O-Aryl α,β-d-ribofuranosides: Synthesis & highly efficient biocatalytic separation of anomers and evaluation of their Src kinase inhibitory activity

Raman K. Sharma, Sukhdev Singh, Rakesh Tiwari, Deendayal Mandal, Carl E. Olsen, Virinder S. Parmar, Keykavous Parang, Ashok K. Prasad

Research output: Contribution to journalArticle

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 (IC50 = 95.0 μM).

Original languageEnglish (US)
Pages (from-to)6821-6830
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number23
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

Fingerprint

src-Family Kinases
Hydroxyl Radical
Silicon Dioxide
Inhibitory Concentration 50
Molecules
Lipozyme

Keywords

  • Anomers
  • Anticancer activity
  • Lipozyme® TL IM
  • O-Aryl ribofuranosides
  • Regio- and stereoselective deacetylation

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

O-Aryl α,β-d-ribofuranosides : Synthesis & highly efficient biocatalytic separation of anomers and evaluation of their Src kinase inhibitory activity. / Sharma, Raman K.; Singh, Sukhdev; Tiwari, Rakesh; Mandal, Deendayal; Olsen, Carl E.; Parmar, Virinder S.; Parang, Keykavous; Prasad, Ashok K.

In: Bioorganic and Medicinal Chemistry, Vol. 20, No. 23, 01.12.2012, p. 6821-6830.

Research output: Contribution to journalArticle

Sharma, Raman K. ; Singh, Sukhdev ; Tiwari, Rakesh ; Mandal, Deendayal ; Olsen, Carl E. ; Parmar, Virinder S. ; Parang, Keykavous ; Prasad, Ashok K. / O-Aryl α,β-d-ribofuranosides : Synthesis & highly efficient biocatalytic separation of anomers and evaluation of their Src kinase inhibitory activity. In: Bioorganic and Medicinal Chemistry. 2012 ; Vol. 20, No. 23. pp. 6821-6830.
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