Stereochemical aspects of cytosolic epoxide hydrolase hydration of methyl diepoxystearates

Abstract

Hydration of methyl diepoxystearate ( 2) at high cytosolic epoxide hydrolase (CEH) concentration produces the corresponding tetraol, while at physiological CEH concentration four tetrahydrofuran diol products ( 3–6) are produced. These same four products are obtained in the acid-catalyzed hydration of 2. Spectroscopic studies, primarily EI mass spectrometry and difference spectrum NOE, are reported which establish the regio- and stereoselectivity of 2 → 3–6 (MS differentiating 3 4 from 5 6 and NOE differentiating 3 5 from 4 6 ). The observed syn arrangement of the two adjacent groups (i.e., substituents at C 2 and C 3) in the four THF-diols can only arise from an A 2 type opening of the first epoxide. The resulting epoxydiol intermediate then cyclizes by A 2 opening of the second cis-epoxide as established by synthesis of these hypothetical epoxydiol intermediates and their subsequent conversion to THF-diols 3–6.