Synthesis of Enantiomerically Pure 1,5,5‐Trideuterated cis‐ and trans‐2,4‐Dioxa‐3‐phosphadecalins. 31P‐NMR Evidence of Covalent‐Bond Formation and the Stereochemical Implications in the Course of the Inhibition of δ‐Chymotrypsin

Abstract

AbstractThe irreversible inhibition of δ‐chymotrypsin with the enantiomerically pure, P(3)‐axially and P(3)‐equatorially X‐substituted cis‐ and trans‐configurated 2,4‐dioxa‐3‐phospha(1,5,5‐2H3)bicyclo[4.4.0]decane 3‐oxides (X=F, 2,4‐dinitrophenoxy) was monitored by 31P‐NMR spectroscopy. 1H‐Correlated 31P{2H}‐NMR spectra enabled the direct observation of the vicinal coupling (3J) between the P‐atom of the inhibitor and the CH2O moiety of Ser195 (=‘Ser195’(CH2O)), thus establishing the covalent nature of the ‘Ser195’(CH2OP) bond in the inhibited enzyme. The stereochemical course of the phosphorylation is dependent on the structure of the inhibitor, and neat inversion, both inversion and retention, as well as neat retention of the configuration at the P‐atom was found.