SYNTHESES OF 1,3-DISUBSTITUTED N-OXY-BETA-CARBOLINES BY THE PICTET-SPENGLER REACTIONS OF N-OXY-TRYPTOPHAN AND N-OXY-TRYPTAMINE DERIVATIVES

A general and simple approach for the synthesis of N-hydroxy and N-alkoxytryptophan and tryptamine derivatives is presented. Key-intermediates are nitro compounds which are easily accessible from gramine (16) and RCH2N2. Reduction with Al-amalgam gave in high yields the corresponding hydroxylamines. The N-alkoxy derivatives are accesible by a regioselective O-alkylation of oxime 12 followed by a reduction with borane-trimethylamine complex. The influence of the substituents R1-R3 on the reactivity and the relative stereochemistry in the Pictet-Spengler condensation with aldehydes (R4CHO) has been studied. The increased electrophilic character of the C=N double bond in the intermediate 38 due to the oxygen substituent on the nitrogen increases the reactivity and alters the stereoselectivity. © 1990.