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