Synthesis, conformational study and antiviral activity of l-like neplanocin derivatives. Issue 18 (15th September 2017)

• Record Type: Journal Article
• Authors: Chen, Qi; Davidson, Amber
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 18(2017)
• Page Start: 4436
• Page End: 4439
• Publication Date: 2017-09-15
• Subjects: Carbocyclic nucleosides -- l-like nucleosides -- Nucleoside conformation -- Neplanocin -- Antiviral; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.08.009
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Thel -like enantiomer of 9-(trans-2′, trans-3′-dihydroxycyclopent-4′-enyl)-3-deazaadenine (DHCDA) (1 ), its 3-deaza-3-bromo derivative (3 ), and the conformational restricted methanocarba (MC) nucleoside analogues (2 and4 ) were synthesized. X-ray crystal structures showed the L isomer MC analogue4 adopts a similar North-like locked conformation as conventional D-MC nucleosides, while the DHCDA analogue3 preferred south-like conformer. Compounds1 and4 showed potent antiviral activity against norovirus, while compound2 and3 were less potent or inactive. The conformational behavior of "sugar" puckering (north/south) and nucleobase orientation (syn /anti) may contribute to the antiviral activity differences. For compound3, antiviral activity was also found against Ebola virus.