One Man’s Trash is Another Man’s Treasure:Development of Antiviral Reagents
소속 :
연사 : Prof. 조종현(동아대학교)
일시 : 2019-05-16 16:30 ~
장소 : 500동 목암홀
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).
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).
