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PMID: 19249829 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

An aldol-based synthesis of (+)-peloruside a, a potent microtubule stabilizing agent.

Journal of the American Chemical Society ·Vol. 131 ·No. 11 ·2009-03-25 ·Pages 3840-1

Evans DA, Welch DS, Speed AW, Moniz GA, Reichelt A, Ho S

Abstract

A convergent synthesis of the marine natural product (+)-peloruside has been reported. This target has been assembled through the successive application of two methyl ketone boron aldol addition reactions to the latent C(7)-C(11) dialdehyde synthon. This approach afforded a 22-step synthesis of this natural product. The influence of resident stereocenters on aldol reaction diastereoselection has been examined in detail.

MeSH Terms

Alcohols Aldehydes Animals Biological Products/chemical synthesis Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis Lactones/chemical synthesis Porifera/chemistry Stereoisomerism Tubulin Modulators/chemical synthesis

Chemicals

Alcohols Aldehydes Biological Products Bridged Bicyclo Compounds, Heterocyclic Lactones Tubulin Modulators peloruside A

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Evans David A

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. evans@chemistry.harvard.edu

Welch Dennie S

Speed Alexander W H

Moniz George A

Reichelt Andreas

Ho Stephen

References (10)

10 references, click to expand

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Toward the synthesis of peloruside a: fragment synthesis and coupling studies.
Org Lett. 2003 Feb 20;5(4):599-602 PMID: 12583779
Enantioselective total synthesis of peloruside A: a potent microtubule stabilizer.
Org Lett. 2008 Mar 6;10(5):1001-4 PMID: 18247632
Toward a total synthesis of peloruside A: enantioselective preparation of the C8-C19 region.
Org Lett. 2003 Dec 25;5(26):4959-61 PMID: 14682739
Total synthesis and absolute configuration of the novel microtubule-stabilizing agent peloruside A.
Angew Chem Int Ed Engl. 2003 Apr 11;42(14):1648-52 PMID: 12698467
Asymmetric induction in methyl ketone aldol additions to alpha-alkoxy and alpha,beta-bisalkoxy aldehydes: a model for acyclic stereocontrol.
J Am Chem Soc. 2006 Jul 26;128(29):9433-41 PMID: 16848480
Total synthesis of (+)-peloruside A.
Org Lett. 2005 Mar 31;7(7):1303-5 PMID: 15787492
Stereoselective synthesis of the C(1)-C(11) fragment of peloruside A.
Org Lett. 2005 Sep 1;7(18):3941-4 PMID: 16119937
1,5-asymmetric induction in boron-mediated beta-alkoxy methyl ketone aldol addition reactions.
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Article Info

Journal

Journal of the American Chemical Society

Abbr.

J Am Chem Soc

ISSN

1520-5126

DOI

10.1021/ja900020a

evans@chemistry.harvard.edu

Published

2009-03-25

Pages

3840-1

Language

English

Region

United States

NLM ID

7503056

PMCID

PMC3357919

Subset

Grants

NIGMS NIH HHS · R01 GM033328 · United States

NIGMS NIH HHS · R01 GM081546 · United States

NIGMS NIH HHS · R01 GM081546-04 · United States

NIGMS NIH HHS · 5R01-GM081546-01 · United States

External Links

PubMed source DOI: 10.1021/ja900020a PMC Full Text View journal details

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An aldol-based synthesis of (+)-peloruside a, a potent microtubule stabilizing agent.

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