Structural and Synthetic Studies in Some B-Carboline Bases

Abstract

In the context of studies in correlation of structure and activity of B-carboline bases a large number of new derivatives have been synthesized and characterized through physical and spectral data. The work carried out in the direction referred to above has been mainly concerned with: 1. Structure and activity relationship study I Peganum harmala alkaloids harmine, harmidine and tetrahydroharmine. 2. Comparative study of cyano derivatives of B-carbolines, steroidal and some simpler bases. 3. Structure and activity correlationship study in the sandwicine series of rauwolfia alkakoid. 4. Conversion of harmala alkaloids into other types of alkaloidal bases of potential therapeutic importance. 5. Nitration studies in yohimbine. As a result of extensive researches carried out with Peganum harmala alkaloids harmine,harmadine/harmaline, their common reduction product tetrahydroharmine and their demethylated products harmol and hamidol, a number of new derivatives have been obtained in high yields as noted in “result and discussion”. It was noted during the course of thes studies that Von Braun BrCN reaction undertaken with harmidine gave bromo products instead of the expected yano derivative, whereas nitration of some tetrahydroharmine derivatives involved substitution at C-2 of indole with ring opening. Extension of Von braun BrCN reaction on tetrahydroharmine, aminotetrahydroharmine, sandwicine and isosandwicine has resulted in the synthesis of a number of new derivatives of potential therapeutic importance. Coparative study of cyano derivatives of B-carbolines, steroidal and some simpler base has also been made, eith with a view to determine the scope and limitations of the applicability of these reactions. Attempts have also been made to convert harmala alkaloids into other types of useful alkaloidal bases. Partial syntheses of 11-methoxyrutaecarpine and 11-methoxynauclefine have been achieved through harmidine/harmiline. Nauclefine which is a minor indole alkaloid having b-carboline moiety in its structure has anti-leukemic properties. In the view of increasing pharmacological properties of the nitro derivatives of Rauwolfia alkaloids, it was considered of interest to extend these studies to yohimbine, a yohembehe alkaloid, also found in many Rauwolfia species. As a result of the time consuming studies, two isomeric mononitro yohimbine and their various new derivatives have been obtained, as described in detail in the following pages. The structures of all these derivatives have been assigned through spectral and chemical studies. Pharmacological studies in various derivatives are being pursued with particular reference to their psychotomimetic and anti-leukemic action, one of these derivatives, namely sulfonamide of tetrahydroharmine has been found to have analgesic property without any undesireable side effects. It is hoped that the present work and its extension may eventually lead to the utilization of the alkaloids of these abundantly available indigenous medical plants in the development of important therapeutic agents.