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Chemoenzymatic approaches to SCH 56592, a new azole antifungal
Author(s) -
Morgan Brian,
Stockwell Brent R.,
Dodds David R.,
Andrews David R.,
Sudhakar Anantha R.,
Nielsen Christopher M.,
Mergelsberg Ingrid,
Zumbach Arne
Publication year - 1997
Publication title -
journal of the american oil chemists' society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.512
H-Index - 117
eISSN - 1558-9331
pISSN - 0003-021X
DOI - 10.1007/s11746-997-0238-2
Subject(s) - candida rugosa , acylation , chemistry , diastereomer , enzyme , selectivity , stereochemistry , reactivity (psychology) , azole , hydrolysis , lipase , antifungal , organic chemistry , biology , microbiology and biotechnology , catalysis , medicine , alternative medicine , pathology
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.