One Man’s Trash is Another Man’s Treasure:Development of Antiviral Reagents

February 25, 2019l Hit 443
Date : May 16, 2019 16:30 ~
Speaker : Prof. Jo Jong Hyun(DongA University)
Location : Mogam Hall, Bldg 500
This seminar consists of two parts. Part I. The development of HCV drug (Sofosbuvir) and HIV agents: Nucleoside and nucleotide prodrug analogs Part II. Efficient synthesis and biological evaluation of carbocyclic nucleoside analogs: Potent biological active agents A practical and convenient method for the synthesis of chiral cyclopentenol derivatives (Ia-b) has been developed as the key intermediate for the synthesis of biologically active carocyclic nucleosides. From D-ribose, the selective protection of allylic hydroxyl group was followed by ring closing metathesis (RCM) reaction with Grubbs’ catalyst II provided a single cyclopentanol (Ia) in 52% yield. The key intermediate was used for the synthesis of unnatural five-membered ring heterocyclic carocyclic nucleosides such as neplanocin A (NPA). The novel structure, 1,2,3-triazolenucleoside (II), exhibited potent antiviral activity (EC500.4μM) against vaccinia virus. In addition, a chiral cyclopentenol derivative (Ib) was used to develop an efficient synthetic route for biologically relevant (-)-5-fluorocarbodine (III), a potent anti-cancer agent. Direct coupling of N6-protected5-fluorouracilwithcyclopentenol(1b), followed by formation of a macrocycle between the base and sugar moiety, via RCM reaction, allowed for a facial selective hydrogenation of the sugar double bond to exclusively give the desired 4’-β-stereoisomer (III).