Uracil -2,2 anhydro-, preparation

The first preparation of a secondary deoxyfluoro sugar, other than by total synthesis, involved the cleavage of 2,2 -anhydro-3-( 8-D-arabino-furanosyl) uracil (3) to give 3-(2-deoxy-2-fluoro-/3-D-ribosyl) uracil. This reaction, which can be extended to cleavage by hydrogen bromide or chloride, is at pr ent the only route to 2-deoxy-2-fluoro-D-ribose deriva-... 

Compounds of the type 65 have been prepared by opening of the epoxide ring of l-(2,3-anhydro-5-0-trityl-P-D-lyxofuranosyl)uracil with a variety of carbon nucleophiles such as ethynyl lithium, vinylmagnesium bromide/cuprous iodide and l,3-dithian-2-yl lithium. These reactions afforded regioselectively 3 -C-substituted-3 -deoxy-P-D-arabinofuranosyl nucleosides 69-71 in 10-68% yield [84, 87] (Fig. 12). These intermediates have been transformed into a variety of other 3 -C-substituted-3 -deoxy-arabinofuranosyl uridines 72-77 [84]. 9-(3-Deoxy-3-C-methyl-P-D-xylofuranosyl)adenine has been prepared by glycosidation reaction of a 3-deoxy-3-C-methyl-P-D-xy/ofuranosyl chloride with adenine [90]. 

Numerous syntheses have also been reported for arabinofuranosyl nucleoside analogues, prepared either conventionally from arabinofuranosyl derivatives or via 2,2-anhydro-nucleosides obtained from appropriate ribonucleosides. 5-Aza-cytosine-D-arabinoside has been synthesized and found to show similar antiviral activity to Ara-C(arabinosyl-cytosine). 7-a-, 7-<3-, 9-0 -, and 9- 3-arabino-furanosyl derivatives of 3-deazaguanine have also been prepared, but none showed any anti-tumour activity. 9-(o -D-Arabinofuranosyl)-8-aza[2- C]-adenine, 7-(/3-D-arabinofuranosyl)-pyrrolo[2,3-d]pyrimidine-4(3//)-one (15)," l-(a-D-arabinofuranosyl)- and l-(/3-D-xylofuranosyl)-4-nitropyrazole, and Ot-arabino-nucleosides of 5-fluoro-cytosine and -uracil derivatives have also been prepared. An improved synthesis of 9-(/3-D-arabinofuranosyl)-2-fluoro-adenine has been reported. The ratio of o to 3 anomers obtained by phase-transfer reaction of 2,3,5-tri-O-benzyl-D-arabinofuranosyl bromide with 6-chloro-2-thiomethyl-7-deazapurine varied with the quaternary ammonium salt used as a catalyst, although the jU-anomer predominated in every case. 2,2-Anhydro-nucleosides have been used to prepare l-j3-D-arabinofiiranosyl derivatives of 5-alkylthio-uracils, 5-ethyl-cytosine, and 5-ethyl-uracil, 8-alkylamino-purines, and 2-aralkylamino-l,4-dihydro-4-imino-pyrimidine hydrochlorides (16). ... 

Uracil and cytosine derivatives of 4-thio-DL-erythrofuranose and adenine and guanine nucleoside analogues of 4-thio-D-ribofuranose, 4-thio-D-xylofuranose, and 5-thio-D-xylopyranose have been reported. Treatment of 2,2 -anhydro-cytosine with phosphorus pentasulphide gave the cyclic thiophosphate derivatives (49), which was used to prepare other 2 -thio-cytidine derivatives. The... 

Uridine 2, 3 -episulphide and an analogous D-/yxo 2, 3 -episulphide have been prepared from l-(2,3-anhydro-5-0-benzoyl-p-D-lyxofuranosyl)uracil and 2,2 -S-anhydro-l-p-D-arabinofuranosyl-2-mercaptouracil, respectively, by conventional procedures. Treatment of 2, 3 -anhydroinosine with dilute sodium hydroxide solution at 80°C gave the 3, 5-cyclonucleoside-4-carboxamide (604). ... 

A convenient synthesis of 5 -deoxy-2-fluoroadenosine from guanosine has been reported. Ring-opening of l-(2,3-anhydro-P-D-lyxofuranosyl)-cytosine and -uracil with ammonium bromide, iodide, azide, and thiocyanate in refluxing ethanol has been used to prepare l-(3-deoxy-3-halogeno-P-D-arabinofuranosyl)-... 

The synthesis of 1-g-D-arabinofuranosylcytosine and some derivatives has been reviewed. Syntheses reported for other ara-nucleosides include spongo-uridine, ara-tubercidin, and the a- and -anomers of ara-7-deazaguanosine prepared by phase-transfer catalysis. Conventional methods have been used to prepare D-glucofuranose derivatives of uracil and thymine,a g-D-glucopyranosyl derivative of nicotine, and 9-(3,4-anhydro-6-deoxy-a-L-talopyranosyl)-6-benzoyl-adenine from L-rhamnose. ... 

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