The synthesis of Waltherione F and 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 3, one of those alkaloids, was synthesised in 5 steps in 11% overall yield. 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

4,5-Bis(dimethylamino)quinolines: Proton Sponge versus Azine Behavior

Two first representatives, <b>5</b> and <b>6</b>, of the still unknown 4,5-bis(dimethylamino)quinoline have been synthesized and studied. While the former, being protonated either at the peri-NMe₂ groups or at the ring nitrogen, has been shown to display properties of both a proton sponge and azine, its counterpart <b>6</b> behaves exclusively as azine giving only a quinolinium salt