Ein synthetisches Modell für die Aktivstelle der Coenzym‐B12‐abhängigen Methylmalonyl‐CoA‐Mutase

A synthetic model of the active site of the coenzyme B12 dependent methylmalonyl‐CoA mutase The synthesis of a bridged cobaloxime with a built‐in methylmalonic ester moiety is described. 2‐Brommethyl‐2‐methylmalonic acid dichloride (5) afforded upon reaction with 5‐heptin‐1‐ol (4) the corresponding diester 6. Subsequent treatment of 6 with ozone, dimethylsulfide and hydroxylamine hydrochloride led to the pentadentate ligand: 10‐brommethyl‐10‐methyl‐9, 11‐dioxo‐8, 12‐dioxa‐nonadecane‐2, 3, 17, 18‐tetraone tetraoxime (8). Reaction of 8 with cobalt (II) chloride, pyridine and sodium borohydride furnished in 7% yield the bridged cobaloxime 10, which was spectroscopically characterized. Short term irradiation of 10 in methanol caused the exchange of the axial pyridine ligand by a solvent molecule affording 10a, the structure of which has been determined by X‐ray crystallography. Long term irradiation of 10 in methanol or ethanol led to irreversible cleavage of the Co, C‐bond. Upon alkaline hydrolysis the degradation product afforded methylsuccinic acid in 82–95% yield. No incorporation of solvent protons into this product could be observed. Implications of these findings for the mechanism of the coenzyme‐B12 catalysed rearrangement of methylmalonyl‐CoA are discussed.