title: The synthesis and characterization of 8-methoxy-5'-deoxyadenosylcobalamin: a coenzyme B(12) analog which, following Co-C bond homolysis, avoids cyclization of the 8-methoxy-5'-deoxyadenosyl radical.
abstract: The compound 8-methoxy-5'-deoxyadenosylcobalamin (8-MeOAdoCbl), has been synthesized in 37% yield and > or = 95% purity by HPLC, monitored at both 254 and 525 nm, or 90+/-2% purity as judged by the (1)H NMR spectrum of the aromatic cobalamin region. This is the first synthesis of this complex in which sufficient details are reported, where a yield and purity are reported, and where key problems in the synthesis and purification are overcome, so that 8-MeOAdoCbl can actually be obtained for use in other studies. Also demonstrated is the clean Co-C bond homolysis of 8-MeOAdoCbl to give initially 8-MeOAdoCbl and Co(II)Cbl in a UV-visible thermolysis experiment at 110 degrees C, results which show that the 8-MeO moiety suppresses the cyclization to the 8,5'-anhydro-adenosine otherwise seen for the adenosyl radical (Ado)*. Suppression of this cyclization pathway makes 8-MeOAdoCbl invaluable for studying the kinetic isotope effect (KIE) of the Ado* plus substrate H* abstraction reaction, a component of the first definitive test of Klinman's hypothesis that the optimization of enzyme catalysis may entail strategies that increase the probability of tunneling and thereby accelerate H* atom abstraction reaction rates.
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Doll
authors.forename: Paul E
authors.initials: PE
authors.lastname: Fleming
authors.forename: Richard G
authors.initials: RG
authors.lastname: Finke
mesh_terms: D003038:Cobamides / Q000138:chemical synthesis* / Q000737:chemistry; D005609:Free Radicals; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D014805:Vitamin B 12 / Q000031:analogs & derivatives*
chemical_list: C465816:8-methoxy-5'-deoxyadenosylcobalamin; D003038:Cobamides; D005609:Free Radicals; D014805:Vitamin B 12