jo0109063_si_001.pdf (325.02 kB)
5-[4-(1-Hydroxyethyl)phenyl]-10,15,20-triphenylporphyrin as a Probe of the Transition-State Conformation in Hydrolase-Catalyzed Enantioselective Transesterifications
journal contribution
posted on 2002-03-01, 00:00 authored by Tadashi Ema, Masahito Jittani, Kenji Furuie, Masanori Utaka, Takashi Sakai5-[4-(1-Hydroxyethyl)phenyl]-10,15,20-triphenylporphyrin (1a) and zinc porphyrin 1b 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
Pseudomonas cepacia (lipase PS), Candida antarctica (CHIRAZYME L-2), Rhizomucor miehei
(CHIRAZYME L-9), and Pseudomonas aeruginosa (lipase LIP) exhibited excellent enantioselectivity
(E >100 at 30 °C). Subtilisin Carlsberg from Bacillus licheniformis (ChiroCLEC-BL) also showed
high enantioselectivity for 1a (E = 140 at 30 °C), and the thermodynamic parameters were
determined: ΔΔH⧧ = −6.8 ± 0.8 kcal mol-1, ΔΔS⧧ = −13 ± 3 cal mol-1 K-1. Lipases and subtilisin
showed R- and S-preference for 1, respectively. The mechanisms underlying the experimental
observations are explained in terms of the transition-state models. The large secondary alcohol 1
is a powerful tool for investigating the conformation of the transition state of the enzyme-catalyzed
reactions. The fact that 1 was resolved with high enantioselectivity strongly suggests that the gauche
conformation, but not the anti conformation, is taken in the transition state, in agreement with
the transition-state models involving the stereoelectronic effect.