TY - JOUR
T1 - Substrate modification to increase the enantioselectivity of hydrolases. A route to optically-active cyclic allylic alcohols.
AU - Gupta, Ajay K.
AU - Kazlauskas, Romas J.
PY - 1993/5
Y1 - 1993/5
N2 -
The esterase-catalyzed resolution of the cyclic allylic acetates-1-acetyloxy-2-cyclopentene, 1-acetyloxy-2-cyclohexene, and 1-acetyloxy-2-cycloheptene - was not enantioseleclive. We hypothesized that this inefficiency stems from the similarity in size of the substituents at the stereocenter (CH
2
CH
2
vs. CHCH). To increase the enantioselectivity, we resolved precursors to these cyclic allylic alcohols: esters of trans-2-bromocycloalkanols (C
5
, C
6
, C
7
). These esters had a larger difference in the size of the substituents (CH
2
vs. CHBr) at the stereocenter and were efficiently resolved by both cholesterol esterase and lipase from Pseudomonas cepacia (Amano P, PCL). A synthetic-scale resolution with PCL yielded the (1S,2S)-1-butanoyloxy-2-bromocycloalkanes in >98% ee. Heating with DBU to eliminate HBr, followed by reduction with LiAlH
4
to cleave the ester, yielded the allylic alcohols: (S)-(-)-2-cyclopenten-1-ol (65% ee), (S)-(-)-2-cyclohexen-1-ol (>99% ee), and (S)-(-)-2-cyclohepten-1-ol (>98% ee).
AB -
The esterase-catalyzed resolution of the cyclic allylic acetates-1-acetyloxy-2-cyclopentene, 1-acetyloxy-2-cyclohexene, and 1-acetyloxy-2-cycloheptene - was not enantioseleclive. We hypothesized that this inefficiency stems from the similarity in size of the substituents at the stereocenter (CH
2
CH
2
vs. CHCH). To increase the enantioselectivity, we resolved precursors to these cyclic allylic alcohols: esters of trans-2-bromocycloalkanols (C
5
, C
6
, C
7
). These esters had a larger difference in the size of the substituents (CH
2
vs. CHBr) at the stereocenter and were efficiently resolved by both cholesterol esterase and lipase from Pseudomonas cepacia (Amano P, PCL). A synthetic-scale resolution with PCL yielded the (1S,2S)-1-butanoyloxy-2-bromocycloalkanes in >98% ee. Heating with DBU to eliminate HBr, followed by reduction with LiAlH
4
to cleave the ester, yielded the allylic alcohols: (S)-(-)-2-cyclopenten-1-ol (65% ee), (S)-(-)-2-cyclohexen-1-ol (>99% ee), and (S)-(-)-2-cyclohepten-1-ol (>98% ee).
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U2 - 10.1016/S0957-4166(00)80126-3
DO - 10.1016/S0957-4166(00)80126-3
M3 - Article
AN - SCOPUS:0027196612
SN - 0957-4166
VL - 4
SP - 879
EP - 888
JO - Tetrahedron: Asymmetry
JF - Tetrahedron: Asymmetry
IS - 5
ER -