Synthetic studies toward the total synthesis of Cephalostatin 12

Seongkon Kim, Purdue University

Abstract

Synthetic efforts toward the total synthesis of the Cepalostatin are described. The key chemical transformations involved are: (1) reductive cleavage of bromoepoxide 2.6 using ultrasonicated Zinc/Copper couple to install the C-17 hydroxyl moiety; (2) the Reich iodoso syn-elimination of iodide 2.26 to establish the highly functionalized steroid D-ring oxidation pattern; (3) the elaboration of the dihydrofuran E-ring by way of an intramolecular Wadsworth-Emmons reaction of $\alpha$-phosphonate ester 1.32 and establishment of the C-25 stereochemistry using the Corey double stereodifferentiation osmylation of 3.21. NBS-mediated cyclization of 3.22 gave cleanly the C-20 brominated 5/5 spiroketal 4.13 establishing all the stereochemistry required for North spiroketal of cephalostatin except for the C-20 center. After much experimentation, it was discovered that CrCl$\sb2$ mediated dehalogenation cleanly afforded the reduced product 4.3 having the unnatural stereochemistry. Attempts to find conditions giving the natural stereochemistry at C-20 were unsuccessful. These difficulties point out the need for another type of reduction method or a different strategy. Seperate projects which were not included in this thesis are as follows: (1) Generation of new type of radical ($\alpha$-heteroatom substituted radical) to give pyran and its application to complex molecules. (2) Development of new synthetic methology using silicon and tin chemistry for the concise synthesis of highly oxgenated substrates (see PUBLICATIONS).

Degree

Ph.D.

Advisors

Fuchs, Purdue University.

Subject Area

Organic chemistry

COinS