Chemoenzymatic Synthesis of All Four Cytoxazone Stereoisomers
2001; Thieme Medical Publishers (Germany); Volume: 2001; Issue: 13 Linguagem: Inglês
10.1055/s-2001-17711
ISSN1437-210X
AutoresZdenko Hameršak, Edina Ljubović, Mladen Merćep, Milan Mesić, Vitomir Šunjić,
Tópico(s)Microbial Metabolic Engineering and Bioproduction
ResumoRacemic 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.
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