Preparation of chiral β-hydroxytriazoles in one-pot chemoenzymatic bioprocesses catalyzed by Rhodotorula mucilaginosa

摘要

Chemoenzymatic strategies for the preparation of enantiopure beta-hydroxytriazoles were designed. These and other related compounds are particularly relevant because of their antitubercular bioactivities and as beta-adrenergic receptor blockers. The ability of Rhodotorula mucilaginosa LSL to stereoselectively reduce prochiral ketones coupled to copper(I)-catalyzed azide-allcyne cycloaddition was exploited. The reactions were performed in aqueous medium and at room temperature. R. mucilaginosa LSL offered the advantage of internal redox cofactor recycling. Notably, the biocatalyst was compatible with all the chemicals required namely sodium azide, copper sulfate and alkynes and showed a broad substrate scope reducing small-bulky and bulky-bulky ketones stereo selectively. Considering this, two one-pot processes were assessed to synthesize enantiopure (R)-beta-hydroxytriazoles. A one-pot, three-step sequential transformation allowed obtaining enantiopure products up to 65% yield starting from alpha-chloro arylketones. On the other hand, with a-bromo arylketones, a one-pot cascade process furnished the same products in ca 80% isolated yield.