The Synthesis of Waltherione F and Its Analogues with Modifications at the 2- and 3-Positions as Potential Antitrypanosomal Agents.
Chagas disease also know as American Trypanosomiasis (AT) is a tropical parasitic disease endemic in South America, is caused by Trypanosoma cruzi, which is transmitted by the blood-sucking insect vectors called triatomine bugs. Quinoline alkaloids from the root extract of Waltheria indica are known to possess antitrypanosomal activity. Waltherione F, one of those alkaloids, was synthesised in 5 steps in 11 % overall yield. We report here the first X-ray crystallographic confirmation of the structure of Waltherione F 3. A key step in the sequence utilised the Conrad-Limpach synthesis for the formation of the quinolin-4(1H)-one ring system. Our synthetic strategy was designed to enable the modification of the 2- and 3-positions of the scaffold, allowing the generation of a diverse library of analogues to support our on-going medicinal chemistry program that is looking for new agents to tackle this devastating disease.
['Zdorichenko|Victor|V|', 'Paumier|Romain|R|', 'Whitmarsh-Everiss|Thomas|T|', 'Roe|Mark|M|', 'Cox|Brian|B|http://orcid.org/0000-0002-5980-9707']
D000470:Alkaloids D018360:Crystallography, X-Ray D019660:Malvaceae D008968:Molecular Conformation D018517:Plant Roots D011804:Quinolines D015363:Quinolones D014344:Trypanocidal Agents D014349:Trypanosoma cruzi
waltherione F trypanosomiasis quinoline heterocycles medicinal organic chemistry