Nucleosides acyclic analogues, preparation

Cyclic phosphonate analogues of PMEA (36) have been obtained after stereoselective cyclisation of an acyclic phosphonyl intermediate to the phos-phonyltetrahydrofuran nucleoside derivative. A series of cyclopropylphos-phonate analogues (37) has been synthesised stereoselectively via intramolecular epoxide opening reaction of y,5-epoxyalkanephosphonates with subsequent Mitsunobu coupling reaction to purine bases. Acyclic phosphonate derivatives of thymine (38-43) have been prepared and evaluated as multisubstrate analogue inhibitors of Escherichia coli thymidine phosphor-... 

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... 

The 3-j3-D-arabinofuranosyl pyrazole derivative (33) has been synthesized from D-mannose by the procedure outlined in Scheme 9 on deprotection with ammonia, (33) epimerized to the -D-ribofuranosyl isomer. 2,5-Anhydro-D-allonic acid derivatives have been used to synthesize the C- ym-triazoloribo-nucleosides (34) and (35) by condensation with heterocyclic hydrazine derivatives. The diazoketone (36), prepared conventionally from the acid, has been used to prepare the thiazole analogue (37) of ribavirin via the intermediate a-bromomethyl ketone (38) by condensation with an imido-thio-oxalic acid derivative,and the indazole nucleoside analogue (39) by cyclization with benzyne (Scheme 10). An acyclic diazoketone analogously prepared from D-ribonic acid similarly gave a C-ribonyl-indazole with benzyne, which could be... 

McGuigan and coworkers [19] prepared a range of acyclic 5 -dialkyl phosphate triester derivatives of the anticancer drug ara-C (11, B = cytosyl, R = Et, n-Pr, n-Bu, n-pentyl or n-hexyl). These triesters inhibited DNA synthesis and their efficacy improved with increasing lipophilicity. This result suggested that these triesters were membrane permeable however, their mechanism of inhibition of DNA synthesis was unresolved. In a similar study, inhibition of DNA synthesis also increased as the lipophilicity of the phosphate triester of the anti-viral nucleoside ara-A (11, B = adenyl, R = Et, n-Pr, n-Bu or n-pentyl) increased [20]. The dibutyl phosphinate analogue... 

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