The synthesis of the A-ring of taxol.
Item
-
Title
-
The synthesis of the A-ring of taxol.
-
Identifier
-
AAI9417464
-
identifier
-
9417464
-
Creator
-
Gao, Zhongli.
-
Contributor
-
Adviser: W. F. Berkowitz
-
Date
-
1994
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Chemistry, Organic | Chemistry, Pharmaceutical
-
Abstract
-
Synthesis of the tetracyclic portion of taxol from simple precursors has the potential not only for providing an alternative source of this drug, and a second generation of drugs with enhanced attributes, but also for defining the portions of molecule responsible for its biological activity. In our attempts at total synthesis of taxol via a photochemical approach, eg. connecting an A-ring synthon with a CD-ring portion, we needed a useful A-ring synthon. The focus of this investigation was directed toward the synthesis of an A-ring synthon for taxol.;The synthesis started from the Johnson-Claisen rearrangement reaction of 3-methyl-2-buten-1-ol to afford, after hydrolysis, 3,3-dimethyl-4-pentenoic acid. This acid was esterified with 2-methyl-2-buten-1-ol. The resulting ester was subjected to the Ireland-Claisen rearrangement conditions and esterification to form a diene ester. This diene ester and its derivatives have also been synthesized via two other routes. Ozonolysis of the diene ester yielded a ketoaldehyde. This ketoaldehyde underwent an intramolecular aldol reaction catalyzed by (L)-proline to yield an A-ring synthon with the proper functionalities for further transformation. The further transformation was attempted by protection of the keto functionality as a ketal and oxidation of the hydroxyl group into a keto group to obtain a key intermediate keto ester. Addition of an acetyl equivalent was attempted by acetylene addition-hydration.;Meanwhile, the diene ester was reduced into an alcohol and protected as a silyl ether. After ozonolysis and aldol cyclization, another A-ring synthon was obtained successfully. This and the intermediate obtained above are both suitable for the further transformation and will be employed in the construction of the A-ring synthon of taxol.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
