Stereoselective bioreduction of bulky-bulky ketones by the wild yeast Rhodotorula sp. LSL

AGUIRRE-PRANZONI C; BISOGNO FR; ORDEN AA; KURINA SANZ MB

Buzios

Simposio; VII Workshop on Biocatalysis and Biotransformation. 1Simposio Latinoamericano de Biocatálisis y Biotransformaciones; 2014

Universidade Federal do Rio de Janeiro

INTRODUCTION Although prochiral ketone bioreductions are widely used to generate optically pure sec-alcohols, stereoselective reduction towards bulky aromatic substrates are still rare. Most of the selective ADHs possessing a broad substrate spectrum resembles small bulky ketones, thus, the small substituent is limited to a sterically non demanding group such as methyl, ethyl, or chloromethyl [1]. Only a few organisms or enzymes have been reported for the reduction of bulky-bulky ketones [2, 3]. Rhodotorula sp. LSL is a chemo extremophile wild microorganism isolated from a landfarming. We have already showed its ability for the stereoselective reduction of a series of non-sterically demanding ketones, and its use as a lyophilized catalyst in one pot chemoenzymatic procedures was optimized [4]. Since to generate stereogenic centers in the last steps of the synthesis of pharmaceutically potential products is an ongoing hot topic, we choose beta-ketotriazoles as substrates to identify the abilities of this new catalyst of reducing bulky-bulky ketones. RESULTS AND DISCUSSION The beta-ketotriazoles were efficiently prepared by cycloaddition of beta-azidoketones with acetylenes catalyzed by Cu(I) in situ generated by the well known Huisgen reaction [5]. Both lyophilized and resting cells of Rhodotorula sp. LSL in buffer phosphate (pH 6.5) were successful to reduce in a stereoselective fashion 1mM of the substrates in 24 h of bioreaction. Conversions of the beta-ketotriazoles to the corresponding alcohols were complete and the stereoselectivity was excellent yielding the corresponding R enantiomers of the beta-hydroxitriazoles in agreement with the Prelog´s rule. These bioactive derivatives were already obtained by Ankati et al., but starting from the enantiopure antipodes of the 2-azido-1-arylethanols [6]. At the best of our knowledge, the preparation of enantioenriched alfa-hydroxitriazoles by stereoselective bioreduction of beta-ketotriazoles (scheme 1) was not reported until now. CONCLUSION The new wild biocatalyst Rhodotorula sp. LSL has the ability of reducing bulky-bulky ketones with excellent stereoselectivity. This facility was successfully used for the preparation of potentially bioactive enantiopure beta-hydroxitriazole derivatives. ACKNOWLEDGEMENTS UNSL (PROICO 2-1412); CONICET (PIP 2012-360) y ANPCyT (PICT 2011-1416)