Total and stereospecific synthesis of cadeguomycin, 2′deoxycadeguomycin, ara-cadeguomycin, and certain related nucleosides

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Abstract
A total and stereospecific synthesis of cadeguomycin (1), ara-cadeguomycin (2), and 2′-deoxycadeguomycin (3) has been accomplished from the novel aglycones 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (11) or methyl 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (13). Ring annulation of 2,6-diaminopyrimidin-4(3H)-one (6) with methyl chloro(formyl)acetate (7) in the presence of NaOAc provided a mixture of two products (8) and (9), from which the desired methyl 2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (9) was separated and converted into the key intermediates (11) and (13). Reaction of the sodium salt of (11) with 2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranosyl chloride (14) gave the corresponding protected nucleoside (15). Deprotection of (15) provided (16), which on treatment with NH4OH–H2O2, followed by saponification, gave the target nucleoside (3) in good yield. Compound (3) was also prepared from compounds (13) and (14) by a similar sequence of reactions. Glycosylation of the sodium salt of (11) with 5-O-t-butyldimethylsilyl-2,3-O-isopropylidene-α-D-ribofuranosyl chloride (22) gave protected nucleoside (23), which on treatment with 4M-KOH followed by deisopropylidenation afforded cadeguomycin (1). Similarly, glycosylation of the sodium salt of (11) with 2,3,5-tri-O-benzyl-α-D-arabinofuranosyl chloride (27) furnished the corresponding glycosylated product (28), which on debenzylation and hydrolysis produced ara-cadeguomycin (2). Selective functional-group transformations of compound (16), (21), and (24) furnished several 2-amino-4,5-disubstituted pyrrolo[2,3-d]pyrimidine nucleosides.

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