ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
A synthetic model of the active site of the coenzyme B12 dependent methylmalonyl-CoA mutaseThe 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.
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19780610509
Permalink