title: Regioselective Synthesis of Pyrazolo[3,4-D]Pyrimidine Based Carbocyclic Nucleosides as Possible Antiviral Agent.
abstract: Carbocyclic nucleosides are considered as nucleoside mimetic having high therapeutic potentials, however diverse exploration is still limited due to their synthetic difficulties. The major challenges are associated with the preparation of new base and carbocyclic sugar key intermediates. The modified base may provide conformational advantage to achieve better nucleoside mimetics and may also help in increasing the drug-like properties. In this manuscript, we report the use of acetamidine hydrochloride to synthesize 6-methyl-4-amino-pyrazolo[3,4-d]pyrimidine base and regioselective synthesis of six new carbocyclic nucleosides (6a-f) for antiviral evaluation. Theoretical investigations were carried out on the basis of thermodynamic and kinetic stability using MM based energy optimizations and QM based transition state search for the significant regioselectivity, which was further experimentally analyzed by NOE and UV spectroscopy.
authors.affiliation: a Department of Chemistry , Birla Institute of Technology , Mesra , Ranchi -835215 , India.
authors.forename: Mohan
authors.initials: M
authors.lastname: Kasula
authors.affiliation: b Chemistry Services, GVK Biosciences Pvt. Ltd., IDA Uppal , Hyderabad 500039 , India.
authors.forename: Ramakrishnamraju
authors.initials: R
authors.lastname: Samunuri
authors.affiliation: a Department of Chemistry , Birla Institute of Technology , Mesra , Ranchi -835215 , India.
authors.forename: Harapriya
authors.initials: H
authors.lastname: Chakravarty
authors.affiliation: a Department of Chemistry , Birla Institute of Technology , Mesra , Ranchi -835215 , India.
authors.forename: Chandralata
authors.initials: C
authors.lastname: Bal
authors.affiliation: c Division of Antiviral Chemotherapy , Center for Chronic Viral Diseases, Kagoshima University , Kagoshima , Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
authors.affiliation: b Chemistry Services, GVK Biosciences Pvt. Ltd., IDA Uppal , Hyderabad 500039 , India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Jha
authors.affiliation: a Department of Chemistry , Birla Institute of Technology , Mesra , Ranchi -835215 , India.
authors.forename: Ashoke
authors.initials: A
authors.lastname: Sharon
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides
keywords: Mitsunobu reaction; antiviral agent; conformation; neplanocin; nucleoside mimetic