Synthesis of 2'-deoxyribofuranosyl indole nucleosides related to the antibiotics SF-2140 and neosidomycin

Article abstract of DOI:10.1002/jhet.5570250202

The 2'-deoxyribofuranose analog of the naturally occurring antibiotics SF-2140 and neosidomycin were prepared by the direct glycosylation of the sodium salts of the appropriate indole derivatives, with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythropentofuranose. Thus, treatment of the sodium salt of 4-methoxy-1H-indol-3-ylacetonitrile with 5 provided the blocked nucleoside, 4-methoxy-1-(2-deoxy-3,5-di-O-p-toluoyl-β-D-erythropentofuranosyl)-1 -indol-3-ylacetonitrile, which was treated with sodium methoxide to yield the SF-2140 analog, 4-methoxy-1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indol-3-ylacetoni rile. The neosidomycin analog was prepared by treatment of the sodium salt of 1H-indol-3-ylacetonitrile with 5 to obtain the blocked intermediate 1-(2-deoxy-3,5-di-O-p-toluoyl-β-D-erythropentofuranosyl)-1H-3-ylacet nitrile followed by sodium methoxide treatment to give 1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indol-3-ylacetonitrile and finally conversion of the nitrile function of 7b to provide 1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indol-3-ylacetamide. In a similar manner, indole and several other substituted indoles including 1H-indole-4-carbonitrile, 4-nitro-1H-indole, 4-chloro-1H-indole-2-carboxamide and 4-chloro-1H-indole-2-carbonitrile were each glycosylated and deprotected to provide 1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole, 1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole-4-carbonitrile, 4-nitro-1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole, 4-chloro-1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole-2-carboxami e and 4-chloro-1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole-2-carbonitr le, respectively. The 2'-deoxyadenosine analog in the indole ring system was prepared for the first time by reduction of the nitro group of 11c using palladium on carbon thus providing 4-amino-1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole (1,3,7-trideaza-2'-deoxyadenosine).