5-[4-(1-Hydroxyethyl)phenyl]-10,15,20-triphenylporphyrin as a Probe of the Transition-State Conformation in Hydrolase-Catalyzed Enantioselective Transesterifications Tadashi Ema Masahito Jittani Kenji Furuie Masanori Utaka Takashi Sakai 10.1021/jo0109063.s001 https://acs.figshare.com/articles/journal_contribution/5-_4-_1-Hydroxyethyl_phenyl_-10_15_20-triphenylporphyrin_as_a_Probe_of_the_Transition-State_Conformation_in_Hydrolase-Catalyzed_Enantioselective_Transesterifications/3690576 5-[4-(1-Hydroxyethyl)phenyl]-10,15,20-triphenylporphyrin (<b>1a</b>) and zinc porphyrin <b>1b</b> were designed and synthesized to experimentally examine the validity of the transition-state model previously proposed for the lipase-catalyzed kinetic resolution of secondary alcohols. The lipases from <i>Pseudomonas cepacia</i> (lipase PS), <i>Candida antarctica</i> (CHIRAZYME L-2), <i>Rhizomucor miehei</i> (CHIRAZYME L-9), and <i>Pseudomonas aeruginosa</i> (lipase LIP) exhibited excellent enantioselectivity (<i>E</i> >100 at 30 °C). Subtilisin Carlsberg from <i>Bacillus licheniformis</i> (ChiroCLEC-BL) also showed high enantioselectivity for <b>1a</b> (<i>E</i> = 140 at 30 °C), and the thermodynamic parameters were determined: ΔΔ<i>H</i><sup>⧧</sup> = −6.8 ± 0.8 kcal mol<sup>-1</sup>, ΔΔ<i>S</i><sup>⧧</sup> = −13 ± 3 cal mol<sup>-1</sup> K<sup>-1</sup>. Lipases and subtilisin showed <i>R</i>- and <i>S</i>-preference for <b>1</b>, respectively. The mechanisms underlying the experimental observations are explained in terms of the transition-state models. The large secondary alcohol <b>1</b> is a powerful tool for investigating the conformation of the transition state of the enzyme-catalyzed reactions. The fact that <b>1</b> was resolved with high enantioselectivity strongly suggests that the <i>gauche</i> conformation, but not the <i>anti</i> conformation, is taken in the transition state, in agreement with the transition-state models involving the stereoelectronic effect. 2002-03-01 00:00:00 enantioselectivity zinc porphyrin 1 b ΔΔ mol CHIRAZYME transition state PS Pseudomonas conformation lipase Hydroxyethyl model