The dolastatins; 18: Stereospecific synthesis of dolaproine

George Pettit, Douglas D. Burkett, József Barkóczy, Gary L. Breneman, William E. Pettit

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Dolastatin 10 (1), isolated from the sea hare Dolabella auricularia, has proved to be an exceptionally promising antineoplastic substance. Synthesis of this new and important peptide has been achieved. However, a more convenient and stereoselective synthesis of its three chiral center dolaproine (2a) unit has become necessary. A practical solution to this challenging problem was realized by employment of the following key reaction steps. Chiral oxazolidinone 5 was condensed at -75°C with S-prolinal 4 using dibutylboron triflate to direct the stereochemical course of the aldol reaction. Methylation of the product (6, 60-80% yields) and cleavage of the amide, in 83 and 93% yields respectively, completed a facile route to N-Boc-dolaproine (2b). Pertinent aspects of the aldol reaction and cleavage of oxazolidinone amides are discussed.

Original languageEnglish (US)
Pages (from-to)719-725
Number of pages7
JournalSynthesis
Issue number6
DOIs
StatePublished - 1996

Keywords

  • antineoplastic peptide
  • chiral oxazolidinone
  • dolastatin 10
  • stereospecific aldol reaction

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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    Pettit, G., Burkett, D. D., Barkóczy, J., Breneman, G. L., & Pettit, W. E. (1996). The dolastatins; 18: Stereospecific synthesis of dolaproine. Synthesis, (6), 719-725. https://doi.org/10.1055/s-1996-4296