SYNTHETIC MODEL OF ACTIVE-SITE OF COENZYME B-12 DEPENDENT METHYLMALONYL-COA MUTASE

被引:57
作者
FLOHR, H [1 ]
PANNHORST, W [1 ]
RETEY, J [1 ]
机构
[1] UNIV KARLSRUHE, INST KRISTALLOG, D-7500 KARLSRUHE, FED REP GER
关键词
D O I
10.1002/hlca.19780610509
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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. Copyright © 1978 Verlag GmbH & Co. KGaA, Weinheim
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页码:1565 / 1587
页数:23
相关论文
共 78 条
[61]  
SCHAFFLER J, UNPUBLISHED
[62]  
Schrauzer G.N., 1976, ANGEW CHEM, V88, P465
[63]   REACTIONS OF COBALT(I) SUPERNUCLEOPHILES . ALKYLATION OF VITAMIN B12S COBALOXIMES(I) AND RELATED COMPOUNDS [J].
SCHRAUZER, GN ;
DEUTSCH, E .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1969, 91 (12) :3341-+
[64]   COENZYM B12-MODELLE [J].
SCHRAUZER, GN ;
KOHNLE, J .
CHEMISCHE BERICHTE-RECUEIL, 1964, 97 (11) :3056-&
[65]   PHOTOCHEMICAL AND THERMAL COBALT-CARBON BOND CLEAVAGE IN ALKYLCOBALAMINS AND RELATED ORGANOMETALLIC COMPOUNDS . A COMPARATIVE STUDY [J].
SCHRAUZER, GN ;
SIBERT, JW ;
WINDGASSEN, RJ .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1968, 90 (24) :6681-+
[66]   DIE SYNTHESE VON ACETYLEN-CARBONYL-VERBINDUNGEN DURCH FRAGMENTIERUNG VON ALPHA BETA-EPOXY-KETONEN MIT P-TOLUOLSULFONYLHYDRAZIN [J].
SCHREIBE.J ;
FELIX, D ;
ESCHENMO.A ;
WINTER, M ;
GAUTSCHI, F ;
SCHULTEE.KH ;
SUNDT, E ;
OHLOFF, G ;
KALVODA, J ;
KAUFMANN, H ;
WIELAND, P ;
ANNER, G .
HELVETICA CHIMICA ACTA, 1967, 50 (07) :2101-&
[67]   MECHANISM OF ACTION OF COENZYME B-12 - ROLE OF THIOESTER IN A NONENZYME MODEL REACTION FOR COENZYME B-12 DEPENDENT ISOMERIZATION OF METHYLMALONYL COENZYME-A TO SUCCINYL COENZYME-A [J].
SCOTT, AI ;
KANG, K .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1977, 99 (06) :1997-1999
[68]   HIGH TEMPERATURE REACTIONS OF IODINE WITH HYDROCARBONS .3. REARRANGEMENT OF ALIPHATIC FREE RADICALS [J].
SLAUGH, LH ;
RALEY, JH ;
MULLINEAUX, RD .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1963, 85 (20) :3180-&
[69]  
SPRECHER M, 1966, J BIOL CHEM, V241, P872
[70]  
SPRECHER M, 1966, J BIOL CHEM, V241, P864