Examination of spacer effects on stereochemical recognition of a remote sterically hindered chiral center in lipase-catalyzed acylation

Abstract

Abstract To date, the enzyme-catalyzed kinetic resolution of the secondary alcohol [Ar-C*H(CH 3 )OH, Ar = 2′,4′,6′-triisopropylphenyl] has not been available, due to high steric hindrance around the hydroxy group. To achieve resolution, the reaction site was extended by the introduction of two kinds of spacers, [ C( O)CH 2 ] and [ C( O)C**HCN ]. In the first substrate, the recognition of remote chirality [Ar C*H(CH 3 )O C( O)CH 2 OH] by acylation with Burkholderia cepacia lipase was examined by changing reaction conditions and acyl donors. An E = 22 in the preference of (1′ R )-isomer, was recorded with vinyl acetate as an acyl donor at 25 °C. In the second substrate, there was a matched enantiomeric pair [stereoselective ratio at C-1′ = 15, in the preference of (1′ R )-isomer] and a mismatched pair [stereoselective ratio at C-1′ = 2.5, in the preference of (1′ S )-isomer] based on the relative stereochemistry between the two chiral centers [Ar C*H(CH 3 )O C( O)C**HCN OH].