title: O-Aryl α,β-d-ribofuranosides: synthesis & highly efficient biocatalytic separation of anomers and evaluation of their Src kinase inhibitory activity.
abstract: A series of peracetylated O-aryl α,β-d-ribofuranosides have been synthesized and an efficient biocatalytic methodology has been developed for the separation of their anomers which was otherwise almost impossible by column chromatographic or other techniques. The incubation of 2,3,5-tri-O-acetyl-1-O-aryl-α,β-d-ribofuranoside with Lipozyme® TL IM immobilized on silica led to the selective deacetylation of only one acetoxy group, viz the C-5'-O-acetoxy group of the α-anomer over the other acetoxy groups derived from the two secondary hydroxyl groups present in the molecule and also over three acetoxy groups (derived from one primary and two secondary hydroxyls of the β-anomer). This methodology led to the easy synthesis of both, α- and β-anomers of O-aryl d-ribofuranosides. All the arylribofuranosides were screened for inhibition of Src kinase. 1-O-(3-Methoxyphenyl)-β-d-ribofuranoside exhibited the highest activity for inhibition of Src kinase (IC(50)=95.0μM).
authors.affiliation: Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi, India.
authors.forename: Raman K
authors.initials: RK
authors.lastname: Sharma
authors.forename: Sukhdev
authors.initials: S
authors.lastname: Singh
authors.forename: Rakesh
authors.initials: R
authors.lastname: Tiwari
authors.forename: Deendayal
authors.initials: D
authors.lastname: Mandal
authors.forename: Carl E
authors.initials: CE
authors.lastname: Olsen
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.forename: Keykavous
authors.initials: K
authors.lastname: Parang
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Prasad
mesh_terms: D000107:Acetylation; D001203:Ascomycota / Q000201:enzymology; D002175:Candida / Q000201:enzymology; D004800:Enzymes, Immobilized / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008049:Lipase / Q000378:metabolism; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012266:Ribose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D013237:Stereoisomerism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004800:Enzymes, Immobilized; D047428:Protein Kinase Inhibitors; D012266:Ribose; D019061:src-Family Kinases; D008049:Lipase