Enzymatic parallel kinetic resolution of mixtures of D/L 2'-deoxy and ribonucleosides: an approach for the isolation of β-L-nucleosides.
We have developed a lipase-catalyzed parallel kinetic resolution of mixtures of β-D/L-nucleosides. The opposite selectivity during acylation exhibited by Pseudomonas cepacia lipase (PSL-C) with β-D- and β-L-nucleosides furnished acylated compounds that have different R(f) values. As a consequence, isolation of both products was achieved by simple column chromatography. Computer modeling of the transition-state analogues during acylation of β-D- and β-L-2'-deoxycytidine with PSL-C was carried out to explain the high selectivity. PSL-C favored the 3'-O-levulination of the β-D enantiomer, whereas the 5'-OH group was acylated in 2'-deoxy-β-L-cytidine. In both cases, the cytosine base was placed in the alternate hydrophobic pocket of PSL's substrate-binding site, where it can form extra hydrogen bonds (in addition to the five essential catalytically relevant hydrogen bonds) that stabilize these intermediates catalyzing the selective acylation of β-D/L-nucleosides.
Martínez-Montero
Saúl
S
Departamento de Química Orgánica e Inorgánica and Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, 33006-Oviedo (Asturias), Spain.
Fernández
Susana
S
Sanghvi
Yogesh S
YS
Gotor
Vicente
V
Ferrero
Miguel
M
D055162:Biocatalysis; D016956:Burkholderia cepacia / Q000201:enzymology*; D007700:Kinetics; D008049:Lipase / Q000737:chemistry / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000737:chemistry* / Q000302:isolation & purification; D013237:Stereoisomerism
D009705:Nucleosides; D008049:Lipase