title: Synthesis, protonation behavior, conformational analysis, and regioselective enzymatic acylation of the novel diamino analogue of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU).
abstract: (E)-3',5'-Diamino-5-(2-bromovinyl)-2',3',5'-trideoxyuridine (5), the diamino analogue of BVDU (1), was synthesized from BVDU. The protonation behavior of 5 has been studied by means of pH-metric measurements and NMR spectroscopy. This study allows the determination of the basicity constants and the stepwise protonation sites. Thus, the main species at physiological pH is the monoprotonated form. The conformational analysis of this nucleoside analogue was also carried out through 1H NMR spectroscopy. In addition, a convenient synthesis of N-3' and N-5' acylated derivatives was developed by regioselective enzymatic acylation. Thus, Candida antarctica lipase B (CAL-B) selectively acylated the 5'-amino group, thus furnishing nucleosides 8. On the other hand, immobilized Pseudomonas cepacia lipase (PSL-C) exhibited the opposite selectivity, conferring acylation at the 3'-amino group, thus affording derivatives 9.
authors: Departamento de Química Orgánica e Inorgánica, Facultad de Química, Universidad de Oviedo, Oviedo, Spain.
authors: Iván
authors: I
authors: Lavandera
authors: Susana
authors: S
authors: Fernández
authors: Miguel
authors: M
authors: Ferrero
authors: Erik
authors: E
authors: De Clercq
authors: Vicente
authors: V
authors: Gotor
mesh_terms: D000215:Acylation; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D016956:Burkholderia cepacia / Q000201:enzymology; D002175:Candida / Q000201:enzymology; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011522:Protons
chemical_list: D011522:Protons; C020235:brivudine; D008049:Lipase; D001973:Bromodeoxyuridine