Boron transition state analogue

The reaction is proposed to proceed from the anion (9) of A/-aminocatbonylaspattic acid [923-37-5] to dehydrooranate (11) via the tetrahedral activated complex (10), which is a highly charged, unstable sp carbon species. In order to design a stable transition-state analogue, the carboxylic acid in dihydrooronate (hexahydro-2,6-dioxo-4-pyrimidinecarboxylic acid) [6202-10-4] was substituted with boronic acid the result is a competitive inhibitor of dibydroorotase witb a iC value of 5 ]lM. Its inhibitory function is supposedly due to tbe formation of tbe charged, but stable, tetrabedral transition-state intermediate (8) at tbe active site of tbe enzyme. 

A very interesting tautomeric system is presented by the civ-fused tetrahydro[l,3,2]dioxaborino [5,4-cf]-l,3,2-dioxaborin (122). This is prepared from a threitol type precursor and is obtained as a mixture with isomer (123) in a ratio of 3 1 (Equation (2)). The particular stereochemistry of (122) permits the molecule to adopt a conformation in which the two boron atoms and two of the oxygen atoms assume a four-centered transition state (124), thus allowing establishment of a dynamic equilibrium with the isomeric structure (123) (Scheme 3). The trans-fused analogue of (122), prepared from an erythritol type precursor, is unable to enter into this tautomeric equilibrium (80LAH76). 

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