Synthesis of a Deoxo Analog of (3 S )‐Citryl‐CoA: (3 R )‐3,4‐Dicarboxy‐3‐hydroxybutyl‐CoA

The citryl thioester 1 was reduced in mmol scale with sodium tetrahydroborate to yield 2‐hydroxy‐2‐(2‐hydroxyethyl)butanedioic acid ( 2 ) in 70% yield. The acid was converted into the dimethyl ester 3 and further to the 2‐(2‐bromoethyl) derivative 4 . This bromide was used to prepare the title compound 7 by reaction with coenzyme A, either directly, or by hydrolysis of the isolated dimethyl ester 6 . The kinetic and X‐ray crystallographic results obtained with 7 and the enzyme citrate synthase of the tricarboxylic acid cycle are discussed.