Baeyer-Villiger monooxygenase-catalyzed desymmetrizations of cyclobutanones. Application to the synthesis of valuable spirolactones

TETRAHEDRON

卷:72

Article; Proceedings Paper

Rodriguez-Mata, Maria¹  Lavandera, Ivan¹  Gotor-Fernandez, Vicente¹  Gotor, Vicente¹  Garcia-Cerrada, Susana²  Mendiola, Javier²  de Frutos, Oscar²  Collado, Ivan² 

[1] Univ Oviedo, Dept Quim Organ & Inorgan, Inst Univ Biotecnol Asturias, C Julian Claveria 8, E-33006 Oviedo, Spain

[2] Ctr Invest Lilly SA, Avda Ind 30, Madrid 28108, Spain

关键词: Asymmetric synthesis;    Baeyer-Villiger oxidation;    Lactones;    Oxygenases;    Spiro compounds;   

DOI  :  10.1016/j.tet.2015.12.071

来源: Elsevier

【 摘 要 】

A series of gamma-butyrolactone derivatives, including some spiranic ones, was obtained through de-symmetrization of the corresponding prochiral 3-substituted cyclobutanones via Baeyer-Villiger monooxygenase (BVMO)-catalyzed oxidation. After reaction optimization using several commercial enzymes, both antipodes of various lactones were synthesized in most cases with >90% conversion and >80% enantiomeric excess under mild reaction conditions. In some cases alcohol formation was also observed (up to 40% conversion) as an undesired side reaction due to the presence of alcohol dehydrogenases in these preparations. Selected transformations were achieved on a 100 mg scale showing the possibilities of these oxidative biocatalysts as a new source of highly interesting compounds. (C) 2015 Elsevier Ltd. All rights reserved.

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