Chemoenzymatic synthesis of calcilytic agent NPS-2143 employing a lipase-mediated resolution protocol

The kinetic resolution of chlorohydrin (+/-)-6 has been successfully carried out via a lipase-mediated transesterification with vinyl acetate in organic as well as ionic liquid media to yield (R)-alcohol 6 and (S)-acetate 7 in high enantioselectivity. An enantioconvergent synthesis has also been achieved by a Mitsunobu esterification of a mixture of (R)-alcohol 6 and (S)-acetate 7 in one pot to convert the (R)-alcohol 6 to (S)-acetate 7. (S)-Acetate 7 has been hydrolyzed by LiOH center dot H2O to give epoxide (R)-2. This enantiopure epoxide has been used as a chiral precursor for the synthesis of calcilytic agent NPS-2143. (c) 2005 Elsevier Ltd. All rights reserved.