A short approach for the synthesis of 3,4‐fused γ‐lactone‐γ‐lactam bicyclic systems (1) in diastereomeric mixtures from chiral D‐alanine methyl ester hydrochloride is described. The key step towards lactonisation is the reduction of the carbonyl ketone of the 5R‐configured 3,5‐dimethylpyrrolidine‐2,4‐dione diastereomers (8) via sodium borohydride in the presence of hydrochloric acid. With the presence of ethyl acetyl functionality at C3‐position, ester hydrolysis of 8 occurred concomitantly with keto reduction leading to lactonisation and eventually affording the anticipated (3S,4S,5R), (3R,4R,5R), (3R,4S,5R) and (3S,4R,5R) bicyclic moieties. The formation of the fused systems was confirmed by mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses.

The family of Simaroubaceae is known to contain quassinoids and canthin-6-ones, secondary metabolites that have been reported to possess numerous biological activities such as anticancer. A biomimetic total synthesis of canthin-6-one using Pictet-Spengler condensation according to the procedure by Czerwinski et al. (2003) was explored. The aim of this study was to determine the viability of this reaction for structural modification. In this report, influential factors of carboxyl mediated Pictet-Spengler condensation reaction would be discussed.