Synthetic access to syn-functionalised chiral hydroxy pyrrolidines and pyrrolidones: Evaluation of α-glucosidase inhibition activity, docking studies and pharmacokinetics prediction

An approach towards (+)-allokainic acid via diphenylprolinol-catalyzed direct cross-aldol reaction

“…As shown in Scheme 2, 2-(2-methyl-1,3-dioxolan-2-yl)acetaldehyde 15 was subjected to a cross-aldol reaction with ethyl glyoxylate (polymer form) 16 using 5 mol% of ( S )- a , a -diphenyl-2-pyrrolidinemethanol as the organocatalyst in THF/H 2 O solvent system according to our already established protocol for the synthesis of hydroxy pyrrolidones and pyrrolidines. 17 The resulting mixture was stirred for 24 h to get the cross-aldol adduct 18 . Compound 18 without any further purification was directly reacted with p -methoxybenzylamine 17 which underwent sequential imine formation, reduction and cyclization in a one pot manner to afford a highly functionalized γ -lactam 13 in 58% overall yield, 97% ee and good diastereomeric ratio of 94 : 6.…”