Oxadiazole C-Nucleosides

5-Oxadiazole C-Nucleosides and Their Reverse AND Acyclo Analogs 

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Oxidative cyclization of the semicarbazone 737 with lead tetraacetate gave the carbocyclic analog 738 of 1,3,4-oxadiazole C-nucleosides (75TL985 76CJC861) (Scheme 198). 

The tetrazole acydo C-nucleoside 749 (Section XXII,C) afforded the 1,3,4-oxadiazole acyclo analogs 752 upon treatment with acid anhydrides or acid chlorides (76MI12 91MI14 92MI1 94AQ130) (Scheme 202). 

Addition reactions to unsaturated C-glycosides have continued to be utilized to synthesize C-nucleosides. Thus 2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl cyanide with sodium azide-ammonium chloride in DMF gave the tetrazole (72) in 72% yield. Treatment of (72) with acetic anhydride gave the 1,3,4-oxadiazole nucleoside (73). The benzothiazole (74) was obtained from the ribosyl cyanide by reaction with 2-aminothiophenol. Analogous compounds were derived from jS-D-ribo-, 8-D-xylo-, and j3-D-galactopyranosyl cyanides. A similar reaction has been used by a different group to synthesize a-D-arabinosyl tetrazole (75). Reaction of 3,4-di-0-benzoyl-2,5-anhydro-D-... 

The acyclic C-nucleoside analogues of 1,3,4-thiadiazoles 247 were prepared by the oxidative cyclization of the thiosemicarbazones 248 (X = S) with iron(III) chloride (86JPR1 87BCJ3405). The respective oxadiazole analogues were prepared by the oxidation of the acetate of 248 (X = O) with iodine (72MI1). Both of the aroylhydrazones and thiosemicarbazones... 

Dehydrative cyclization of the 1-aldonoylsemicarbazide 734 gave the 2-amino-l,3,4-oxadiazol-5-yl C-nucleoside 735. The thiosemicarbazide analog 736 of 734 was also cyclized to 735 by the action of lead(II) oxide (86CCC1311) (Scheme 197). 

Molfatt s group has used the 2,5-anhydro-D-allose tribenzoate (30) to prepare D-ribofuranosyl-isoxazoles (Scheme 14),-1,2,4-oxadiazoles, and -pyrazoles (Scheme 15). Related approaches to the synthesis of C-nucleosides have been described e.g. the final stages of a synthesis of 3-methylshowdomycin are shown in Scheme 16, and the sugar derivative (31) was converted into the anomeric... 

The oxadiazole 140, related to ribavirin, has been prepared by cyclization of a known sugar-protected amidoxime. The 4 -thio-analogues 141 (X = O, S) of furanfurin and thiophenfurin (Vol. 29, p. 283), themselves analogues of ribavirin, have been prepared by condensation between the heterocycles, as their ethyl esters, with 0-protected derivatives of 4 -thioribofuranosyl acetate. The thiophene compound ( thiophenthiofurin ) had cytotoxicity towards cancer cell lines, but less so than thiophenfurin. A previously-known 2,5-anhydroglucose derivative 142 has been converted to the pyrazole 143, and some related compounds. Some pyrazole iso-C-nucleosides are mentioned in Chapter 2. Various 3-cyano-2-(P-D-ribofuranosyl)-1,5-benzodiazepines have been prepared by a novel ring transformation of 5-(tri-0-benzoyl-p-D-ribofuranosyl)isoxazole-4-carbaldehyde. ... 

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