Total synthesis of the antitumor macrolide, rhizoxin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The first total synthesis of the antitumor macrolide rhizoxin in a highly stereocontrolled manner has been achieved. The efficient construction of optically pure key building fragments designed based on rational retrosynthetic analysis was accomplished in a concise manner. Synthesis of the Right-Wing started from the chiral half-ester generated by asymmetric hydrolysis of the corresponding meso-dieester using pig liver esterase. The remaining chiral centers of the fragment were constructed by cyclic hydroboration. Synthesis of the Left-Wing was accomplished starting from methyl (S)-3-hydroxy-2-methylpropionate which in turn had been prepared again by enzyme mediated transformation. Coupling of Right-Wing and Left-Wing was carried out by Julia condensation, and the macrocylic lactone was constructed by intramolecular Horner-Emmons reaction. Finally, the stereoselective epoxidation was achieved cleanly after formation of unsaturated 16-membered macrocylic lactone. Chromophore-side-chain moiety was constructed at final stage by reaction of the phosphineoxide in 80% yield with high selectivity (E/Z = >20/1). The present methodology will be useful for the synthesis of the homologues or man-made rhizoxins.

Original languageEnglish
Pages (from-to)122-137
Number of pages16
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume53
Issue number2
Publication statusPublished - 1995 Feb
Externally publishedYes

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Macrolides
Lactones
Epoxidation
Esterases
Chromophores
Liver
Condensation
Hydrolysis
Esters
rhizoxin
Enzymes

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Total synthesis of the antitumor macrolide, rhizoxin. / Nakada, Masahisa.

In: Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, Vol. 53, No. 2, 02.1995, p. 122-137.

Research output: Contribution to journalArticle

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