Evolution of a total synthesis of (-)-kendomycin exploiting a Petasis-Ferrier rearrangement/ring-closing olefin metathesis strategy

Amos B Smith 3rd; Eugen F Mesaros; Emmanuel A Meyer

doi:10.1021/ja060369+

Evolution of a total synthesis of (-)-kendomycin exploiting a Petasis-Ferrier rearrangement/ring-closing olefin metathesis strategy

J Am Chem Soc. 2006 Apr 19;128(15):5292-9. doi: 10.1021/ja060369+.

Authors

Amos B Smith 3rd¹, Eugen F Mesaros, Emmanuel A Meyer

Affiliation

¹ Department of Chemistry, Monell Chemical Senses Center, and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu

PMID: 16608366
DOI: 10.1021/ja060369+

Abstract

A convergent stereocontrolled total synthesis of (-)-kendomycin (1) has been achieved. The synthesis proceeds with a longest linear sequence of 21 steps, beginning with commercially available 2,4-dimethoxy-3-methylbenzaldehyde (12). Highlights of the synthesis include an effective Petasis-Ferrier union/rearrangement tactic to construct the sterically encumbered tetrahydropyran ring, a ring-closing metathesis to generate the C(4a-13-20a) macrocycle, an effective epoxidation/deoxygenation sequence to isomerize the C(13,14) olefin, and a biomimetic quinone-methide-lactol assembly to complete the synthesis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alkenes / chemistry*
Cyclization
Naphthoquinones
Rifabutin / analogs & derivatives*
Rifabutin / chemical synthesis

Substances

Alkenes
Naphthoquinones
kendomycin
sterekunthal A
Rifabutin

Grants and funding

GM-29028/GM/NIGMS NIH HHS/United States