An Efficient Synthesis of Dichotomine A via Cyclization of L-Tryptophan Derivative

Abstract

INTRODUCTION β-Carbolines represent a large group of alkaloids widely distributed in nature, occurring in plants, marine organisms and insects, most importantly, in foods and in human tissues and body fluids. They have diverse medicinal properties 1-6 such as inhibition of topoisomerase and monoamine oxidase, binding to benzodiazepine and serotonin receptors and intercalating into DNA. Dichotomines A, B, C and D, new β-carboline-type alkaloids, were first isolated from the roots of Stellaria dichotoma in 2004 7. They showed an antiallergic effect on ear passive cutaneous anaphylaxis reaction in mice and inhibitory activity on the release of β-hexosaminidase in RBL-2H3 cells. As shown in Fig. 1, the structure of dichotomines A, B, C and D include a chiral group respectively. Although many methodologies concerned the synthesis of β-carbolines 8-13 , the synthesis of dichotomines is quite limited. Dichotomine C was obtained by Omura and co-workers 14 based on the microwave assisted thermal electrocyclic reaction of a 1-azahexatriene system. Nemet and Defterdarovic 15 had synthesized dichotomine A as racemic mixture via reactions of L-tryptophan or L-tryptophan methyl ester with methyl glyoxal under acidic conditions. Zhang and co-works 16 had synthesized dichotomines A, B, C and D starting from L-tryptophan methyl ester and 2,3-Oisopropylidene-D-glyceraldehyde. From this total synthesis, dichotomine A was obtained in 13 steps and only in 24 % yield. So, we developed a new synthetic method for dichotomine A, which could reduce steps and obtain a higher yield. We chose L-tryptophan and L-lactic acid as raw material because they were inexpensive, commercially available and