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Synthesis 1996; 1996(6): 719-725
DOI: 10.1055/s-1996-4296
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The Dolastatins; 18: Stereospecific Synthesis of Dolaproine

George R. Pettit* , Douglas D. Burkett, Jószef Barkóczy, Gary L. Breneman, William E. Pettit
  • *Cancer Research Institute and Department of Chemistry, Arizona State University, Tempe, Arizona 85287-1604, USA, Fax +1(609)9658558
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Publication Date:
31 December 2000 (online)

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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.

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

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