The studies toward synthesis of cephalostatin

You Pan, Purdue University

Abstract

The synthesis of a series of analogs of cephalostatins are reported. All of the analogs contain two symmetric steroidal unites combined with a pyrazine ring at C-2 and C-3 positions. The synthetic strategy included bromination of 3-oxo-steroids, followed by azidation to form 2-azido-3-oxo-steroids. The 2-azido-3-oxo-steroids were reduced to 2-amino-3-oxo-steroids which underwent condensation and oxidation spontaneously to afford the pyrazines as final products. This strategy provides a simple and efficient pathway to synthesize symmetric steroidal pyrazines. The various steroidal moieties are 5$\alpha$-cholestan-3-one, 17-hydroxy-5$\alpha$-androstan-3-one, 5$\alpha$-androstane-3,17-dione, (25R)-12$\beta$-hydroxy-5$\alpha$-spirostane-3,11-dione, and their derivatives. During the sequence two novel compounds were isolated. Their structures and the mechanism of their formation are discussed. The studies toward synthesis of the unsymmetric pyrazine which included using Staudinger reaction approach, N-alkylation, $\alpha$-halo oxime and $\alpha$-azido oxime methods, are described.

Degree

Ph.D.

Advisors

Fuchs, Purdue University.

Subject Area

Organic chemistry

COinS