Synthesis of the C29−C44 Portion of Spongistatin 1 (Altohyrtin A)

Grier A. Wallace, Robert W. Scott, and Clayton H. Heathcock*
Department of Chemistry, University of California, Berkeley, California 94720
J. Org. Chem., 2000, 65 (13), pp 4145–4152
DOI: 10.1021/jo0002801
Publication Date (Web): June 2, 2000
Copyright © 2000 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, heathcock@cchem.berkeley.edu

Abstract

Abstract Image

Two synthetic approaches to the C29−C44 portion of spongistatin 1 (altohyritin A) have been developed. The key step of the first approach relies on the Claisen rearrangement of glucal 18 to provide ester 20a. This intermediate was advanced to silyl enol ether 30, which was coupled under Mukaiyama aldol conditions with aldehyde 3. Cyclization of this aldol adduct completed our first synthesis of the C29−C44 portion of spongistatin 1, requiring 25 total steps and occurring in 2.4% yield over the longest linear sequence (21 steps). We have also developed a second-generation approach based on the C-glycosidation of glucal 43. Through equilibration of the corresponding C-glycosides 49a/b and 50a/b the desired C-glycoside (50a) was obtained in good yield. Aldol condensation of this ketone provided cyclization precursor 67, which undergoes acid-catalyzed ketalization to close the E-ring of the spongistatins. An oxidation/reduction protocol was employed to set the C37 stereocenter. Protection of the C37 carbonol and selective unmasking of the C44 carbonol completed our second generation synthesis. This approach requires 27 steps and occurred in 13.2% yield over the longest linear sequence (18 steps).

View: Full Text HTML | Hi-Res PDF

Tools

History

  • Published In Issue June 30, 2000
  • Received February 29, 2000

Recommend & Share

Related Content

Other ACS content by these authors: