at room temperature. The mixture rapidly turns from deep to pale orange, and effervescence is observed. After stirring for 16h, the volatiles were removed under vacuum, and the residue washed with pentane to give s-Al as a pale orange ionic liquid . An aliquot of s-Al  was then dissolved in a solution of DIBAL-H (20 mmol) in ISOPAR-G  or pentane  to obtain s-AlHAl, which can be isolated in quantitative yield as a pale orange oil upon removal of volatiles under vacuum.s-Al. 1H NMR : 7.00 , 6.65 , 2.50 12-CH2-CH3), 1.99 , 1.55 12-CH2-CH3), 1.51 2), 1.40–1.29 12-CH2-CH3), 1.30 12-C2H-CH3), 0.95 2), 0.92 12-CH2-C3H), 0.05 2) ppm. 13C NMR : 144.1 (quaternary aromatic C), 142.4 (quaternary aromatic C-N), 129.7 (aromatic m-CH), 120.4 (aromatic o-CH), 46.7 (N-CH3), 34.8 (-CH2-CH2-(CH2)12-CH2-CH3), 31.2 (-CH2-CH2-(CH2)12-CH2-CH3), 29.9–29.1 (-CH2-CH2-(CH2)12-CH2-CH3), 27.8 (Al-CH2-CH(CH3)2), 25.8 (Al-CH2-CH(CH3)2), 22.8 (-CH2-CH2-(CH2)12-CH2-CH3), 20.5 (Al-CH2-CH(CH3)2), 14.0 (-CH2-CH2-(CH2)12-CH2-CH3) ppm.s-AlHAl. 1H NMR : 7.04 , 6.82 , 2.91 , 2.48 12-CH2-CH3), 2.43 , 1.53 12-CH2-CH3), 1.62 2), 1.41–1.23 12-CH2-CH3), 1.31 12-C2H-CH3), 0.94 12-CH2-C3H), 0.92 2), 0.87 2), 0.10 2) ppm. 13C NMR : 143.8 (quaternary aromatic C), 142.1 (quaternary aromatic C-N), 130.0 (aromatic m-CH), 119.9 (aromatic o-CH), 46.8 (N-CH3), 34.8 (-CH2-CH2-(CH2)12-CH2-CH3), 31.2 (-CH2-CH2-(CH2)12-CH2-CH3), 29.9–29.1 (-CH2-CH2-(CH2)12-CH2-CH3), 27.7 (Al-CH2-CH(CH3)2), 25.5 (Al-CH2-CH(CH3)2), 22.7 (-CH2-CH2-(CH2)12-CH2-CH3), 21.9 (Al-CH2-CH(CH3)2), 14.0 (-CH2-CH2-(CH2)12-CH2-CH3) ppm.Tp = 100 °C; p(C2H4) = 12 bar ; 1-hexene initial concentration in reaction solution of 3.7 v/v% was used , fully contained in a triple MBraun glovebox operating under nitrogen. The cells, each with a liquid working volume of 6.0 mL, featured an 800 rpm magnetically coupled stirring, and individual online reading/control of temperature, pressure, monomer uptake, and monomer uptake rate. Experiments were carried out according to established experimental protocols ,50,51, uused see . Convers2 flow), to remove any contaminants and leftovers from previous experiments. After cooling to glovebox temperature, the module stir tops are taken off, and the 48 cells are fitted with disposable 10-mL glass inserts  and polyether ether ketone (PEEK) stir paddles. The stir tops are then set back in place, and N2 in the reactors is replaced with ethene (ambient pressure).Prior to the execution of a polymerization library, the PPR modules undergo “bake-and-purge” cycles overnight , containing TIBAL as a scavenger where appropriate, and 1-hexene. The system is then thermostated at the reaction temperature and brought to 12 bar of pressure with ethene. At this point, the catalyst injection sequence is started; aliquots of (a) an ISOPAR-G “chaser”, (b) a toluene solution of catalyst, (c) a toluene solution of the proper activator, and (d) a ISOPAR-G “buffer” are uploaded into the needle and subsequently injected into the cell of destination in reverse order, thus starting the reaction. This is left to proceed under stirring (800 rpm) at constant temperature and pressure with feed of ethene on demand until the desired monomer consumption has been reached , where all volatiles are removed, and the polymers are thoroughly dried overnight. The dry polymers were robotically weighed while still in the reaction vials, subtracting the prerecorded tare. Reaction yields are double-checked against online monomer conversion measurements. Polymer aliquots are then sent to the characterizations.13C NMR spectroscopy. GPC curves were recorded with a Freeslate Rapid GPC setup, equipped with a set of two mixed-bed Agilent PLgel 10-μm columns and a Polymer Char IR4 detector. Calibration was performed with the universal method by using 10 monodisperse polystyrene samples (Mn between 1.3 and 3700 kDa).All polymers were characterized by means of high-temperature gel permeation chromatography (GPC) and 13C NMR spectra were recorded by using a Bruker Avance III 400 spectrometer equipped with a high-temperature cryoprobe for 5-mm OD tubes, on 45-mg mL−1 polymer solutions in tetrachloroethane-d2 . Acquisition conditions were: 45° pulse; acquisition time, 2.7 s; relaxation delay, 5.0 s; 2 K transients. Broadband proton decoupling was achieved with a modified WALTZ16 sequence .Quantitative s-AlHAl was synthesized by adapting the previously optimized procedure for AlHAl and its mononuclear precursor Al +[B(C6F5)4]− having long N-alkyl substituents  +[B(C6F5)4]− (RIBS), was used as a benchmark /[Zr] ratios. These results represent a first demonstration that the AlHAl cocatalyst frame can be structurally amplified and tailored for specific applications; further variants are being prepared and screened in our laboratories, as will be reported in due course.In this paper, we introduced a novel molecular activator of the


Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic activity. In this article, we present an efficient method for obtaining novel 2-oxindole derivatives via microwave-assisted (MW) decarboxylative condensation of substituted isatins with malonic and cyanoacetic acids. Various 3-hydroxy-2-oxindoles were synthesized using MW activation for 5–10 min with high yields (up to 98%). The influence of novel compounds applied in instillations on IOP was studied in vivo on normotensive rabbits. The lead compound was found to reduce the IOP by 5.6 Torr (ΔIOP for the widely used antiglaucomatousic drug timolol 3.5 Torr and for melatonin 2.7 Torr). Glaucoma is the most frequent cause of irreversible blindness since it leads to the irreversible loss of retinal ganglion cells and optic nerve fibers ,2,3. UnfAs a rule, the primary treatment of open-angle glaucoma is carried out through pharmacotherapy. The main risk factor for glaucoma is ocular hypertension, which is an increase in intraocular pressure (IOP). The increase in IOP leads to damage to the optic nerve head, ischemia, and the loss of ganglion cells in the retina. Therefore, most antiglaucomic drugs are aimed at lowering IOP. Currently, there are six classes of ophthalmic drugs used in the treatment of glaucoma: prostaglandin analogues , carboniA limited number of IOP-influencing molecular targets leads to the fact that patients develop tolerance and drugs no longer work. For example, some beta-blockers have a 30% chance of tachyphylaxis or drug tolerance development in 1 month ,15,16. FRecently, considerable attention has been paid to melatonin and dopamine receptors as promising targets in the search for antiglaucoma drugs ,18, whicIn general, the synthesis of several 3-cyanomethyl- and 3-carboxymethyl-3-hydroxyoxindoles is carried out by the condensation of isatins with cyanoacetic or malonic acids with simultaneous decarboxylation . However1b,c,e,h) were obtained using the Sandmeyer reaction from the corresponding anilines. Nitroisatins  were obtained by the nitration of isatin (1g) or 5-methoxyisatin (1c) according to the described procedures [The starting isatins  with cyanoacetic or malonic acids in the presence of an organic base under conventional reflux for 3 h leads to the formation of 3-hydroxy-3-cyanomethyloxindoles (2a–h) and 3-hydroxy-3-carboxymethyloxindoles (3a–h), respectively  with cyanoacetic and malonic acids proceeds with simultaneous decarboxylation by two alternative mechanisms, A and B. In the case of condensation with cyanoacetic acid, mechanism A is assumed acetic acid (3g), but 2-(3 -hydroxy-2-oxoindolin-3-yl)propanedioic acid (X) (Mechanism xylation . This reacid (X) .2 and 3, the diastereotopically different CH2 protons are well resolved in 1H NMR spectra  compared to melatonin or timolol 5 h after instillation are statistically significant .1H and 13C NMR spectra were recorded at 298 K on a Bruker Avance 400 spectrometer with an operating frequency of 400 and 100 MHz, respectively, and calibrated using residual CHCl3 (δH = 7.26 ppm) and CDCl3 (δC = 77.16 ppm) or DMSO-d5 (δH = 2.50 ppm) and DMSO-d6 (δC = 39.52 ppm) as internal references. NMR data are presented as follows: chemical shift (δ ppm), multiplicity , coupling constant (J) in Hertz (Hz), integration. IR spectra were recorded on the Thermo Nicolet IR-200 in KBr or ZnSe. High-resolution mass spectra (HRMS) were measured on a Thermo Scientific LTQ Orbitrap instrument using nanoelectrospray ionization (nano-ESI). HPLC was measured using acetonitrile as the eluent on a Shimadzu Prominence LCMS-2020.The 1,4-dioxane was distilled over sodium. The triethylamine and piperidine were dried over NaOH. Reactions were monitored by thin-layer chromatography (TLC) carried out on Merck TLC silica gel plates (60 F254), using UV light for visualization and basic aqueous potassium permanganate or iodine fumes as developing agents. Flash column chromatography purification was performed using silica gel 60 (particle size 0.040–0.060 mm). The melting points were measured in open capillaries and are presented without correction. The reactions under microwave irradiation were carried out in a Monowave 300 microwave reactor , as well as in a Bosch HMT72M420 domestic microwave oven with a volume of 17 L. Reactions under thermal activation conditions were carried out on laboratory hot plates, as well as in a ChemiStation chemical reactor (EYELA).All obtained compounds were sufficiently pure  in a mixture of dioxane and triethylamine . Three types of reaction vessels were used: A chemical test tube with a screw cap (10 mL volume) in method A, a heavy-walled pressure vessel with a PTFE snap cap (30 mL volume) in method B, and a single-necked round-bottom flask (50 mL volume) in method C. The reaction mixture was vigorously stirred until the complete dissolution of the acid.Cyanoacetic acid (1 eq.) or malonic acid (2.2 eq.) were added to a solution of isatin derivative Method A:The reaction vessel was placed in a domestic microwave oven under radiation of 360W for 2 min. After that, the reaction vessel was slowly adjusted to ~50 °C, then quickly cooled to room temperature using a cool water bath and again placed in a domestic microwave oven for 2 min at the same power. The cycle of cooling and irradiation was repeated twice more.Method B:The mixture in the reaction vessel was stirred with reflux for 3 h.Method C:The reaction vessel was placed in a microwave reactor. In the device settings, the temperature was set to 120 °C, the stirring intensity to 600 rpm, and the time to 3 min. Every 3 min, the reaction flask was cooled to room temperature. The cycle of cooling and irradiation was repeated twice more.The mixture in the reaction vessel was stirred with reflux for 3 h.Purification :2SO4 (anhydrous), and the organic solvent was removed in vacuo. The following compounds had been obtained according to these procedures:The reaction mixture was evaporated to dry in vacuo. The residue was washed with 3 mL of 10% HCl. The product was dissolved in 5 mL EtOAc, dried over Na2a) [acetonitrile (2a) .1a), 0.1 g (1.18 mmol) of cyanoacetic acid, 2 mL of pure dioxane, and 0.1 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 211 mg (method A) and 269 mg (method B) of solid product were obtained. Yield 77% (method A) and 98% (method B). NMR spectra are identical.Briefly, 227 mg (1.18 mmol) of 5-nitro-1H-indole-2,3-dione (1H (DMSO-d6): 3.14 ; 3.21 ; 7.12 ; 8.26 ; 8.33 .NMR 2b).acetonitrile (1b), 0.1 g (1.18 mmol) of cyanoacetic acid, 2 mL of pure dioxane, and 0.1 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 184 mg (method A) and 209 mg (method B) of solid product were obtained. Yield 67% (method A) and 76% (method B). NMR spectra are identical.Briefly, 227 mg (1.18 mmol) of 7-nitro-1H-indole-2,3-dione (1H (DMSO-d6): 3.14 ; 7.23–7.31 ; 7.85 ; 8.09 ; 11.34 .NMR 2c) [acetonitrile (2c) .1c), 0.1 g (1.18 mmol) of cyanoacetic acid, 2 mL of pure dioxane and 0.1 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 154 mg (method A) and 180 mg (method B) of thick oil product were obtained. Yield 60% (method A) and 70% (method B). NMR spectra are identical.Briefly, 209 mg (1.18 mmol) of 5-methoxy-1H-indole-2,3-dione (1H (DMSO-d6): 2.94 ; 3.04 ; 3.71 ; 6.77 ; 6.85 ; 7.08 ; 10.37 .NMR 13C (DMSO-d6): 24.48, 55.54, 72.21, 110.47, 111.14, 114.48, 116.94, 132.37, 134.62, 155.16, 182.85.NMR 2d).acetonitrile (1d), 0.1 g (1.18 mmol) of cyanoacetic acid, 2 mL of pure dioxane and 0.1 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 133 mg (method A) and 170 mg (method B) of thick oil product were obtained. Yield 43% (method A) and 55% (method B). NMR spectra are identical.Briefly, 262 mg (1.18 mmol) of 5-methoxy-4-nitro-1H-indole-2,3-dione (1H (DMSO-d6): 3.09 ; 3.84 ; 7.03 ; 7.07 ; 7.28 ; 10.89 .NMR 2e) [acetonitrile (2e) 1e), 0.1 g (1.18 mmol) of cyanoacetic acid, 2 mL of pure dioxane, and 0.1 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 248 mg (method A) and 226 mg (method B) of solid product were obtained. Yield 80% (method A) and 73% (method B). NMR spectra are identical. M.p. = 137 °C  of 5-methoxy-7-nitro-1H-indole-2,3-dione (5–130 °C ).1H (DMSO-d6): 3.10–3.20 ; 3.83 ; 7.50 ; 7.54 ; 11.22 .NMR 13C (DMSO-d6): 25.68, 56.23, 70.77, 106.18, 116.72, 120.09, 130.94, 132.01, 134.85, 154.48, 176.86.NMR 2f) [acetonitrile (2f) .1f), 0.1 g (1.18 mmol) of cyanoacetic acid, 2 mL of pure dioxane, and 0.1 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 266 mg (method A) and 253 mg (method B) of solid product were obtained. Yield 81% (method A) and 77% (method B). NMR spectra are identical.Briefly, 280 mg (1.18 mmol) of 5,7-dinitro-1H-indole-2,3-dione (1H (DMSO-d6): 3.23–3.34 ; 8.62 ; 8.83 ; 12.03 .NMR 2g) [acetonitrile (2g) .1g), 0.1 g (1.18 mmol) of cyanoacetic acid, 2 mL of pure dioxane, and 0.1 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 146 mg (method A) and 135 mg (method B) of thick oil product were obtained. Yield 66% (method A) and 61% (method B). NMR spectra are identical.Briefly, 173 mg (1.18 mmol) of 1H-indole-2,3-dione (1H (DMSO-d6): 2.94 ; 3.04 ; 6.87 ; 6.99–7.06 ; 7.24–7.31 ; 7.43–7.50 ; 10.56 .NMR 2h) [acetonitrile (2h) .1h), 0.1 g (1.18 mmol) of cyanoacetic acid, 2 mL of pure dioxane, and 0.1 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 227 mg (method A) and 249 mg (method B) of solid product were obtained. Yield 72% (method A) and 79% (method B). NMR spectra are identical.Briefly, 267 mg (1.18 mmol) of 5-bromo-1H-indole-2,3-dione (1H (DMSO-d6): 3.02 ; 3.10 ; 6.83 ; 7.47 ; 7.59 ; 10.71 .NMR 13C (DMSO-d6): 25.74, 72.04, 112.15, 113.61, 116.94, 127.09, 132.13, 132.70, 140.98, 176.20.NMR 2i)acetonitrile (1i), 0.1 g (1.18 mmol) of cyanoacetic acid, 2 mL of pure dioxane, and 0.1 mL of triethylamine were involved in the reaction under the conditions of method A. After extraction, 218 mg of solid product was obtained. Yield 60%.Briefly, 351 mg (1.18 mmol) of 1-benzyl-5-methoxy-1H-indole-2,3-dione (1H (DMSO-d6): 3.07 ; 3.19 ; 3.71 ; 4.86 ; 6.78 ; 6.85 ; 7.18 ; 7.23–7.36 .NMR 13C (DMSO-d6): 26.17, 42.79, 55.58, 72.20, 110.19, 111.32, 114.23, 116.97, 127.18, 128.56, 135.21, 135.88, 144.58, 155.70, 174.92.NMR 3a) [acetic acid (3a) .1a), 0.2 g (1.92 mmol) of malonic acid, 3 mL of pure dioxane, and 0.5 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 191 mg (method A) and 193 mg (method B) of solid product were obtained. Yield 86% (method A) and 87% (method B).Briefly, 168 mg (0.88 mmol) of 5-nitro-1H-indole-2,3-dione (1a), 0.4 g (3.85 mmol) of malonic acid, 15 mL of pure dioxane, and 1.0 mL of triethylamine were involved in the reaction under the conditions of method C. After extraction, 441 mg of solid product was obtained. Yield 92%.Briefly, 336 mg (1.75 mmol) of 5-nitro-1H-indole-2,3-dione .1H (DMSO-d6): 2.96 ; 3.21 ; 6.40 ; 6.99 ; 8.18 ; 8.26 ; 11.00 .NMR 3b) [acetic acid (3b) .1b), 0.2 g (1.92 mmol) of malonic acid, 3 mL of pure dioxane, and 0.5 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 215 mg (method A) and 206 mg (method B) of solid product were obtained. Yield 97% (method A) and 93% (method B). NMR spectra are identical. M.p. = 241 °C  of 7-nitro-1H-indole-2,3-dione (2–243 °C ).1H (DMSO-d6): 3.02 ; 3.12 ; 7.15 ; 7.76 ; 8.00 ; 11.07 .NMR 3c).acetic acid (1c), 0.2 g (1.92 mmol) of malonic acid, 3 mL of pure dioxane, and 0.5 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 127 mg (method A) and 104 mg (method B) of solid product were obtained. Yield 61% (method A) and 50% (method B). NMR spectra are identical.Briefly, 155 mg (0.88 mmol) of 5-methoxy-1H-indole-2,3-dione (1H (DMSO-d6): 2.86 ; 2.92 ; 3.68 ; 6.68 ; 6.75 ; 6.96 ; 10.05 .NMR 13C (DMSO-d6): 41.54, 55.49, 73.03, 109.78, 111.20, 113.54, 132.56, 135.95, 154.72, 169.09, 178.06.NMR 11H11NO5, M + H), 260.0529 , 276.0269 , calculated for C11H11NO5 + H: 238.0710; C11H11NO5 + Na: 260.0529; C11H11NO5 + K: 276.0269.HRMS-ESI, m/z: 238.0710 (C3d) [acetic acid (3d) 1d), 0.2 g (1.92 mmol) of malonic acid, 3 mL of pure dioxane, and 0.5 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 176 mg (method A) and 181 mg (method B) of solid product were obtained. Yield 71% (method A) and 73% (method B). NMR spectra are identical. M.p. = 242 °C  of 5-methoxy-4-nitro-1H-indole-2,3-dione (0–245 °C ).1H (DMSO-d6): 2.82 ; 2.98 ; 3.79 ; 6.49 ; 6.94 ; 7.15 ; 10.53 .NMR 3e).acetic acid (1e), 0.2 g (1.92 mmol) of malonic acid, 3 mL of pure dioxane, and 0.5 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 196 mg (method A) and 208 mg (method B) of solid product were obtained. Yield 79% (method A) and 84% (method B). NMR spectra are identical.Briefly, 194 mg (0.88 mmol) of 5-methoxy-7-nitro-1H-indole-2,3-dione (1H (DMSO-d6): 2.98 ; 3.17 ; 3.81 ; 7.41 ; 7.50 ; 10.94 .NMR 13C (DMSO-d6): 42.29, 56.49, 71.54, 105.34, 113.43, 120.51, 130.66, 134.05, 154.56, 168.95, 170.75.NMR 11H10N2O7, M + H), 305.0380 , calculated for C11H10N2O7 + H: 283.0570; C11H10N2O7 + Na: 305.0380.HRMS-ESI, m/z: 283.0570 (C3f) [acetic acid (3f) .1f), 0.2 g (1.92 mmol) of malonic acid, 3 mL of pure dioxane, and 0.5 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 204 mg (method A) and 186 mg (method B) of solid product were obtained. Yield 78% (method A) and 71% (method B). NMR spectra are identical. M.p. = 239 °C  of 5,7-dinitro-1H-indole-2,3-dione (5–240 °C ).1H (DMSO-d6): 3.06 ; 3.46 ; 6.70 ; 8.65 ; 8.78 ; 11.79 .NMR 3g) [acetic acid (3g) .1g), 0.2 g (1.92 mmol) of malonic acid, 3 mL of pure dioxane, and 0.5 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 138 mg (method A) and 127 mg (method B) of solid product were obtained. Yield 76% (method A) and 70% (method B).Briefly, 129 mg (0.88 mmol) of 1H-indole-2,3-dione (1g), 411 mg (3.95 mmol) of malonic acid, 15 mL of pure dioxane, and 1.0 mL of triethylamine were involved in the reaction under the conditions of method C. After extraction, 286 mg of solid product was obtained. Yield 77%.Briefly, 264 mg (1.80 mmol) of 1H-indole-2,3-dione : 2.51 ; 2.61 ; 6.75 ; 6.86–6.92 ; 7.11–7.17 ; 7.27 ; 10.17 .NMR 13C (DMSO-d6): 45.28, 73.23, 109.40, 121.27, 123.76, 128.77, 132.52, 142.21, 172.35, 178.46.NMR 3h).acetic acid (1h), 0.2 g (1.92 mmol) of malonic acid, 3 mL of pure dioxane, and 0.5 mL of triethylamine were involved in the reaction under the conditions of methods A and B. After extraction, 194 mg (method A) and 202 mg (method B) of solid product were obtained. Yield 77% (method A) and 80% (method B). NMR spectra are identical.Briefly, 198 mg (0.88 mmol) of 5-bromo-1H-indole-2,3-dione (1H (DMSO-d6): 2.89 ; 3.02 ; 6.74 ; 7.36 ; 7.51 ; 10.37 .NMR 13C (DMSO-d6): 41.38, 72.61, 111.46, 113.01, 126.94, 131.75, 133.87, 142.14, 170.31, 177.67.NMR 10H9BrNO4, M + H), 307.9529 , calculated for C10H9BrNO4 + H: 285.9709; C10H9BrNO4 + Na: 307.9529.HRMS-ESI, m/z: 285.9709 (C3i).acetic acid (1i), 0.2 g (1.92 mmol) of malonic acid, 3 mL of pure dioxane, and 0.5 mL of triethylamine were involved in the reaction under the conditions of method A. After extraction. 161 mg of solid product was obtained. Yield 56%.Briefly, 237 mg (0.88 mmol) of 1-benzyl-5-methoxy-1H-indole-2,3-dione (1H (DMSO-d6): 3.01 ; 3.07 ; 3.67 ; 4.74 ; 4.89 ; 6.59 ; 6.73 ; 7.05 ; 7.20–7.32 ; 7.38 .NMR 13C (DMSO-d6): 41.63, 42.81, 55.54, 66.40, 72.74, 109.40, 111.21, 113.25, 127.18, 128.45, 131.97, 136.40, 136.57, 155.35, 170.39, 176.40.NMR 1g), 0.3 g (2.88 mmol) of malonic acid, 3 mL of pure dioxane, and 0.5 mL of triethylamine were involved in the reaction. A chemical test tube with a screw cap containing a reaction mixture was placed in a Bosch HMT72M420 domestic microwave oven (17 L volume) under radiation of 360W for 2 min. After that, the reaction vessel was cooled to room temperature. The reaction mixture was poured hot into a single-necked round-bottom flask, and the organic solvent was removed in vacuo. The resulting compound was washed with small portions of 10% HCl. The product was dissolved in 5 mL EtOAc, dried over Na2SO4 (anhydrous), and the organic solvent was removed in vacuo. One hundred and sixty-six milligrams of solid product was obtained. Yield 75%.A chemical test tube with a screw cap containing a reaction mixture was placed in a Bosch HMT72M420 domestic microwave oven (17 L volume) under radiation of 360W for 2 min. After that, the reaction vessel was cooled to room temperature. Briefly, 129 mg (0.88 mmol) of 1H-indole-2,3-dione (1H (DMSO-d6): 3.55 ; 6.02 ; 6.76 ; 6.88–6.94 ; 7.13–7.21 ; 7.29 ; 10.21 .NMR 13C (DMSO-d6): 41.97, 72.64, 109.50, 121.36, 123.96, 127.04, 129.20, 142.81, 168.51, 168.54, 170.33.NMR w/v); in the case of melatonin, this corresponded to a concentration of 4.3 μM. All substances were dissolved in a 0.05 M phosphate buffer solution, pH 7.4, containing 5% dimethyl sulfoxide (DMSO) v/v. All compounds were initially dissolved in DMSO and then diluted to the required concentration with phosphate buffer solution. The solutions were instilled into both eyes at a fixed volume of 50 μL. IOP was measured before instillation and then followed for 6 h at a 1 h interval using an automatic tonometer for veterinary Tonovet . Evaluation of the hypotensive effect of each compound was carried out in a group of 5 animals (10 eyes). Results were corrected for normal daily IOP fluctuations by simultaneous IOP measurement in 3 intact animals (6 eyes) instilled with a phosphate buffer solution containing 5% DMSO. Animals were taken for the next experiment after at least 7 days. Since the rate of IOP decrease varied in different animals during the study, we took into account not only the average decrease in the group at a particular time point but also the maximal IOP decrease in each eye.The ability of oxindoles to reduce IOP was assessed on normotensive male Chinchilla rabbits weighing about 2 kg. All investigated substances were used topically as 0.1% solutions (The microwave-assisted (MW) decarboxylative condensation of isatins with malonic and cyanoacetic acids is reported to give the new 3-hydroxy-2-oxindole derivatives with high yields (up to 98%). The obtained compounds were found to reduce the intraocular pressure (IOP) in normotensive rabbits nearly as effectively as melatonin and timolol (reference drugs) or even more effectively: the lead compound was found to reduce the IOP by 5.6 Torr (ΔIOP for the timolol 3.50 Torr and for melatonin 2.7 Torr). A time-dependent study revealed the prolonged effects (more than 5 h) of the synthesized compounds. This hypotensive effect without any signs of local ocular toxicity in combination with high water solubility represents a great potential for low-cost oxindole derivatives as potent antiglaucomatousic agents. The results of this pilot study suggest the prospects for further preclinical studies of the efficacy and safety of the identified leading compounds as potential antiglaucomatous drugs.


The palladium-catalyzed Sonogashira coupling of α, β-unsaturated acid derivatives offers a diversity-oriented synthetic strategy for cross-conjugated enynones. However, the susceptibility of the unsaturated C-C bonds adjacent to the carbonyl group toward Pd catalysts makes the direct conversion of α, β-unsaturated derivatives as acyl electrophiles to cross-conjugated ketones rare. This work presents a highly selective C-O activation approach to prepare cross-conjugated enynones using α, β-unsaturated triazine esters as acyl electrophiles. Under base and phosphine ligand-free conditions, NHC-Pd(II)-Allyl precatalyst alone catalyzed the cross-coupling of α, β-unsaturated triazine esters with terminal alkynes efficiently, yielding 31 cross-conjugated enynones with diverse functional groups. This method demonstrates the potential of triazine-mediated C-O activation for preparing highly functionalized ketones. Petrosia solida 2, and [PdCl]2 (Entries 9–11), substantially enhanced the activity of Pd, resulting in yields of 62–58%, respectively. NHC ligands further improved the allylic Pd(II) precatalysts Pd-1 and Pd-2, which yielded 75% and 78%, respectively (Entry 13). Remarkably, Pd-3, containing a less bulky NHC ligand, catalyzed the coupling reaction with 95% yields (Entry 14). The Pd-loading of Pd-3 as a precatalyst could be reduced to 1 mol% (Entry 16) without significantly impacting the reaction outcome. During optimization, low-yielding reactions generally showed the degradation of triazine ester into the corresponding anhydrous and no evidence of C(acyl)-O cleavage or decarbonylation pathways was observed.It is worth noting that allylic Pd(II) precatalysts, such as [Pd(cinnamyl)Cl]2a. Our findings revealed that several substitution patterns and types of cinnamic triazine esters 1a–1k provided satisfactory yields. For instance, both electron-rich and electron-poor cinnamic triazine esters, including those with para- , meta- (1h), and sterically hindered ortho- (1i) substitution patterns, were effective in producing the desired enynone products. Additionally, the coupling reaction using 3,4,5-methoxyphenyl (1j), catecholyl (1k), and furanyl (1l) cinnamic triazine testers gave 96%, 78%, and 95% yields, respectively.Under mild optimal conditions, we evaluated the potential of triazine esters as acyl electrophiles in Pd-catalyzed Sonogashira coupling reactions. Without adding a base and phosphine ligand, Pd(II) efficiently catalyzed the coupling reactions at 50 °C in MeCN. As shown in 1l–1r, which are significant in synthetic chemistry. It is important to note that acrylic triazine esters with methyl or n-propyl at both α- and β- positions can be coupled with phenylacetylene and converted to the corresponding unsaturated enynones (3ma–3oa) with high yields of 87–91%.We have expanded the protocol to include acrylic triazine esters δ-dienynones  with high yields of 94% and 88%, respectively. These extended conjugated systems would be difficult to be constructed using conventional nucleophilic addition methodologies, highlighting the practicality of these α, β-unsaturated carboxylic acid esters as acyl electrophiles.Sorbic triazine esters, which are challenging substrates, can be selectively activated at C(acyl)-O in the presence of the diene close to carbonyl groups to produce two α, β, γ, 1a) to produce the desired cross-conjugated enynones in high yields (2b–2f) and electron-withdrawing groups (2j–2k) provided satisfactory yields ranging from 60% to 95%. Sterically bulky ortho-chlorine in 2k was also fully compatible with Pd-catalyzed cross-couplings of cinnamic triazine (1a), producing the corresponding enynones with 93% yields. Enynones bearing biphenyl  were isolated in 86% yields. Aliphatic alkynes (2m) also acted as good nucleophiles coupled with the triazine ester. On the other hand, alkynes with sterically hindered groups, such as i- butyl (3an), produced the corresponding enynones 3am with a 42% yield. These results highlight the advantages of using triazine ester as acyl electrophiles for synthesizing cross-conjugated enynones with broad applicability.Various functionalized alkynes reacted efficiently with cinnamic triazine ester  employed glass 0.25 mm silica-gel plates. Flash chromatography columns were packed with 200–300 mesh silica-gel in petroleum (the boiling point was between 60–90 °C). Gradient flash chromatography was conducted eluting with a continuous gradient from petroleum to the indicated solvent, and they were listed as volume/volume ratios. 1H NMR and 13C NMR were recorded on a Bruker-400 MHz Spectrometer , using Acetonitrile-d3 as the solvent at room temperature. The chemical shifts (δ) were expressed in ppm, and the coupling constants (J) were expressed in Hz. High-resolution mass spectra (HRMS) were recorded on a Bruker MAXIS spectrometer.All reactions were performed using a 27.5 × 72.5 mm screw-caped vial under air without N1sa–1sr 1.0 mmol), NMM (1.2 mmol) and 10 mL of toluene. The reaction mixture was stirred at room temperature to completely dissolve. Then, 2-Chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) (1.2 mmol) was dissolved in 10 mL toluene into the reaction mixture dropwise. After the reaction, the resulting mixture was diluted with 20.0 mL of ethyl acetate and filtrated. The residue was washed with 1N citric acid solution, H2O, and 1N sodium bicarbonate, respectively. The organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure. Purification of the crude product by flash chromatography on silica gel using the mixed solvent system of petroleum ether (PE) and ethyl acetate (EA) afforded the desired products (1a–1r).Under an air atmosphere, a round-bottom flask of 150 mL equipped with a magnetic stir bar was charged successively with α-β unsaturated carboxylic acid , alkyne , Pd-3 (3.0 mol%). Then, MeCN (2.0 mL) was added. The reaction mixture was stirred at 50 °C. The conversion was monitored by TLC analysis, and unless otherwise noted, the triazine esters were fully converted within 12 h. The reaction mixture was diluted with 20.0 mL of ethyl acetate, filtrated, and concentrated under reduced pressure. Purification of the crude product by flash chromatography on silica gel using the mixed-solvent system of petroleum ether (PE) and ethyl acetate (EA) afforded the desired products.E)-1,5-diphenylpent-1-en-4-yn-3-one (3aa) + calcd. for C18H15O: 247.1117; Found: 247.1114.(E)-5-phenyl-1-(o-tolyl)pent-1-en-4-yn-3-one (3ia), the general method using Triazine Ester 1i and Phenylacetylene 2a gave the title compound 3ia in 85% yield; 1H NMR : δ/ppm = 8.03 , 7.74–7.64 , 7.50–7.40 , 7.36 , 7.28 , 6.92 , 2.57. 13C NMR : δ/ppm = 177.99, 148.51, 142.20, 134.21, 133.53, 131.31, 131.05, 130.03, 129.17, 128.88, 128.61, 126.18, 119.78, 90.04, 89.74. IR(KBr): ν(C≡C): 2212 cm−1; ν(C=O): 1626 cm−1. m/z:HRMS(ESI)  [M+H]+ calcd. for C18H15O: 247.1117; Found: 247.1112.(E)-5-phenyl-1-pent-1-en-4-yn-3-one (3ja), the general method using Triazine Ester 1j and Phenylacetylene 2a gave the title compound 3ja in 96% yield; 1H NMR : δ/ppm = 7.92 , 7.75–7.71 , 7.58–7.45 , 7.01, 6.89 , 3.86, 3.77. 13C NMR : δ/ppm = 177.82, 153.67, 148.82, 140.80, 132.99, 130.94, 129.76, 128.95, 127.92, 119.97, 106.43, 90.49, 86.11, 60.07, 55.94. IR(KBr): ν(C≡C): 2210 cm−1; ν(C=O): 1626 cm−1. m/z:HRMS(ESI)  [M+H]+ calcd. for C20H19O4: 323.1277; Found: 323.1270.(E)-1--5-phenylpent-1-en-4-yn-3-one (3la) + calcd. for C15H11O2: 223.0753; Found: 223.0747.(ne (3la) , the genE)-1-(furan-2-yl)-5-phenylpent-1-en-4-yn-3-one (3ka), the general method using Triazine Ester 1l and Phenylacetylene 2a gave the title compound 3la in 95% yield; 1H NMR : δ/ppm = 7.75 , 7.70–7.65 , 7.55–7.41 , 6.95 , 6.71–6.56 . 13C NMR : δ/ppm = 177.22, 150.64, 146.68, 146.62, 134.30, 132.99, 130.96, 128.95, 125.55, 119.91, 118.03, 113.30, 90.43, 85.94. IR(KBr): ν(C≡C): 2210 cm−1; ν(C=O): 1624 cm−1. m/z:HRMS(ESI)  [M+H]+ calcd. for C18H13O3: 277.0859; Found: 277.0855.(E)-2-methyl-1,5-diphenylpent-1-en-4-yn-3-one (3ma) + calcd. for C14H13O: 197.0961; Found: 197.0967.-1,7-diphenylhepta-4,6-dien-1-yn-3-one (3ra) + calcd. for C19H17O: 261.1274; Found: 261.1277.(E)-5-(4-butylphenyl)-1-phenylpent-1-en-4-yn-3-one (3ae), the general method using Triazine Ester 1a and 1-Butyl-4-eth-1-ynylbenzene 2e gave the title compound 3ae in 90% yield; 1H NMR : δ/ppm = 7.91 , 7.63–7.54 , 7.46–7.41 , 7.23 , 6.87 , 2.65 , 1.61 , 1.37 , 0.94 . 13C NMR : δ/ppm = 178.45, 148.20, 146.41, 134.21, 133.12, 131.21, 129.18, 128.93, 128.78, 128.72, 117.33, 92.42, 86.55, 35.87, 33.35, 22.40, 14.02. IR(KBr): ν(C≡C): 2194 cm−1; ν(C=O): 1627 cm−1. m/z:HRMS(ESI)  [M+H]+ calcd. for C21H21O: 289.1587; Found: 289.1585.(E)-1-phenyl-5-(m-tolyl)pent-1-en-4-yn-3-one (3af) + calcd. for C17H11OCl: 267.0571; Found: 267.0568.(E)-5--1-phenylpent-1-en-4-yn-3-one  [1a and 4-ethynyl-1,1′-biphenyl 2l gave the title compound 3al in 86% yield; 1H NMR : δ/ppm = 7.94 , 7.74 , 7.68–7.60 , 7.51–7.37 , 6.90 . 13C NMR : δ/ppm = 178.33, 148.41, 143.54, 139.89, 134.18, 133.58, 131.30, 129.21, 129.10, 128.83, 128.66, 128.29, 127.43, 127.24, 119.00, 91.76, 87.42.(E)-1-phenylnon-1-en-4-yn-3-one (3am) [1a and hex-1-yne 2m gave the title compound 3am in 80% yield; 1H NMR : δ/ppm = 7.87 , 7.73–7.60 , 7.45 , 6.79 , 2.50 , 1.63 , 1.49 , 0.96 . 13C NMR : δ/ppm = 174.23, 170.70, 162.38, 149.11, 133.75, 131.40, 129.17, 128.68, 115.88, 56.01.(ne (3am) , the genE)-6,6-dimethyl-1-phenylhept-1-en-4-yn-3-one (3an) [1a and 3,3-dimethylbut-1-yne 2n gave the title compound 3an in 42% yield; 1H NMR : δ/ppm = 7.84 , 7.70–7.65 , 7.46 , 6.79 , 1.36 . 13C NMR : δ/ppm = 178.36, 148.16, 134.22, 131.15, 129.13, 128.79, 128.69, 102.04, 77.23, 29.38, 27.69.(ne (3an) , the genThis report presents a diversity-oriented synthesis of cross-conjugated enynones through Pd-catalyzed Sonogashira coupling using triazine esters as acyl electrophiles. The study demonstrates that many triazine esters can produce cross-conjugated enynones with high-to-excellent yields under base- and phosphine-ligand-free conditions. The proposed mechanism for the reaction provides a better understanding of the reaction pathway and highlights the significance of triazine-stabilized intermediates in the Pd-catalyzed Sonogashira coupling reaction.Overall, this method can potentially expand the possibilities of triazine-mediated C-O activation in various fields. Further research is needed to investigate the full potential of this Pd-catalyzed transformation of triazine ester electrophiles, with possible future studies focusing on more challenging substrates and the development of new earth-abundant metal–catalyst systems.


Here we present a step-for-step replica of the Fischer carbene synthesis at a borylene carbonyl involving nucleophilic attack at the carbonyl carbon followed by electrophilic quenching at the resultant acylate oxygen atom. These reactions provide borylene acylates and alkoxy-/silyloxy-substituted alkylideneboranes, main-group analogues of the archetypal transition metal acylate and Fischer carbene families, respectively. When either the incoming electrophile or the boron center has a modest steric profile, the electrophile instead attacks at the boron atom, leading to carbene-stabilized acylboranes – boron analogues of the well-known transition metal acyl complexes. These results constitute faithful main-group replicas of a number of historical organometallic processes and pave the way to further advances in the field of main-group metallomimetics.The Fischer carbene synthesis, involving the conversion of a transition metal (TM)-bound CO ligand to a carbene ligand of the form [=C(OR’)R] , is one of the seminal reactions in the history of organometallic chemistry. Carbonyl complexes of  Replicating the seminal reactions of transition metals with p-block species is often very challenging. Here, the authors present a step-for-step main-group replica of the historical Fischer carbene synthesis, providing bora-Fischer carbene species. O. Fischer and A. Maasböl marked the first synthesis of a TM carbene complex1. Although the 1973 Nobel Prize in Chemistry to E. O. Fischer and G. Wilkinson was officially awarded for their independent work on sandwich complexes2, the fact that Fischer dedicated the entirety of his Nobel Lecture to transition-metal (TM) carbene and carbyne chemistry is a striking testament to the importance of metal-carbon multiple bonding. Thereafter followed decades of major advances in the field, for instance the development of the Fischer / Schrock carbene duality concept4, the Dötz reaction5, and olefin metathesis6, to name just a few. The implications of metal-carbon multiple bonding have since suffused further afield into organic chemistry, catalysis, nanoscience7 and beyond, and no teaching course on organometallic chemistry is complete without a thorough treatment of the topic.The 1964 synthesis of  24, which have shown the propensity to undergo photodecarbonylation and ligand exchange, both of which are well-established processes of TM carbonyl complexes.Despite the achievements in the chemistry of these “main-group metallomimetics”, the replication of organometallic reactions by p-block species is mostly limited to the field of small-molecule activation, and many archetypal organometallic processes still have no main-group counterparts. This is likely due to both: (a) the generally difficult synthesis and high reactivity of low-valent p-block species, and (b) limitations of the main-group metallomimetic concept itself. In other words, despite their similarities, main-group elements still have more limited oxidation state and orbital flexibility than TMs. One of the most promising families of boron metallomimetics has been the borylene mono- and dicarbonyls, of the form , L = carbene donor) might allow us to demonstrate a main-group analogue of the Fischer carbene synthesis protocol Fig. . A furth2 is the nucleophilic attack at the carbon atom of a metal-bound CO ligand, forming an anionic complex with an acylate ligand ([LnM(C(O)R)]–)  attacks at the carbon atom of [Fe(CO)5], forming the anionic acylate complex [(OC)5Fe–C(O)OH]–25. Our attempts to recreate this reaction centered on two borylene carbonyls stabilized by a cyclic (amino)carbene −3,3,5,5-tetramethylpyrrolidin-2-ylidene), namely [(CAAC)BDur(CO)]  and [(CAAC)BH(CO)]  study that provided poor data suitable for establishment of its connectivity. However, complex 2b was fully characterized by NMR spectroscopy , high-resolution mass spectrometry (HRMS) and SCXRD. Their solid-state structures indicated that complexes 2a,b were indeed the desired borylene acylate species resulting from the nucleophilic attack at the positively charged boron atom of complexes 1a,b , 1.496(9) Å; B–Cacyl 1.520(7), 1.532(8) Å; 2b: B–CCAAC 1.507(6), 1.508(6) Å; B–Cacyl 1.502(5), 1.494(5) Å). Resonances in the 11B NMR spectra of 2a,b were found at relatively high field , suggesting relatively high electron density at the boron atom. However, these are still significantly downfield of the resonances of their respective precursor borylene carbonyls , which are electron-rich, low-valent boron species. To our knowledge, only one other such borylene acylate species is known in the literature, a potassium-bound dimer reported by our group, which is generated by an unusual reduction / aryl migration process from a borylene carbonyl23. This compound has an analogous structure to 2a,b, with a delocalized OCBCN unit, B–CCAAC and B–Cacyl distances of 1.503(2) and 1.518(2) Å, and an 11B NMR resonance at 15.0 ppm.The first step of the historical Fischer carbene synthesis]–) Fig. . This stnM(C(O)R)]–, whereby the electrophile (E+) adds at the acylate oxygen atom, furnishing the Fischer carbene species [LnM = C(OE)R]2. Alternatively, attack of the electrophile at the metal center may take place, providing an acyl complex  the metal center is relatively electron poor , (b) the electrophile is sterically bulky and may struggle to approach the crowded metal site, and/or (c) the electrophile is relatively “hard” and thus a good match for an acylate oxygen nucleophile.The second step of the Fischer carbene synthesis is the electrophilic quenching of the anionic acylate complex of the form Cl) provided acylborane adduct 4a as an orange solid (36% yield), while treatment of 2b with ethyl bromide provided the analogous 4b as its pale yellow complex with lithium bromide, [LiBr(4b)2] (82% yield) 2]: –12.7 ppm, 2JBH = 84.6 Hz) thanks to coupling with their boron-bound hydrides. While acylboranes (RC(O)BR'2) and acylborates ([RC(O)BR'3]–) are well known and synthetically useful species30, to our knowledge, structurally authenticated singly base-stabilized acylboranes (RC(O)BR'2L; R = organyl group) such as 4a,b are unknown.Protonation of in-situ-generated acylate complex d) Figs. b, 2c. At2a,b with different electrophiles invites analysis in light of the determinants for electrophilic attack at either the metal or acylate oxygen of TM acylate complexes, as outlined in Fig. 27. Given that both variants occur with both borylene ([(CAAC)BR]) scaffolds, the electron density of the borylene unit itself is likely not a determinant of the reaction pathway for these compounds. This is borne out by the very similar calculated atomic dipole-moment-corrected Hirshfeld (ADCH) charges of the boron and acylate oxygen atoms of 2b . In comparison, the negative charge of the tungsten acylate complex used in the original Fischer carbene synthesis ([(OC)5M(C(O)Ph)]–) is much more concentrated at the acylate O atom than the W atom . The softness/hardness of the electrophile can also be ruled out as a factor given that there is no clear pattern of matching soft or hard electrophiles and nucleophiles in the reactions shown in Fig. 2a but the boron atom of 2b, etc.). Therefore, the electrophilic quenching reactions in Fig. 3 or 4) was the sole product in the reaction mixture at full consumption of the precursor, and the alternative isomer was not detected.The divergent reactions of the borylene acylates In conclusion, we present herein a step-for-step main-group analogue of the Fischer carbene synthesis, resulting in carbene-stabilized alkoxy-/silyloxy-substituted alkylideneboranes, which can be considered boron analogues of conventional, transition-metal Fischer carbene complexes. Alternatively, by varying the electrophilic reagent in the synthesis, boron analogues of archetypal TM acyl complexes can be prepared. These reactions extend the use of p-block species as mimics of transition metals beyond small-molecule activation by replicating multi-step syntheses that are of historical and pedagogical importance in traditional, transition-metal-based organometallic chemistry. This work also opens up diverse opportunities in developing further metallomimetic chemistry using low-valent boron species, in particular replicating well-known reactions of TM Fischer carbenes, e.g., the Dötz reaction, olefin metathesis, or the synthesis of main-group analogues of Fischer carbynes. Work in our laboratories is underway with these goals in mind.δ) are provided in ppm and internally referenced to the carbon nuclei (13C{1H}) or residual protons (1H) of the solvent. Heteronuclei NMR spectra are referenced to external standards (11B: BF32). Solid-state IR spectra were recorded on a Bruker FT-IR spectrometer ALPHA II inside a glovebox. UV-vis spectra were measured on a METTLER TOLEDO UV-vis-Excellence UV5 spectrophotometer inside a glovebox. Microanalyses  were performed on an Elementar vario MICRO cube elemental analyzer. High-resolution mass spectrometry data were obtained from a Thermo Scientific Exactive Plus spectrometer in LIFDI or ASAP mode. Syntheses of known compounds following published procedures can be found in the All manipulations were performed either under an atmosphere of dry argon or in vacuo using standard Schlenk line or glovebox techniques. Deuterated solvents were dried over molecular sieves and degassed by three freeze-pump-thaw cycles prior to use. All other solvents were distilled and degassed from appropriate drying agents. Solvents were stored under argon over activated 4 Å molecular sieves. NMR spectra were acquired on a Bruker Avance 400 or 500 NMR spectrometer. Chemical shifts (1a)  was dissolved in 20 mL of benzene and phenyllithium  was added. The reaction mixture was stirred at room temperature for 3 h and methyltrifluoromethanesulfonate  was added. After 2 h of stirring at room temperature all volatiles were removed in vacuo. The solid residue was extracted with hexane and recrystallized at –30 °C, yielding [(CAAC)B(Dur)=C(Ph)(OMe)] (3a) as a red solid in 53% yield . 1H NMR : δ = 7.08 , 6.83–6.89 , 6.78 , 6.75–6.72 , 3.24 2), 2.47 , 2.42 , 2.17 , 1.67–1.59 2), 1.33 2), 1.25 2), 1.02 2) ppm. 13C NMR  (BCqO could not be detected): δ = 194.6 (Ccarbene), 146.4 (i-Dip-Cq), 144.1 (Ph-Cq), 138.8 (o-Dip-Cq), 138.3 (m-Dur-Cq), 131.8 (o-Dur-Cq), 129.4 (Dur-CH), 129.1 (m-Ph-CH), 128.1 (Dip-CH), 126.1 (o-Ph-CH), 125.2 (p-Ph-CH), 124.0 (Dip-CH), 72.8 (NC(CH3)2), 57.1 (OCH3), 55.3 (CH2), 51.6 (CC(CH3)2), 30.3 (CC(CH3)2), 29.8 (CH(CH3)2), 29.3 (NC(CH3)2), 26.5 (CH(CH3)2), 24.5 (CH(CH3)2), 23.0 (o-Dur-CH3), 21.0 (m-Dur-CH3) ppm. 11B NMR : δ = 19.0 (s) ppm. LIFDI-HRMS calculated for [C36H52BNO] = [M]+ 549.4136; found: 549.4141.[(CAAC)BDur(CO)] (1a)  was dissolved in 0.5 mL of benzene and phenyllithium  was added. The reaction mixture was left at room temperature for 3 h and triethylammonium chloride  was added. After 2 h at room temperature all volatiles were removed in vacuo. The solid residue was washed with hexane (3 ×1 mL) and recrystallized at –30 °C from THF, yielding [(CAAC)B(Dur)(H)C(=O)(Ph)] (4a) as an orange solid in 36% yield . 1H NMR : δ = 7.37 , 7.32 , 7.20 , 7.11–7.07 , 7.02 , 6.97 , 6.66 , 4.06 , 3.10 2), 2.63 2), 2.43 (s (br), 6H, o-Dur-CH3), 2.08 (s (br), 6H, m-Dur-CH3), 2.07 , 1.99 , 1.78 2), 1.64 2), 1.43 2), 1.37 2), 1.28 2), 1.19 2), 1.18 2), 1.03 2) ppm. 13C NMR  (BCqO could not be detected): δ = 146.7 (o-Dip-Cq), 145.1 (i-Dip-Cq), 139.9 (m-Dur-Cq), 138.6 (o-Dur-Cq) 136.5 (i-Ph-Cq), 129.3 (Dur-CH), 129.2 (p-Dip-CH), 129.1 (p-Ph-CH), 127.1 (m-Ph-CH), 127.1 (m-Dip-CH), 125.7 (o-Ph-CH), 125.2 (o-Ph-CH), 77.9 (NC(CH3)2), 54.8 (CC(CH3)2), 54.7 (CH2), 30.8 (CC(CH3)2), 30.3 (NC(CH3)2), 30.2 (CH(CH3)2), 29.2 (CH(CH3)2), 29.0 (NC(CH3)2), 28.4 (CH(CH3)2), 27.5 (CH(CH3)2), 26.4 (CC(CH3)2), 25.4 (CH(CH3)2), 25.1 (CH(CH3)2), 22.5 (o-Dur-CH3), 21.3 (m-Dur-CH3) ppm. 11B NMR : δ = –14.8  ppm. LIFDI-HRMS calculated for [C36H52BNO] = [M]+ 549.4136; found: 549.4141.[(CAAC)BDur(CO)] (1b)  and mesityllithium etherate  were suspended in diethyl ether (0.7 mL). After 1 h at room temperature the reaction mixture was filtered and crystallized at –30 °C, yielding [(CAAC)B(H)=C(Mes)(OLi(OEt2))] (2b) as a red solid in 96% yield . 1H NMR : δ = 6.98 , 6.94 , 6.44 , 3.38 , 3.22 2), 2.63 , 2.16 , 2.05 , 1.95 , 1.83 2), 1.18 2), 1.15 2), 1.12 2), 1.12  ppm. 13C NMR  (BCqO could not be detected): δ = 182.3 (CCarbene), 155.4 (i-Mes-Cq), 150.0 (i-Dip-Cq), 139.4 (o-Dip-Cq), 132.9 (o-Mes-Cq), 131.6 (p-Mes-Cq), 127.5 (Mes-CH), 126.6 (p-Dip-CH), 123.8 (m-Dip-CH), 66.3 (Et2O-CH2), 66.3 (NC(CH3)2), 58.8 (CH2), 45.9 (CC(CH3)2), 31.0 (CC(CH3)2), 30.3 (NC(CH3)2), 29.1 (CH(CH3)2), 27.2 (CH(CH3)2), 24.2 (CH(CH3)2), 21.0 (p-Mes-CH3), 20.2 (o-Mes-CH3), 15.7 (Et2O-CH3) ppm. 7Li NMR : δ = 0.2 (s) ppm. 11B NMR : δ = 10.8 (s) ppm. LIFDI-HRMS calculated for [C30H44BNO] = [M-Et2O-Li]+ 445.3510; found: 445.3508.[(CAAC)BH(CO)] (1b)  and mesityllithium etherate  were suspended in diethyl ether (0.7 mL). The reaction mixture was left at room temperature for 20 min and chlorotrimethylsilane  was added. After 1 h at room temperature all volatiles were removed in vacuo. The solid residue was extracted with hexane and recrystallized, yielding [(CAAC)B(H)=C(Mes)(OSiMe3)] (3b) as a orange solid in 82% yield . 1H NMR : δ = 7.22 , 7.16 (br d (coincides with solvent), 1H, m-Dip-CH), 7.14 , 6.90 , 3.50 , 2.88 2), 2.60 , 2.20 , 1.52 , 1.50 2), 1.21 2), 1.19 2), 0.95 2), 0.22 3) ppm. 13C NMR : δ = 207.7 (Ccarbene), 181.5 (BCqO), 146.6 (i-Dip-Cq), 145.1 (i-Mes-Cq), 136.7 (o-Mes-Cq), 135.9 (o-Dip-Cq), 135.7 (p-Mes-Cq), 128.7 (p-Dip-CH), 128.5 (Mes-CH), 124.7 (m-Dip-CH), 70.9 (NC(CH3)2), 55.4 (CH2), 48.5 (CC(CH3)2), 29.8 (CC(CH3)2), 29.3 (CH(CH3)2), 28.9 (NC(CH3)2), 26.3 (CH(CH3)2), 23.9 (CH(CH3)2), 21.3 (p-Mes-CH3), 21.1 (o-Mes-CH3), 1.9 (Si(CH3)3) ppm. 11B NMR : δ = 15.3 (s) ppm. 29Si NMR : δ = 10.0 (s) ppm. LIFDI-HRMS calculated for [C33H52BNOSi] = [M]+ 517.3906; found: 517.3904.[(CAAC)BH(CO)] (1b)  and mesityllithium etherate  were suspended in diethyl ether (0.7 mL). The reaction mixture was left at room temperature for 20 min and ethyl bromide  was added. After 2 d at 60 °C all volatiles were removed in vacuo. The solid residue was extracted with hexane and recrystallized. After washing with hexane (2 ×1 mL) [((CAAC)B(H)(Et)C(=O)(Mes))2LiBr] ([LiBr(4b)2]) was obtained as a pale yellow solid in 82% yield . 1H NMR : δ = 7.37 , 7.29 , 7.28 , 6.54 , 3.23 2), 2.66 2), 2.19 , 2.12 , 2.08 , 2.05 , 2.00 , 1.66 2), 1.53 2), 1.43 2), 1.34 2), 1.30 2), 1.29 2), 1.23 2), 1.04 2), 0.72–0.62 , 0.50–0.39 , 0.44  ppm. 13C NMR  : δ = 238.0 (Ccarbene), 149.7 (i-Mes-Cq), 147.0 (o-Dip-Cq), 145.8 (o-Dip-Cq), 135.2 (p-Mes-Cq), 134.7 (i-Dip-Cq), 133.0 (o-Mes-Cq), 129.6 (p-Dip-CH), 128.8 (Mes-CH), 125.9 (m-Dip-CH), 125.2 (m-Dip-CH), 79.0 (NC(CH3)2), 54.3 (CC(CH3)2), 52.6 (CH2), 30.7 (NC(CH3)2), 30.1 (CC(CH3)2), 29.9 (CC(CH3)2), 29.7 (CH(CH3)2), 29.5 (CH(CH3)2), 28.9 (CH(CH3)2), 28.4 (NC(CH3)2), 25.7 (CH(CH3)2), 25.3 (CH(CH3)2), 24.4 (CH(CH3)2), 21.1 (o-Mes-CH3), 20.8 (p-Mes-CH3), 14.3 (BCH2CH3), 12.0 (BCH2CH3) ppm. 7Li NMR : δ = 0.7 (s) ppm. 11B NMR : δ = –12.7  ppm. LIFDI-HRMS calculated for [C32H48BNO] = [M]+ 473.3823; found: 473.3823.[(CAAC)BHCO] (3a), [(CAAC)B(H)(Dur)C(=O)(Ph)] (4a), [(CAAC)B(H)=C(Mes)(OLi(OEt2))] (2b)) a Bruker X8-APEX II diffractometer with a CCD area detector ([(CAAC)B(Dur)=C(Ph)(OLi)] (2a)), both equipped with multi-layer mirror monochromated Moκα radiation, or a Rigaku OD XtaLAB Synergy-R diffractometer with a HPA area detector, equipped with multi-layer mirror monochromated Cuκα radiation ([(CAAC)B(H)=C(Mes)(OSiMe3)] (3b) and [((CAAC)B(H)(Et)C(=O)(Mes))2LiBr] (4b)). The structures were solved using the intrinsic phasing method31, refined with the ShelXL program32 and expanded using Fourier techniques. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms were included in structure factor calculations. All hydrogen atoms were assigned to idealized positions, except the boron-bound hydrogens, which were detected in the difference Fourier map and freely refined, except when stated otherwise in the refinement details.The crystal data were collected either on a Bruker D8 Quest diffractometer with a CMOS area detector ([(CAAC)B(Dur)=C(Ph)(OMe)] (2b and Li[(OC)5W(C(O)Ph)] using the B3LYP36 functional with the D337 dispersion correction combined with the def2-SVP38 basis set. All optimized structures were verified as minimum through vibrational frequency calculations, showing no imaginary frequencies. The electronic situation of the compounds was investigated using ADCH39 charges. To support the obtained results for compound 2b, CHelpG40 charges were also calculated and are found to be in good agreement. For Li[(OC)5W(C(O)Ph)], only ADCH was applied. All geometry optimizations and frequency calculations were performed with the Gaussian 16, Revision C.01, program41. The ADCH and CHelpG charges as well as the Mayer bond orders were obtained using Multiwfn 3.8 program42.Geometry optimizations were performed in the gas phase for Supplementary Information