Thiadiazole C-Nucleosides

The single example of this class that is known so far (555) has been synthesized as a stable precursor for the thermolytic in situ production of the allonoylnitrile A -sulfide 556 the latter is the reactive species in the synthesis of isothiazole (Section XI Scheme 149) and 1,2,4-thiadiazole C-nucleosides (Section XIX Scheme 203). The 5-(tri-0-benzoyl-/3-D-ribofuranosyl)-l,3,4-oxathiazol-2-one (780) was obtained from the 2,5-anhydro-D-allonic acid amide 779 by heating with chlorocarbonylsulfenyl chloride (84JOC2165 91MI21) (Scheme 213). 

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... 

Oxidative cyclization of aWe/iydo-sugar 5-alkylhydrazonecarbodithioates (772) with bromine in acetic acid and anhydrous sodium acetate gave the corresponding 2-(alditol-l-yl)-5-alkylthio-l,3,4-thiadiazoles 770. In addition, cyclocondensation of 772 by heating with acetic anhydride gave the 1,3,4-thiadiazoline C-nucleosides 773 (97UP1) (Scheme 210). 

D-Gluconoylthiosemicarbazide (774) underwent dehydrocyclization by heating with acetic anhydride and zinc chloride to the 2-acetamido-l,3,4-thiadiazole acyclo C-nucleoside 775. The latter was deacetylated and transformed to the 5-ureido derivative 760 (94MI10) (Scheme 211). 

Irradiation of the pyridyl thioglycoside (73) caused a complex isomerization to give the jS-iV-bonded compound (74) as well as the a- and j8-C-nucleosides bonded through C-3 and C-5. All were isolated in low yield only. The 1,2,4-thiadiazole thioglucoside (75) has been reported,and the acid- and almond /3-glucosidase-catalysed hydrolysis of the purine compound (76) and its 2 -deoxy analogue have been investigated. As expected, the latter is the more sensitive in acid solution, but the former is the better enzyme substrate. ... 

An Intermediate nitrile sulphide Is presumed to be Implicated in the synthesis of the thiadiazole and thiazole C-nucleosides... 

Zhan P, liuX, CaoY, Wang Y, Pannecouque C, De Qercq E (2008) 1,2,3-thiadiazole thioac-etamUdes as a novel class of potent HlV-1 non-nucleoside reverse transcriptase inhibitors. Bioorg Med Chem Lett 18 5368-5371... 

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