Total synthesis of (+)-schweinfurthins B and E

Joseph J. Topczewski, Jeffrey Neighbors, David F. Wiemer

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

(Chemical Equation Presented) The first total synthesis of (+)-schweinfurthin B, a potent and differentially active cytotoxic agent, has been accomplished. Completion of the synthesis required just 16 steps in the longest linear sequence from commercially available vanillin. Key synthetic transformations included a Shi epoxidation and an efficient cascade cyclization initiated by treatment of the resulting epoxide with BF3· OEt2. Furthermore, use of a methyl ether as a stable protecting group for benzylic alcohols dramatically increased the efficiency of the overall sequence. The benzylic ether can be removed from this electron-rich aromatic system through oxidation with DDQ that provided the desired aldehyde intermediate in quantitative yield and shortened the synthetic sequence. Introduction of the A-ring diol in the required cis stereochemistry then became viable through a short sequence highlighted by an aldol condensation with benzaldehyde to introduce an olefin as a latent carbonyl group at the C-3 position. This synthesis established for the first time the absolute stereochemistry of the natural product, and provides access to material on a scale that will advance biological studies. The total synthesis of the closely related compound (+)-schweinfurthin E also is reported.

Original languageEnglish (US)
Pages (from-to)6965-6972
Number of pages8
JournalJournal of Organic Chemistry
Volume74
Issue number18
DOIs
StatePublished - Sep 18 2009

Fingerprint

Stereochemistry
Methyl Ethers
Epoxidation
Cyclization
Epoxy Compounds
Cytotoxins
Alkenes
Biological Products
Aldehydes
Ether
Condensation
Alcohols
Oxidation
schweinfurthin E
schweinfurthin B
Electrons
benzaldehyde
3-hydroxybutanal
vanillin

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

Topczewski, Joseph J. ; Neighbors, Jeffrey ; Wiemer, David F. / Total synthesis of (+)-schweinfurthins B and E. In: Journal of Organic Chemistry. 2009 ; Vol. 74, No. 18. pp. 6965-6972.
@article{4f1531c99a4c4a46858804c79f998a33,
title = "Total synthesis of (+)-schweinfurthins B and E",
abstract = "(Chemical Equation Presented) The first total synthesis of (+)-schweinfurthin B, a potent and differentially active cytotoxic agent, has been accomplished. Completion of the synthesis required just 16 steps in the longest linear sequence from commercially available vanillin. Key synthetic transformations included a Shi epoxidation and an efficient cascade cyclization initiated by treatment of the resulting epoxide with BF3· OEt2. Furthermore, use of a methyl ether as a stable protecting group for benzylic alcohols dramatically increased the efficiency of the overall sequence. The benzylic ether can be removed from this electron-rich aromatic system through oxidation with DDQ that provided the desired aldehyde intermediate in quantitative yield and shortened the synthetic sequence. Introduction of the A-ring diol in the required cis stereochemistry then became viable through a short sequence highlighted by an aldol condensation with benzaldehyde to introduce an olefin as a latent carbonyl group at the C-3 position. This synthesis established for the first time the absolute stereochemistry of the natural product, and provides access to material on a scale that will advance biological studies. The total synthesis of the closely related compound (+)-schweinfurthin E also is reported.",
author = "Topczewski, {Joseph J.} and Jeffrey Neighbors and Wiemer, {David F.}",
year = "2009",
month = "9",
day = "18",
doi = "10.1021/jo901161m",
language = "English (US)",
volume = "74",
pages = "6965--6972",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "18",

}

Total synthesis of (+)-schweinfurthins B and E. / Topczewski, Joseph J.; Neighbors, Jeffrey; Wiemer, David F.

In: Journal of Organic Chemistry, Vol. 74, No. 18, 18.09.2009, p. 6965-6972.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Total synthesis of (+)-schweinfurthins B and E

AU - Topczewski, Joseph J.

AU - Neighbors, Jeffrey

AU - Wiemer, David F.

PY - 2009/9/18

Y1 - 2009/9/18

N2 - (Chemical Equation Presented) The first total synthesis of (+)-schweinfurthin B, a potent and differentially active cytotoxic agent, has been accomplished. Completion of the synthesis required just 16 steps in the longest linear sequence from commercially available vanillin. Key synthetic transformations included a Shi epoxidation and an efficient cascade cyclization initiated by treatment of the resulting epoxide with BF3· OEt2. Furthermore, use of a methyl ether as a stable protecting group for benzylic alcohols dramatically increased the efficiency of the overall sequence. The benzylic ether can be removed from this electron-rich aromatic system through oxidation with DDQ that provided the desired aldehyde intermediate in quantitative yield and shortened the synthetic sequence. Introduction of the A-ring diol in the required cis stereochemistry then became viable through a short sequence highlighted by an aldol condensation with benzaldehyde to introduce an olefin as a latent carbonyl group at the C-3 position. This synthesis established for the first time the absolute stereochemistry of the natural product, and provides access to material on a scale that will advance biological studies. The total synthesis of the closely related compound (+)-schweinfurthin E also is reported.

AB - (Chemical Equation Presented) The first total synthesis of (+)-schweinfurthin B, a potent and differentially active cytotoxic agent, has been accomplished. Completion of the synthesis required just 16 steps in the longest linear sequence from commercially available vanillin. Key synthetic transformations included a Shi epoxidation and an efficient cascade cyclization initiated by treatment of the resulting epoxide with BF3· OEt2. Furthermore, use of a methyl ether as a stable protecting group for benzylic alcohols dramatically increased the efficiency of the overall sequence. The benzylic ether can be removed from this electron-rich aromatic system through oxidation with DDQ that provided the desired aldehyde intermediate in quantitative yield and shortened the synthetic sequence. Introduction of the A-ring diol in the required cis stereochemistry then became viable through a short sequence highlighted by an aldol condensation with benzaldehyde to introduce an olefin as a latent carbonyl group at the C-3 position. This synthesis established for the first time the absolute stereochemistry of the natural product, and provides access to material on a scale that will advance biological studies. The total synthesis of the closely related compound (+)-schweinfurthin E also is reported.

UR - http://www.scopus.com/inward/record.url?scp=70249107854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70249107854&partnerID=8YFLogxK

U2 - 10.1021/jo901161m

DO - 10.1021/jo901161m

M3 - Article

VL - 74

SP - 6965

EP - 6972

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 18

ER -