Total synthesis of (+)-phorboxazole A exploiting the Petasis-Ferrier rearrangement

A B Smith 3rd; K P Minbiole; P R Verhoest; M Schelhaas

doi:10.1021/ja011604l

Total synthesis of (+)-phorboxazole A exploiting the Petasis-Ferrier rearrangement

J Am Chem Soc. 2001 Nov 7;123(44):10942-53. doi: 10.1021/ja011604l.

Authors

A B Smith 3rd¹, K P Minbiole, P R Verhoest, M Schelhaas

Affiliation

¹ Department of Chemistry, Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, PA 19104, USA.

PMID: 11686698
DOI: 10.1021/ja011604l

Abstract

A highly convergent, stereocontrolled total synthesis of the potent antiproliferative agent (+)-phorboxazole A (1) has been achieved. Highlights of the synthesis include: modified Petasis-Ferrier rearrangements for assembly of both the C(11-15) and C(22-26) cis-tetrahydropyran rings; extension of the Julia olefination to the synthesis of enol ethers; the design, synthesis, and application of a novel bifunctional oxazole linchpin; and Stille coupling of a C(28) trimethyl stannane with a C(29) oxazole triflate. The longest linear sequence leading to (+)-phorboxazole A (1) was 27 steps, with an overall yield of 3%.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis*
Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
Oxazoles / chemical synthesis*
Stereoisomerism

Substances

Antineoplastic Agents
Heterocyclic Compounds, 4 or More Rings
Oxazoles
phorboxazole A

Grants and funding

CA-19033/CA/NCI NIH HHS/United States