Synthesis of 2′‐deoxyribofuranosyl indole nucleosides related to the antibiotics SF‐2140 and neosidomycin

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 (5). Thus, treatment of the sodium salt of 4‐methoxy‐1H‐ indol‐3‐ylacetonitrile (4a) with 5 provided the blocked nucleoside, 4‐methoxy‐1‐(2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐β‐ D‐erythropentofuranosyl)‐1H‐indol‐3‐ylacetonitrile (6a), which was treated with sodium methoxide to yield the SF‐2140 analog, 4‐methoxy‐1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐1H‐indol‐3‐ ylacetonitrile (7a). The neosidomycin analog (8) was prepared by treatment of the sodium salt of 1H‐indol‐3‐ylacetonitrile (4b) with 5 to obtain the blocked intermediate 1‐(2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐β‐D‐erythropentofuranosyl) −1H‐indol‐3‐ylace‐tonitrile (6b) followed by sodium methoxide treatment to give 1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐1H‐ indol‐3‐ylacetonitrile (7b) and finally conversion of the nitrile function of 7b to provide 1‐(2‐deoxy‐β‐D‐ erythropentofuranosyl)‐1H‐indol‐3‐ylacetamide (8). In a similar manner, indole (9a) and several other substituted indoles including 1H‐indole‐4‐carbonitrile (9b), 4‐nitro‐1H‐indole (9c), 4‐chloro‐1H‐indole‐2‐carboxamide (9d) and 4‐chloro‐1H‐indole‐2‐carbonitrile (9e) were each glycosylated and deprotected to provide 1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐1H‐indole (11a), 1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐1H‐indole‐4‐ carbonitrile (11b), 4‐nitro‐1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐1H‐indole (11c), 4‐chloro‐1‐(2‐deoxy‐β‐D‐ erythropentofuranosyl)‐1H‐indole‐2‐carboxamide (11d) and 4‐chloro‐1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐ 1H‐indole‐2‐carbonitrile (11e), 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 (16, 1,3,7‐trideaza‐2′‐deoxyadenosine).