Stereodivergent preparation of valuable γ- Or δ-hydroxy esters and lactones through one-pot cascade or tandem chemoenzymatic protocols

Article abstract of DOI:10.1021/cs4010024

A series of enantiopure hydroxy esters and lactones has been synthesized in a chemodivergent manner via alcohol dehydrogenase (ADH) reduction of the corresponding keto esters by means of cascade or tandem protocols. Thus, ADH from Rhodococcus ruber (ADH-A) or Lactobacillus brevis (LBADH) afforded both antipodes in a very selective way when dealing with small derivatives. With bulkier substrates, ADH from Ralstonia sp. (RasADH) was successfully employed to achieve the synthesis of enantioenriched γ- or δ-hydroxy esters. To isolate the corresponding lactones, two different approaches were followed: a cascade reaction by spontaneous cyclization of the hydroxy ester intermediate, or a one-pot two-step tandem protocol. Moreover, a chemoenzymatic route was designed to obtain a chiral brominated lactone, which enabled further modifications in a sequential fashion by Pd-catalyzed reactions, affording relevant functionalized lactones.