Inhibition of insect juvenile hormone epoxide hydrolase: asymmetric synthesis and assay of glycidol-ester and epoxy-ester inhibitors of trichoplusia ni epoxide hydrolase.

Abstract:

:Juvenile hormone (JH) undergoes metabolic degradation by two major pathways involving JH esterase and JH epoxide hydrolase (EH). While considerable effort has been focussed on the study of JH esterase and the development of inhibitors for this enzyme, much less has been reported on the study of JH-EH. In this work, the asymmetric synthesis of two classes of inhibitors of recombinant JH-EH from Trichoplusia ni, a glycidol-ester series and an epoxy-ester series is reported. The most effective glycidol-ester inhibitor, compound 1, exhibited an I(50) of 1.2x10(-8) M, and the most effective epoxy-ester inhibitor, compound 11, exhibited an I(50) of 9.4x10(-8) M. The potency of the inhibitors was found to be dependent on the absolute configuration of the epoxide. In both series of inhibitors, the C-10 R-configuration was found to be significantly more potent that the corresponding C-10 S-configuration. A mechanism for epoxide hydration catalyzed by insect EH is also presented.

authors

Linderman RJ,Roe RM,Harris SV,Thompson DM

doi

10.1016/s0965-1748(00)00048-5

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

767-74

issue

8-9

eissn

0965-1748

issn

1879-0240

pii

S0965-1748(00)00048-5

journal_volume

30

pub_type

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