Synthesis of 3’,5’-cyclic diguanylic acid (cdiGMP) Using 1-(4-chlorophenyl)-4-ethoxypiperidin-4-yl as a Protecting Group for 2’-hydroxy Functions of Ribonucleosides

Abstract We herein report a convenient synthesis of 3′,5′-cyclic diguanylic acid via the modified H-phosphonate approach. The 1-(4-chlorophenyl)-4-ethoxypiperidin-4-yl (Cpep) group was used as protecting group for the 2′-hydroxy functions of ribonucleosides. Complete unblocking of the fully protected 3′,5′-cyclic diguanylic acid gave cdiGMP as a homogeneous compound in an excellent yield. Keywords: Biofilmbacterial signaling pathwayH-phosphonatecyclic ribonucleotideCpep This research was supported by awards from Research Corporation and Canada Foundation for Innovation. The authors thank Professor Colin B. Reese for generous gifts of nucleosides, Tim Jones and Razvan Simionescu for mass spectrometric and NMR analysis, respectively. Notes ∗A system of abbreviations[ Citation 30 ] is followed for protected oligonucleotides in which nucleoside residues and internucleotide linkages are italicized if they are protected in some defined way. In the present context, G′′ represents guanine protected on O-6 with a 2,5-dichlorophenyl group and N-2-protected with a phenylacetyl group; and p(s′) represents an S-phenyl-protected phosphorothioate.