Total synthesis of the hydroxyketone kurasoin A using asymmetric phase-transfer alkylation

  • J Org Chem. 2006 Oct 27;71(22):8651-4. doi: 10.1021/jo061395t.
Merritt B Andrus  1 ,  Erik J Hicken ,  Jeffrey C Stephens ,  D Karl Bedke
Affiliations
  • 1. Department of Chemistry and Biochemistry, Brigham Young University, C100 BNSN, Provo, Utah 84602-5700, USA. [email protected]
PMID: 17064051 DOI: 10.1021/jo061395t
Abstract

The total synthesis of the farnesyltransferase inhibitor kurasoin A has been achieved using a novel asymmetric phase-transfer-catalyzed glycolate alkylation reaction. 2,5-Dimethoxyacetophenone 7 with cinchonidinium catalyst 9(10 mol %) and hydroxide base with pivaloyl benzyl bromide 8 provided S-alkylation product 10 in high yield (80-99%) and excellent enantioselectivity. Baeyer-Villiger oxidation, Weinreb amide formation, and benzyl Grignard addition to the TES-ether 17 gave the protected target. Lithium hydroxide and peroxide generated kurasoin A ([alpha](D) +8.4 degrees ) without isomerization.

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