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Synlett 1997; 1997(12): 1438-1440
DOI: 10.1055/s-1997-1065
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Conjugate Addition of Trimethylsilylmethyl Cuprates to Artemisinic Acid: Homologation and Subsequent Conversion to 9β-Modified Artemisinin Analogs

Jeffrey A. Vroman1 , Iklas Khan2 , Mitchell A. Avery3
  • 1Department of Medicinal Chemistry, School of Pharmacy; University of Mississippi, University, MS 38677
  • 2National Center for Development of Natural Products; University of Mississippi, University, MS 38677
  • 3Department of Chemistry; University of Mississippi, University, MS 38677
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Publication History

Publication Date:
31 December 2000 (online)

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Conjugate addition to the acrylic acid moiety of artemisinic acid 2 was made possible by in situ protection as a silyl ester followed by treatment with a trimethylsilylmethyl cuprate such as (TMSCH2)C4H9CuLi•LiX, where X = CN or I. After deprotective workup, the homologated carboxylic acid 9 was obtained in excellent yields. Photoxygenation and acid treatment of 9 then led to the facile preparation of potent 9β-modified analogs of the naturally occurring antimalarial agent, artemisinin.

conjugate addition - trimethylsilylmethyl cuprate - carboxylic acid - transient silyl ester