title: Biocatalytic reduction of racemic 2-arenoxycycloalkanones by yeasts P. glucozyma and C. glabrata: one way of achieving chiral 2-arenoxycycloalcohols.
abstract: Chiral β-aryloxy alcohols are interesting building blocks that form part of drugs like β adrenergic antagonists. Acquiring cyclic rigid analogs to obtain more selective drugs is interesting. Thus, we used whole cells of yeast strains Pichia glucozyma and Candida glabrata to catalyze the reduction of several 2-arenoxycycloalkanones to produce chiral 2-arenoxycycloalcohols with good/excellent enantioselectivity. In both cases, the alcohol configuration that resulted from the carbonyl group reduction was S. Yeast P. glucozyma allowed the conversion of both enantiomers of the starting material to produce 2-arenoxycycloalcohols with configuration (1S, 2R) and (1S, 2S). The reaction with C. glabrata nearly always allowed the kinetic resolution of the starting ketone, recovering 2-arenoxycycloalkanone with configuration S and (1S, 2R)-2-arenoxycycloalcohol.All the four possible stereoisomers of 2-phenoxycyclohexanol and the two enantiomers of 2-phenoxycyclohexanone were obtained by combining the biocatalyzed reaction with the oxidation/reduction of the chiral compounds with standard reagents. This is a simple approach for the synthesis of the rigid chiral moiety 2-arenoxycycloalcohols contained in putative β-blockers 2-arenoxycycloalkanepropanolamines.
authors.affiliation: Departament de Química Orgànica, Facultat de Farmàcia, Universitat de València, Vicent Andrés Estellés s/n, E-46100 Burjassot, València, Spain. cecilia.andreu@uv.es.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Andreu
authors.affiliation: Departament de Química Orgànica, Facultat de Farmàcia, Universitat de València, Vicent Andrés Estellés s/n, E-46100 Burjassot, València, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Peña
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de València, Dr. Moliner 50, E-46100 Burjassot, València, Spain. m.del.olmo@uv.es.
authors.forename: Marcel Lí
authors.initials: ML
authors.lastname: Del Olmo
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000737:chemistry; D000438:Alcohols / Q000737:chemistry*; D055162:Biocatalysis; D041221:Candida glabrata / Q000378:metabolism*; D003511:Cyclohexanols / Q000737:chemistry*; D003512:Cyclohexanones / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D010084:Oxidation-Reduction; D010843:Pichia / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000319:Adrenergic beta-Antagonists; D000438:Alcohols; D003511:Cyclohexanols; D003512:Cyclohexanones; D007659:Ketones
keywords: Biocatalyst; C. glabrata; Chiral 2-arenoxycycloalcohols; Kinetic resolution; P. glucozyma