A practical and efficient synthesis of the C-16-C-28 spiroketal fragment (CD) of the spongistatins

Matthew J Gaunt; David F Hook; Huw R Tanner; Steven V Ley

doi:10.1021/ol035848h

A practical and efficient synthesis of the C-16-C-28 spiroketal fragment (CD) of the spongistatins

Org Lett. 2003 Dec 11;5(25):4815-8. doi: 10.1021/ol035848h.

Authors

Matthew J Gaunt¹, David F Hook, Huw R Tanner, Steven V Ley

Affiliation

¹ Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.

PMID: 14653681
DOI: 10.1021/ol035848h

Abstract

A practical and efficient route to the CD spiroketal (C-16-C-28) of the spongistatins is reported. Two stereocenters are introduced from chiral building blocks with the remainder introduced by substrate-controlled transformations. The key beta-keto-1,3-dithiane intermediate is generated by a dithiol conjugate addition to an ynone and the 1,3-dithiane unit in the C-ring plays a key role in the spiroketalization and subsequent epimerization. The synthesis requires 24 steps, with a longest linear sequence of 19 steps in an overall yield of 14.5% (for the longest linear sequence). [reaction: see text]