I= SYNTHETIC STUDIES IN THE FIELD OF HETEROCYCLIC CHEMISTRY
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Title of Thesis
SYNTHETIC STUDIES IN THE FIELD OF HETEROCYCLIC CHEMISTRY

Author(s)
Mumtaz Sultana
Institute/University/Department Details
University of Karachi ./H.E.J Research Institute of Chemistry
Session
1982
Subject
Chemistry
Number of Pages
185
Keywords (Extracted from title, table of contents and abstract of thesis)
heterocyclic chemistry, n-methyl secondine, tautomerism-nucleophilic reaction, b-carbolines, alkylation reactions, ketimine systems, b-aminoester

Abstract
The potant pharmacological properties of vincamine and eburnamonine as cereveral vasodilators have prompted intensive efforts culminating in several syntheses. The first chapter of this dissertation describes a formal total synthesis of (+)-vincamine and (+)-eburnamonine. The salient feature of this synthesis is a new high yield construction of the tetracylic amine (161). This tetracyclic amine is a potential intermediate for the synthesis of Hanteria alkaloids and has been utilized by wenkert, 16 Szantay 17 and Buzas 18 for the synthesis of vincamine and eburnamonine. The intial phase of the scheme has made use of stork’s reaction 43 to generate an appropriate non-tryptophan template, and the latter phase of the scheme consists of the critical condensation of tryptamine moiety with the resulting aliphatic unit and subsequent reduction of the condensed molecule to the desired intermediate which could be transformed to vincamine and eburnamonine by already established methods (scheme 21, page 32).

The second chapter of the thesis deals with the total synthesis of N-methyl secondine. Secodine and dehydrosecodine have been accepted as pivotal intermediates in the biosynthesis of indole alkaloids. The scarcities of general methods for the preparation of secodine have left this area in a primitive stage. During the course of this work a very general and flexible method has been developed for the synthesis of secodine. This is based on the generation of an indole-2-acrylate unit which makes use of Friedel Crafts acylation and wittig rections. The synthetic methodology developed during the course of this work would make the synthesis of dehydrosecondine systems much easier.

The third chapter of the text discussed the alkylation reactions of ketimine systems. The products of the reaction of N-isopropylidene cyclohexylamine with methyl acrylate have been studied by GC-MS analysis. It has been found that the major product is the B-aminoester (185) formed by the N-alkylation of cyclohexylamine which may be generated by a dimerisation elimination sequence followed by N-alkylation (Scheme 47). It is apparent from the above study that the reaction of ketimines withelectrophilic olefins is of rather limited utility as it does not result in the exclusive formation of a C-alkylated products as originally claimed 107 but rather is a very complex mixtureof reaction products as demonstrated by us.

The B-carboline nucleus forms an integral portion of many of the pharmacologically active compounds. B-carbolines have therefore been the subject of considerable synthetic efforts in indole chemistry. It is therefore of general interest to develop newapproaches to the B-carboline system as this would not only lead to simpler synthesis of B-Carboline alkaloids but also provide enteries to the more elaborately rearranged alkaloidal systems. The continuing interest of our group in this field have resulted in the development of several new methods for the synthesis of B-carbolines 128,129,131,132 the last chapter of this thesis describes an interesting cyclization of N-imidotryptamines using P2 S5 which results in the direct formation of the reduced B-carbooline lactams instead of the rather unstable vinylogius lactams obtnead on Bischler-Napieralski type cyclizatins using PICI3, PCI5 etc.

Download Full Thesis
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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
49.15 KB
2 1 The total synthesis of (+)-vincamine and (+)-eburnamonine 1
306.83 KB
3 2 The total synthesis of N-Methyl secondine 39
356.41 KB
4 3 Imine-enamine tautomerism-Nucleophilic reaction of imines 84
216.23 KB
5 4 A one step synthesis of B-Carbolines 115
140.45 KB
6 5 Experimental 135
16.77 KB
  5.1 General Notes 135
  5.2 The Total synthesis of (+)-vincamine and (+)-Eburanmonine 137
  5.3 The total syntghesis of N-Methyl secondine 145
  5.4 Imine-enamine tautomerism-Nucleophilic reaction of Imines 166
  5.5 A One step synthesis of B-Carbolones 169
7 6 References 174
284.82 KB
8 7 Publications 186
107.31 KB