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Containing Nucleoside Coenzyme B <sub> 12 </ Sub> Analogue Study

Posted on:1994-02-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:H YanFull Text:PDF
GTID:1111360185466897Subject:Inorganic Chemistry
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Coenzyme B12(i.e. 5'-deoxyadenosylcobalamin) is one organometallic compound in vivo. It is now generally agreed that coenzyme B12 serves as the cofactor for some mutase-catalyzed substrate rearrangements and for nucleotide reductase-participated in reduction of nucleotides to deoxy nucleotides. For well understanding the actions of coenzyme B12 . a large number of protein-free models (excess 3000) have been synthesized, and their various properties have also been investigated. The coenzyme B12 analogues containing different ribose rings and bases have been reported, but had only a few examples and were lack of various studies. In my present work, 2',5'-dideoxynucleosidylcobalamins and 2',5'-dideoxy nucleosidylcobinamides were prepared and characterized, their thermodynamic and dynamic properties as well as mechanism under thermolysis were investigated. It is especially important for an understanding of the coenzyme's roles to determine Co-C bond dissociation energy and to study the factors that influence such bond dissociation energy.In this thesis, eleven ligands of 5'-O-p-tosyl-deoxynucleosides were synthesized, four of them were first reported, ie. 5-bromo-5'-O-p-tosyl-2'-deoxycytidine, 5'-O-p-tosyl-2',3'-didehydro-2',3'-dideoxy adenosine, 5'-O-p-tosyl-2',3'-didehydro-2',3'-dideoxyuridine, 5'-O-p -tosyl-2',3'-dideoxyuridine. All ligands were characterized by UV, 1HNMR and partly by EA, MS.Eleven complexes(cobalamin and cobinamide) were synthesized, six of them were first reported. These include 2'.5'-dideoxycytidylcobalamin, 2',5'-dideoxyuridinylcobalamin, 2',5'-dideoxycytidylcobinamide, 2',5'-dide oxyuridinylcobinamide, 2',5'-dideoxyadenosylcobinamide and 5'-deoxythy midylcobinamide.All of above complexes were characterized by UV-vis and 1HNMR. Their 1H chemical shifts were assigned by COSY, Relay-COSY, TOCSY and NOESY, and coupling constants (JH-h) were determined by J-Resolved spectra. For 5'-deoxyadenosylcobinamide, sixty-one of sixty-five non-exchangeable protons were assigned and compared with reported 1H assignments for the base-on and base-off forms of coenzyme B12 .2',5'-dideoxynucleosidyl radicals and B12. derived from anaerobic photolysis of 2',5'-dideoxynucleosidylcobalamin solutions were first identified by ESR spectroscopy. By using tNB as a radical trap, nitroxide radicals were obtained, ESR spectra of the adducts show 1:1:1:1 quartet due to the presence of chiral β-carbon atom. The origin of 1 2-line spectrum and the...
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