Concise and highly stereoselective synthesis of the C20-C26 building block of halichondrins and Eribulin

Mingde Shan; Yoshito Kishi

doi:10.1021/ol203373d

Concise and highly stereoselective synthesis of the C20-C26 building block of halichondrins and Eribulin

Org Lett. 2012 Jan 20;14(2):660-3. doi: 10.1021/ol203373d. Epub 2012 Jan 11.

Authors

Mingde Shan¹, Yoshito Kishi

Affiliation

¹ Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.

PMID: 22236198
DOI: 10.1021/ol203373d

Abstract

A concise, stereoselective, and scalable synthesis of the C20-C26 building block of halichondrins and Eribulin is reported. The synthesis relies on three key transformations: regiospecific Ru-catalyzed intramolecular hydrosilylation, highly stereoselective S(N)2' substitution, and selective conversion of a C-Si to C-I bond. It is carried out in a 5-pot/4-workup operation without chromatographic purification, except for filtration through a silica-gel plug, to give the C20-C26 building block (dr > 200:1; ee > 99%) in ca. 60% overall yield from epoxide 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ethers, Cyclic / chemical synthesis*
Furans / chemical synthesis*
Ketones / chemical synthesis*
Macrolides
Molecular Structure
Stereoisomerism

Substances

Ethers, Cyclic
Furans
Ketones
Macrolides
halichondrin B
eribulin