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Synthesis 2001(13): 1989-1992
DOI: 10.1055/s-2001-17711
PAPER
© Georg Thieme Verlag Stuttgart · New York

Chemoenzymatic Synthesis of All Four Cytoxazone Stereoisomers

Zdenko Hameršaka, Edina Ljubovića, Mladen Merćepb, Milan Mesićb, Vitomir Šunjić*a
a Ruđer Bošković Institute, P.O.B. 180, HR-10002, Zagreb, Croatia
b PLIVA d.d., Research Institute, Prilaz baruna FilipoviĘa 25, HR-10000, Zagreb, Croatia
Fax: +385(1)4680195; e-Mail: sunjic@rudjer.irb.hr;
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Publication History

Received 6 April 2001
Publication Date:
11 August 2004 (online)

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Abstract

Racemic cytoxazone (±-5) was synthesized starting from easily available glycidic ester (±)-1 by nucleophilic epoxide ring opening, followed by 2-oxazolidinone ring construction and calcium chloride/sodium borohydride reduction of the intermediary ester (±)-4. Kinetic resolution of (±)-5 performed by acetylation with vinyl acetate catalyzed by Penicillium camemberti lipase (PcamL) afforded, on hydrolysis of acetate (-)-6, cytoxazone (-)-5 in 33% overall yield and 88.2% enantiomeric excess (ee), and its enantiomer (+)-5 (38% yield, 89.3% ee). Base-catalyzed epimerization of intermediary (±)-4 to (±)-7, and reduction and kinetic resolution with Candida antarctica lipase (CAL) led to epi-cytoxazones (-)-8 and (+)-8.

Key words

oxazolidinones - epoxide ring opening - lipases - kinetic resolution