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Chemoenzymatic approaches to SCH 56592, a new azole antifungal

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Journal of the American Oil Chemists' Society

Abstract

Chemoenzymatic approaches to the synthesis of two key chiral-precursors of a new azole antifungal agent, SCH 56592, are described. In particular, the enzymatic diastereoselective acylation of 2-benzyloxy-3-pentanol (7) was developed to produce (2S;3R)-7 in >97% diastereomeric excess (de) from otherwise unusable mixtures of (2S,3R)/(2S,3S)-7 (40–80% de). The selectivity and reactivity of commercially available Candida rugosa and Mucor miehei lipases are compared for the acylation of 7 and the hydrolysis of the corresponding butyrate 16a. Of the 17 C. rugosa enzyme preparations that were examined for acylation of 7, two purified enzyme preparations showed no reactivity, five enzymes showed high diastereoselectivity with preference for the (2S,3R)-isomer, and seven showed a slight preference for the (2S,3S)-isomer.

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Authors and Affiliations

  1. Chemical Process R & D, 07083, Union, New Jersey

    David R. Andrews, Anantha R. Sudhakar & Christopher M. Nielsen

  2. Werthenstein Chemie AG, CH-6105, Schachen, Switzerland

    Ingrid Mergelsberg & Arne Zumbach

  3. Schering-Plough Research Institute, Biotransformations Group, K-15-1/1800, 2015 Galloping Hill Road, 07033-0539, Kenilworth, NJ

    Brian Morgan, Brent R. Stockwell & David R. Dodds

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  1. Brian Morgan
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  2. Brent R. Stockwell
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  3. David R. Dodds
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Correspondence to Brian Morgan.

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Morgan, B., Stockwell, B.R., Dodds, D.R. et al. Chemoenzymatic approaches to SCH 56592, a new azole antifungal. J Amer Oil Chem Soc 74, 1361–1370 (1997). https://doi.org/10.1007/s11746-997-0238-2

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  • DOI: https://doi.org/10.1007/s11746-997-0238-2

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