Convenient Synthesis of a Propargylated Cyclic (3′-5′) Diguanylic Acid and its 'Click' Conjugation to a Biotinylated Azide
| Autor: | Andrzej Grajkowski, Alexei Gapeev, Serge L. Beaucage, Christian Schindler, Jacek Cieślak |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Azides
Guanine Biomedical Engineering Guanosine Monophosphate Molecular Conformation Pharmaceutical Science Guanosine Biotin Bioengineering Stereoisomerism Medicinal chemistry Article chemistry.chemical_compound Guanosine monophosphate Organic chemistry Biotinylation Pharmacology Organic Chemistry Ribonucleoside Cycloaddition chemistry Click chemistry Click Chemistry Azide Biotechnology |
| Popis: | The ribonucleoside building block, N2-isobutyryl-2′-O-propargyl-3′-O-levulinyl guanosine (Scheme 1), was prepared from commercial N2-isobutyryl-5′-O-(4,4′-dimethoxytrityl)-2′-O-propargyl guanosine in a yield of 91%. The propargylated guanylyl(3′-5′)guanosine phosphotriester shown in Scheme 2 was synthesized from the reaction of N2-isobutyryl-2′-O-propargyl-3′-O-levulinyl guanosine with N2-isobutyryl-5′-O-(4,4′-dimethoxytrityl)-2′-O-tert-butyldimethylsilyl-3′-O-[(2-cyanoethyl)-N,N-diisopropylaminophosphinyl] guanosine and isolated in a yield of 88% after P(III) oxidation, 3′-/5′-deprotection and purification. The propargylated guanylyl(3′-5′)guanosine phosphotriester was phosphitylated using 2-cyanoethyl tetraisopropylphosphordiamidite and 1H-tetrazole and was followed by an in situ intramolecular cyclization to give a propargylated c-di-GMP triester (Scheme 3), which was isolated in a yield of 40% after P(III) oxidation and purification. Complete N-deacylation of the guanine bases and removal of the 2-cyanoethyl phosphate protecting groups from the propargylated c-di-GMP triester were performed by treatment with aqueous ammonia at ambient temperature. The final 2′-desilylation reaction was effected by exposure to triethylammonium trihydrofluoride to give the desired propargylated c-di-GMP diester, the purity of which exceeded 95% (Figure 2B). Biotinylation of the propargylated c-di-GMP diester was easily accomplished through its cycloaddition reaction with a biotinylated azide derivative (Scheme 4) under click conditions to produce the biotinylated c-di-GMP conjugate of interest in an isolated yield of 62%. |
| Databáze: | OpenAIRE |
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