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Article

Syntheses of the Eastern Halves of Ritterazines B, F, G, and H, Leading to Reassignment of the 5,5-Spiroketal Stereochemistry of Ritterazines B and F

Supporting Info

Scott T. Phillips and Matthew D. Shair*

Contribution from the Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts 02138

J. Am. Chem. Soc., 2007, 129 (20), pp 6589–6598

DOI: 10.1021/ja0705487

Publication Date (Web): May 1, 2007

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

, shair@chemistry.harvard.edu

Abstract

The ritterazine class of natural products comprises 26 compoundsall of which are spiroketal-containing steroidal heterodimersthat inhibit the proliferation of cultured human cancer cell lines with IC₅₀ values in the low nanomolar range. Little is known about their chemistry, cellular target(s), or mechanism(s) of growth inhibition, due primarily to the small amount of material available from natural sources. In this paper we report syntheses of the eastern halves of ritterazines B, F, G, and H and address the energetic and mechanistic aspects of spiroketal equilibration for each. These studies have led to reassignment of the 5,5-spiroketal stereochemistry of ritterazines B and F, and they have enabled us to propose a quantitative description of the natural distribution of these ritterazine compounds.