Asymmetric crotylation reactions in synthesis of polypropionate-derived macrolides: Application to total synthesis of oleandolide

Tao Hu, Norito Takenaka, James S. Panek

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Complete details of a convergent asymmetric synthesis of oleandolide (1), the aglycon of the macrolide antibiotic oleandomycin, is described. The synthesis has been achieved through the assembly and coupling of the left- and right-hand subunits 12 and 38, respectively. These subunits were prepared from chiral silane-based asymmetric crotylation reactions to control the stereochemical relationships. The left- and right-hand subunits (C1-C7 and C8-C14) were brought together through a Pd(0)-catalyzed sp3-sp2 cross-coupling reaction between the zinc intermediate 40 and vinyl triflate 38 to give 27. This product was converted to seco acid 42a and cyclized to lactone 35 under Yamaguchi conditions. This material was then epoxidized with m-chloroperbenzoic acid (m-CPBA) to install the correct C8 epoxide as a single diastereomer, which after a short deprotection sequence completed the synthesis of oleandolide.

Original languageEnglish (US)
Pages (from-to)12806-12815
Number of pages10
JournalJournal of the American Chemical Society
Volume124
Issue number43
DOIs
StatePublished - Oct 30 2002
Externally publishedYes

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Macrolides
Hand
Oleandomycin
Silanes
Epoxy Compounds
Cross Reactions
Lactones
Zinc
Acids
Antibiotics
Anti-Bacterial Agents
oleandolide
3-chloroperbenzoic acid
vinyl triflate

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Asymmetric crotylation reactions in synthesis of polypropionate-derived macrolides : Application to total synthesis of oleandolide. / Hu, Tao; Takenaka, Norito; Panek, James S.

In: Journal of the American Chemical Society, Vol. 124, No. 43, 30.10.2002, p. 12806-12815.

Research output: Contribution to journalArticle

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N2 - Complete details of a convergent asymmetric synthesis of oleandolide (1), the aglycon of the macrolide antibiotic oleandomycin, is described. The synthesis has been achieved through the assembly and coupling of the left- and right-hand subunits 12 and 38, respectively. These subunits were prepared from chiral silane-based asymmetric crotylation reactions to control the stereochemical relationships. The left- and right-hand subunits (C1-C7 and C8-C14) were brought together through a Pd(0)-catalyzed sp3-sp2 cross-coupling reaction between the zinc intermediate 40 and vinyl triflate 38 to give 27. This product was converted to seco acid 42a and cyclized to lactone 35 under Yamaguchi conditions. This material was then epoxidized with m-chloroperbenzoic acid (m-CPBA) to install the correct C8 epoxide as a single diastereomer, which after a short deprotection sequence completed the synthesis of oleandolide.

AB - Complete details of a convergent asymmetric synthesis of oleandolide (1), the aglycon of the macrolide antibiotic oleandomycin, is described. The synthesis has been achieved through the assembly and coupling of the left- and right-hand subunits 12 and 38, respectively. These subunits were prepared from chiral silane-based asymmetric crotylation reactions to control the stereochemical relationships. The left- and right-hand subunits (C1-C7 and C8-C14) were brought together through a Pd(0)-catalyzed sp3-sp2 cross-coupling reaction between the zinc intermediate 40 and vinyl triflate 38 to give 27. This product was converted to seco acid 42a and cyclized to lactone 35 under Yamaguchi conditions. This material was then epoxidized with m-chloroperbenzoic acid (m-CPBA) to install the correct C8 epoxide as a single diastereomer, which after a short deprotection sequence completed the synthesis of oleandolide.

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