Enantioselective Synthesis of Hydantoin and Diketopiperazine-Fused Tetrahydroisoquinolines via Pictet-Spengler Reaction

Abstract

An enantioselective synthesis of iso-, isothio-, and isoselenohydantoin and diketopiperazine-fused tetrahydroisoquinolines from L-Dopa was reported. The route consists of an Pictet-Spengler reaction of (S)-2-amino-3-(3,4-dimethoxyphenyl)propanoates with various aldehydes to afford diastereomeric tetrahydroisoquinolines. Next step, the tetrahydroisoquinolines were further reacted with iso-, isothio-, or isoselenocyanates to construct hydantoin. Similarly, the diketopiperazine moiety was constructed by subjecting tetrahydroisoquinolines to a condensation reaction with chloroacetyl chloride followed by nucleophilic addition with various primary amines.