11-Azaartemisinin cocrystals with preserved lactam:acid heterosynthons

摘要

11-Azaartemisinin (11-Aza) is a potent anti-malarial drug more readily able to form cocrystals than its parent compound. 13 new 1:1 and 2:1 cocrystal phases from 25 mono- and bi-functional acids are reported here in excellent yield and purity by liquid assisted grinding. X-ray structures of several of these cocrystals reveal R22(8) heterosynthons with short OH-O?C H-bonds 2.60 angstrom between the 11-Aza lactam and the coformer acid groups. The new phases can show enhanced aqueous solubility of 11-Aza of 3x after 12 h. Notably diastereospecific cocrystal formation can occur, with the dl-mandelic acid system yielding solely the 11-Azaart:d-mandelic acid 1:1 product.