Synthesis of 3’, 5’-cyclic diguanylic acid (c-di-GMP) as mucosal vaccine adjuvant and bacterial second messenger
The present study describes the synthesis of 3’,5’- cyclic diguanylic acid (c-di-GMP), attempts were made to synthesize guanosine bearing a 2’-O-(hexyn-6-yl)- and 2’-O-(6-azidohexyl)-modification using 2,6-diaminopurine riboside as starting material. The synthesis of 2’-O-(hexyn-6-yl) guanosine started with the alkylation of 2,6-diaminopurine riboside with 6-iodo-1-hexyne, which gave a mixture of 2’- and 3’-O-alkylated 2,6-diaminopurine riboside. Treatment of this product with isobutyryl chloride, followed by ammonium hydroxide gave N2-isobutyryl-2’-O-2’-O-(hexyn-6-yl)-2,6-diaminopurine riboside. Subsequent deamination reaction was carried out with sodium nitrite in a mixed solvent gave the desired N2-isobutyryl-2’-O-2’-O-(hexyn-6-yl) guanosine. N2-Isobutyryl-2’-O-(6-azidohexyl) guanosine was also obtained in the similar manner. Synthesis of a second building block, a suitably protected guanosine H-phosphonate was also attempted using guanosine as starting material. Experimental and spectral data are provided for new compounds.