Beschreibung:
<jats:p><jats:bold>A synthetic model of the active site of the coenzyme B<jats:sub>12</jats:sub> dependent methylmalonyl‐CoA mutase</jats:bold></jats:p><jats:p>The synthesis of a bridged cobaloxime with a built‐in methylmalonic ester moiety is described. 2‐Brommethyl‐2‐methylmalonic acid dichloride (<jats:bold>5</jats:bold>) afforded upon reaction with 5‐heptin‐1‐ol (<jats:bold>4</jats:bold>) the corresponding diester <jats:bold>6</jats:bold>. Subsequent treatment of <jats:bold>6</jats:bold> 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 (<jats:bold>8</jats:bold>). Reaction of <jats:bold>8</jats:bold> with cobalt (II) chloride, pyridine and sodium borohydride furnished in 7% yield the bridged cobaloxime <jats:bold>10</jats:bold>, which was spectroscopically characterized. Short term irradiation of <jats:bold>10</jats:bold> in methanol caused the exchange of the axial pyridine ligand by a solvent molecule affording <jats:bold>10a</jats:bold>, the structure of which has been determined by X‐ray crystallography. Long term irradiation of <jats:bold>10</jats:bold> 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‐B<jats:sub>12</jats:sub> catalysed rearrangement of methylmalonyl‐CoA are discussed.</jats:p>