β‐Carbolines derived from β‐methyltryptophan and a stereoselective synthesis of (2RS,3SR)‐β‐methyltryptophan methyl ester

Abstract

AbstractThe methyl ester of isomer A of β‐methyltryptophan (2SR,3RS; 2A) was stereoselectively prepared by an efficient modified method through the reaction of a‐methyl‐N‐(1‐Methylethyl)‐1H‐indole‐3‐methanamine (3) with methyl nitroacetate to give the desired nitro compound as a mixture of two racemates 5A, and 5B. During the recrystallization process epimerization occurred and only racemate 5A crystallized out. Catalytic hydrogenation of 5A in the presence of acid stereoselectively yielded the desired amino acid ester 2A. Pictet‐Spengler condensation of 2A with aldehydes under aprotic conditions followed by dehydrogenation gave excellent yields of β‐carbolines 7a‐i, (R = methyl, ethyl, acetyl, phenyl, pyridine‐2‐yl, furan‐2‐yl, quinoline‐2‐yl, styryl, phenethyl). Also β‐carbolines 7a,b,i were synthesized by the Pictet‐Spengler condensation of (3‐meth‐yltryptophan under acidic aqueous conditions followed by esterification and dehydrogenation.