A Biomimetically Inspired, Efficient Synthesis of the South 7 Hemisphere of Cephalostatin 7

Jong Seok Lee* and Philip L. Fuchs*
Department of Chemistry, 560 Oval Drive, Purdue University, West Lafayette, Indiana 47907
J. Am. Chem. Soc., 2005, 127 (38), pp 13122–13123
DOI: 10.1021/ja0531935
Publication Date (Web): September 3, 2005
Copyright © 2005 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.

, pfuchs@purdue.edu

Abstract

Abstract Image

Synthesis of the South 7 hemisphere of cephalostatin 7 is described applying a second-generation synthetic strategy, which retains all the existing carbons in hecogenin acetate 1. TFAT (trifluoroacetyl trifluoromethanesulfonate)-assisted E-ring opening yields the key D-ring cyclopentadiene. A facially selective [4 + 2] cycloaddition between a series of steroidal D-ring dienes and singlet oxygen was conformationally directed by the C21-Me stereochemistry of the side chain. Sharpless asymmetric dihydroxylation of the terminal olefin provides (S)-C25-OH. An acid-catalyzed SN2‘ intramolecular alkylation of an acetal oxygen was followed by a one-pot sequence of β-elimination and spiroketalization. The new route provides a practical 16-operation synthesis of the South 7 hemisphere (20% overall), as well as a model for construction of the crucial North 1 hemisphere.

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History

  • Published In Issue September 28, 2005
  • Received May 16, 2005

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