Microwave accelerated Pictet-Spengler reactions of tryptophan with ketones directed toward the preparation of 1,1-disubstituted indole alkaloids

Using the Pictet-Spengler reactions of tryptophan with aldehydes under acidic conditions at ambient temperature, diastereoisomers of 1,3-disubstituted-1,2,3,4-tetrahydro-beta-carbolines could readily be furnished in short time (0.5-4 h) with good to excellent yields (50-98%). Though intrinsically slow in reaction rates, ketone reactions can be accelerated (from days to minutes) using microwaves in open vessels with high isolated yields (67-99%), making those carbolines feasible reaction intermediates for the synthesis of both natural and unnatural indole alkaloids. Preparation of two indole alkaloids, tetrahydro-beta-carbolinediketopiperazines and tetrahydro-beta-carbolinehydantoins, were briefly discussed. (C) 2004 Elsevier Ltd. All rights reserved.