A chiral synthesis of a series of hexahydroisobenzofuran (HIBF) nucleosides has been accomplished via glycosylation of a stereo-defined (syn-isomer) sugar motif 16 with the appropriate silylated bases. All nucleoside analogs were obtained in 52-71% yield as a mixture of alpha- and beta-anomeric products increasing the breadth of the novel nucleosides available for screening. The structure of the novel bicyclic HIBF nucleosides was established by a single crystal X-ray structure of the beta-HIBF thymine analog 22b. Furthermore, the sugar conformation for these nucleosides was established as N-type. Among the novel HIBF nucleosides synthesized, twenty-five compounds were tested as inhibitor of HIV-1 in human peripheral blood mononuclear (PBM) cells and seven were found to be active (EC(50) = 12.3-36.2 microM). Six of these compounds were purine analogs with beta-HIBF inosine analog 22o being the most potent (EC(50) = 12.3 microM) among all compounds tested. The striking resemblance between didanosine (ddI) and 22o may explain the potent anti-HIV activity.
A chiral an class="Gene">synthesis of a series of hexahydroisobenzofuran (HIBF) nucleosides has been accomplished via glycosylation of a stereo-defined (syn-isomer) sugar motif 16 with the appropriate silylated bases. All nucleoside analogs were obtained in 52-71% yield as a mixture of alpha- and beta-anomeric products increasing the breadth of the novel nucleosides available for screening. The structure of the novel bicyclicHIBF nucleosides was established by a single crystal X-ray structure of the beta-HIBF thymine analog 22b. Furthermore, the sugar conformation for these nucleosides was established as N-type. Among the novel HIBF nucleosidessynthesized, twenty-five compounds were tested as inhibitor of HIV-1 in human peripheral blood mononuclear (PBM) cells and seven were found to be active (EC(50) = 12.3-36.2 microM). Six of these compounds were purine analogs with beta-HIBF inosine analog 22o being the most potent (EC(50) = 12.3 microM) among all compounds tested. The striking resemblance between didanosine (ddI) and 22o may explain the potent anti-HIV activity.
Authors: V E Marquez; C K Tseng; H Mitsuya; S Aoki; J A Kelley; H Ford; J S Roth; S Broder; D G Johns; J S Driscoll Journal: J Med Chem Date: 1990-03 Impact factor: 7.446
Authors: Kyeong Lee; Yongseok Choi; Giuseppe Gumina; Wen Zhou; Raymond F Schinazi; Chung K Chu Journal: J Med Chem Date: 2002-03-14 Impact factor: 7.446
Authors: Yongseok Choi; Clifford George; Maria J Comin; Joseph J Barchi; Hak Sung Kim; Kenneth A Jacobson; Jan Balzarini; Hiroaki Mitsuya; Paul L Boyer; Stephen H Hughes; Victor E Marquez Journal: J Med Chem Date: 2003-07-17 Impact factor: 7.446
Authors: Frédéric Jeannot; Gilles Gosselin; David Standring; Martin Bryant; Jean Pierre Sommadossi; Anna Giulia Loi; Paolo La Colla; Christophe Mathé Journal: Bioorg Med Chem Date: 2002-10 Impact factor: 3.641
Authors: K C Nicolaou; Shelby P Ellery; Fatima Rivas; Karen Saye; Eric Rogers; Tyler J Workinger; Mark Schallenberger; Rommel Tawatao; Ana Montero; Ann Hessell; Floyd Romesberg; Dennis Carson; Dennis Burton Journal: Bioorg Med Chem Date: 2011-07-23 Impact factor: 3.641
Authors: Saúl Martínez-Montero; Susana Fernández; Yogesh S Sanghvi; Emmanuel A Theodorakis; Mervi A Detorio; Tamara R McBrayer; Tony Whitaker; Raymond F Schinazi; Vicente Gotor; Miguel Ferrero Journal: Bioorg Med Chem Date: 2012-09-23 Impact factor: 3.641