Isomerism in Organocobalt Derivatives of Vitamin B12

该奖项由无机化学、生物无机化学和有机金属化学计划颁发，涉及生物无机化学领域。该项目涉及维生素B-12衍生物的合成和反应化学。这种维生素的各种衍生物作为辅酶在从细菌到人类的各种有机体中催化大约15个酶反应。最近发现的维生素B-12的有机钴衍生物中的两种异构体的细节将被研究。第一个涉及当钴酰胺(缺乏侧链轴向配体的维生素B-12衍生物)与一些但不是其他烷基化试剂还原烷基化时，形成上(β)和下(α)烷基钴衍生物。研究了不同烷基化试剂反应结果不同的原因，以及两种异构体的形成机理和异构体相互转化的条件。初步结果表明，这些异构体的相互转化可能涉及新的二烷基钴酰胺物种。第二种类型的异构化包括当水钴胺与烷氧基乙基溴化物还原烷基化时，形成一对明显的异构烷基钴衍生物。它们不可能是α和β异构体，但被认为是2-烷氧基乙基和1-烷氧基乙基钴胺。用同位素富集型烷氧基乙基溴化物合成的产物的核磁共振波谱将确定其结构，并将研究这些异构体对的形成机理。还将确定异构体相互转化的条件。

This award from the Inorganic, Bioinorganic and Organometallic Chemistry Program is in the area of bioinorganic chemistry. The project deals with the synthesis and reaction chemistry of derivatives of vitamin B-12. Various derivatives of this vitamin serve as coenzymes in the catalysis of about 15 enzymic reactions in organisms ranging from bacteria to human beings. Details of two kinds of recently discovered isomerism in organocobalt derivatives of vitamin B-12 will be studied. The first involves formation of upper (beta) and lower (alpha) alkylcobalt derivatives when cobinamides (vitamin B-12 derivatives lacking the pendant axial ligand) are reductively alkylated with some, but not other alkylating agents. The reason for the different outcomes with different alkylating agents will be studied as well as the mechanism of formation of two isomers and the conditions under which the isomers can be interconverted. Preliminary results indicate that interconversion of such isomers may involve novel dialkylcobinamide species. The second type of isomerism involves formation of pairs of apparently isomeric alkylcobalt derivatives when aquocobalamin is reductively alkylated with alkoxyethyl bromides. These cannot be alpha and beta isomers, but are believed to be 2-alkoxyethyl and 1-alkoxyethyl cobalamins. The structures will be determined by NMR spectroscopy of products synthesized with isotopically enriched alkoxyethyl bromides, and the mechanism of formation of such pairs of isomers will be studied. The conditions under which the isomers are interconverted will be determined also.