FACILE ALPHA/BETA-DIASTEREOMERISM IN ORGANOCOBALT CORRINS - EVIDENCE FOR THERMODYNAMIC CONTROL IN THE SYNTHESIS OF ALKYLCOBAMIDES

被引:16
作者
BROWN, KL
ZOU, X
机构
[1] Department of Chemistry, Mississippi State University, Mississippi State, Mississippi 39762, Box CH
关键词
D O I
10.1021/ic00022a019
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
Reductive alkylation of aquacobalamin with certain alkyl halides is known to produce a mixture of diastereomeric beta-alkylcobalamins (with the organic ligand in the "upper" axial ligand position) and alpha-alkylcobalamins (with the organic ligand in the "lower" axial ligand position) when the reducing agent is zinc/acetic acid. However, reduction with sodium borohydride followed by alkylation produces only beta-alkylcobalamins. This difference has now been shown to be a pH effect, and the pH dependence of the relative proportions of alpha- and beta-diastereomers produced upon reductive alkylation of aquacobalamin with CF3CH2I, CF3I, and NCCH2Br has been studied. In each case, the fraction of the alkylcobalamin as the alpha-diastereomer increases with increasing acidity, following a typical titration curve. The apparent pK(a)'s obtained from these data (3.04 +/- 0.03, 2.69 +/- 0.02, and 2.25 +/- 0.02 for R = CF3CH2, CF3, and NCCH2, respectively) are shown to be consistent with the hypothesis that the products are under equilibrium control and that the pH dependence is due to the base-on/base-off equilibrium of the product beta-alkylcobalamin. The alternative of kinetically controlled products requires that the species being alkylated in zinc/acid reducing systems is cob(II)alamin, since cob(I)alamin is base-off at all pH's. The pK(a) for the base-on/base-off reaction of cob(II)alamin has been determined spectrophotometrically to be 3.10 +/- 0.01. However, interpretation of the apparent pK(a)'s for the pH dependence of the diastereomeric outcome of the reductive alkylation of aquacobalamin assuming kinetic control leads to relative reactivities of the base-off and base-on species of cob(II)alamin which are not consistent with the observed rates of product formation or with literature data on the reaction of cob(II)alamin with alkyl halides. Studies of the temperature dependence of the diastereomer ratio in the analogous alkylcobinamides show that the apparent equilbrium between diastereomers is entropically controlled.
引用
收藏
页码:4185 / 4191
页数:7
相关论文
共 40 条
[1]   REACTIONS OF COBALT(II) MACROCYCLES WITH ALKYL AND ALKYLPEROXY RADICALS [J].
BAKAC, A ;
ESPENSON, JH .
INORGANIC CHEMISTRY, 1989, 28 (24) :4319-4322
[2]  
BARKER HA, 1960, J BIOL CHEM, V235, P480
[3]   REDUCTION OF VITAMIN-B12 [J].
BEAVEN, GH ;
JOHNSON, EA .
NATURE, 1955, 176 (4496) :1264-1265
[4]   REACTIONS OF VITAMIN-B12R WITH ORGANIC HALIDES [J].
BLASER, HU ;
HALPERN, J .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1980, 102 (05) :1684-1689
[5]   HETERONUCLEAR NMR-STUDIES OF COBALAMINS .4. ALPHA-RIBAZOLE-3'-PHOSPHATE AND THE NUCLEOTIDE LOOP OF BASE-ON COBALAMINS [J].
BROWN, KL ;
HAKIMI, JM .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1986, 108 (03) :496-503
[6]   ACID-BASE PROPERTIES OF ALPHA-RIBAZOLE AND THE THERMODYNAMICS OF DIMETHYLBENZIMIDAZOLE ASSOCIATION IN ALKYLCOBALAMINS [J].
BROWN, KL ;
HAKIMI, JM ;
NUSS, DM ;
MONTEJANO, YD ;
JACOBSEN, DW .
INORGANIC CHEMISTRY, 1984, 23 (10) :1463-1471
[8]   EFFECTS OF AXIAL LIGATION ON THE THERMOLYSIS OF BENZYLCOBAMIDES AND NEOPENTYLCOBAMIDES - ANALYSIS OF THE BASE-ON EFFECT [J].
BROWN, KL ;
BROOKS, HB .
INORGANIC CHEMISTRY, 1991, 30 (18) :3420-3430
[9]   HETERONUCLEAR NMR-STUDIES OF COBALAMINS .12. FURTHER-STUDIES OF DICYANOCOBAMIDES AND THE COMPLETE PROTON, CARBON, AND AMIDE NITROGEN NMR ASSIGNMENTS OF DICYANOCOBALAMIN [J].
BROWN, KL ;
BROOKS, HB ;
GUPTA, BD ;
VICTOR, M ;
MARQUES, HM ;
SCOOBY, DC ;
GOUX, WJ ;
TIMKOVICH, R .
INORGANIC CHEMISTRY, 1991, 30 (18) :3430-3438
[10]   FACILE ALPHA-BETA DIASTEREOMERISM IN (2,2,2-TRIFLUOROETHYL)COBALT CORRINS [J].
BROWN, KL ;
EVANS, DR .
INORGANIC CHEMISTRY, 1990, 29 (14) :2559-2561