Stereoselective Total Syntheses of the Antitumor Antibiotics (+)-Actinobolin and (-)-Bactobolin from a Common Bridged Lactone Intermediate

Ravi S. Garigipati, David M. Tschaen, Steven M. Weinreb

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Efficient, highly stereoselective approaches have been developed to (+)-actinobolin (1) and (-)-bactobolin (3) from bridged α-keto lactone 11, which can be readily prepared via intramolecular SnCl4 catalyzed ene reaction of cyclohexenol glyoxylate (5). A novel method has been developed for direct, stereoselective reductive sulfonamidation of 11 to simultaneously introduce a protected C-4 amino group of the natural products and generate the C-4/4a relative stereochemistry. It was found that a PMS ((p-methylbenzyl)sulfonyl) nitrogen protecting group was useful in the actinobolin synthesis, but for bactobolin the SES ((β-(trimethylsilyl)ethyl)sulfonyl) group was necessary. The C-3 substitution and stereochemistry of the antibiotics was established by manipulation of the carbonyl group of the bridged lactone intermediates, and in particular, a novel organocerium reagent was applied to this part of the bactobolin synthesis (cf. 35 → 37). In both syntheses an unprecedented intramolecular enolate C-acylation was used to prepare the bicyclic enol lactone systems.

Original languageEnglish (US)
Pages (from-to)3475-3482
Number of pages8
JournalJournal of the American Chemical Society
Volume112
Issue number9
DOIs
StatePublished - Jan 1 1990

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Lactones
Antibiotics
Stereochemistry
Anti-Bacterial Agents
Acylation
Biological Products
Substitution reactions
Nitrogen
bactobolin
actinobolin

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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title = "Stereoselective Total Syntheses of the Antitumor Antibiotics (+)-Actinobolin and (-)-Bactobolin from a Common Bridged Lactone Intermediate",
abstract = "Efficient, highly stereoselective approaches have been developed to (+)-actinobolin (1) and (-)-bactobolin (3) from bridged α-keto lactone 11, which can be readily prepared via intramolecular SnCl4 catalyzed ene reaction of cyclohexenol glyoxylate (5). A novel method has been developed for direct, stereoselective reductive sulfonamidation of 11 to simultaneously introduce a protected C-4 amino group of the natural products and generate the C-4/4a relative stereochemistry. It was found that a PMS ((p-methylbenzyl)sulfonyl) nitrogen protecting group was useful in the actinobolin synthesis, but for bactobolin the SES ((β-(trimethylsilyl)ethyl)sulfonyl) group was necessary. The C-3 substitution and stereochemistry of the antibiotics was established by manipulation of the carbonyl group of the bridged lactone intermediates, and in particular, a novel organocerium reagent was applied to this part of the bactobolin synthesis (cf. 35 → 37). In both syntheses an unprecedented intramolecular enolate C-acylation was used to prepare the bicyclic enol lactone systems.",
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Stereoselective Total Syntheses of the Antitumor Antibiotics (+)-Actinobolin and (-)-Bactobolin from a Common Bridged Lactone Intermediate. / Garigipati, Ravi S.; Tschaen, David M.; Weinreb, Steven M.

In: Journal of the American Chemical Society, Vol. 112, No. 9, 01.01.1990, p. 3475-3482.

Research output: Contribution to journalArticle

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