96026-63-0Relevant academic research and scientific papers
Enzymatic parallel kinetic resolution of mixtures of d / l 2′-deoxy and ribonucleosides: An approach for the isolation of β- L -nucleosides
Martinez-Montero, Saul,Fernandez, Susana,Sanghvi, Yogesh S.,Gotor, Vicente,Ferrero, Miguel
experimental part, p. 6605 - 6613 (2010/11/17)
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 PSLs 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.
