1-3-D-arabinofuranosylcytosine

The resulting semisoiid was triturated thoroughly with absolute methanol, and the resulting suspension was chilled at 0°C. A pale tan solid that separated was collected on a filter and washed repeatedly with methanol. After washing with anhydrous ether, there was obtained 430 mg of 1-(3-D-arabinofuranosylcytosine. 

The DNA polymerase of several tumors incorporated nucleotides of both the a- and 0-anomers. The synergistic effects against leukemia L1210 observed with the combination of 1-3-D-arabinofuranosylcytosine (ara-C) and thioguanine (TG) appear to be due in part to the subadditive toxicity of the combination, which may result from a decrease in incorporation of TG into DNA caused by inhibition of the DNA polymerase of normal... 

B) Preparation of 1-0-D-Arabinofuranosylcytosine In a glass liner, a mixture of 1.16 g (3.0 mmol) of 1-(2,3,5-tri-0-acetyl-(3-D-arabinofuranosyl)-4-thiouracil prepared in (A) and about 60 ml of absolute methanol which had been saturated with anhydrous ammonia at 0°C was heated in a steel bomb at 98° to 105°C for 35 hours. After cooling to about 25°C and venting the bomb, the dark solution was filtered into a round-bottom flask. The methanol and excess ammonia were then removed under reduced pressure at about 25°C. The residual syrup was dissolved in absolute methanol, and the methanol was removed under reduced pressure at a bath temperature of about 40°C. This procedure of dissolving in absolute methanol and removing the solvent was repeated, and the residue was held under reduced pressure at a bath temperature of 45°C for 12 hours. 

Heinemann V, Hertel LW, Grindey GB, et al. Comparison of the cellular pharmacokinetics and toxicity of 2, 2 -difluorodeoxycytidine and 1-beta-D-arabinofuranosylcytosine. Cancer Res 1988 48(14) 4024-4031. 

Tri-O-benzyl-D-arabinofuranosyl chloride (15), presumably of the a configuration, has been used18 in the synthesis of 1-j8-d-arabinofuranosylcytosine (16) and l-/9-D-arabinofuranosyl-5-trifluoro-methyluracil (17). In this case, the Hilbert-Johnson reaction has been performed at room temperature in methylene chloride as solvent. The unusual benzyl protecting groups were removed smoothly by hydro-... 

Recently, we further modified NOAC by the synthesis of new duplex drugs by combination of the clinically used cancer drugs ara-C, 5-fluorodeoxyuridine (5-FdU) and the highly active new compound ethynylcytidine (l-(3-C-ethynyl-P-D-ribopentofuranosyl)-cytosine, ETC) with NOAC, yielding the heterodinucleoside phosphates arabinocytidylyl- N -octadecyl-1 -P-D-arabinofuranosyl-cytosine (ara-C-NOAC), 2 -deoxy-5-fluorouridylyl-N -octadecyl-l-P-D-arabinofiiranosylcytosine (5-FdU-NOAC) and ETC-NOAC ( 3 -C-ethynylcytidylyl-(5 5 )- octadecyl-1-p-D-arabinofuranosylcytosine) as shown in Fig. 2 (28-32). 

Horber DHC, Schott H, Schwendener RA (1995) Cellular pharmacology of a liposomal preparation of N -hexadecyTl- 3-D-arabino-furanosylcytosine, a lipophilic derivative of 1-P-D-arabinofuranosylcytosine. Br J Cancer 71 957-962... 

Methylcytidine (correction to previous paper), platinum complex of cytidine 3 -phosphate, l- 3-D-arabinofuranosylcytosine 5 -phosphate (2 independent analyses), 2,2 -anhydro-l-/3-D-arabinofuranosyl-5-dimethylsulphonio-6-oxocytosine chloride, 2,2 -anhydro-l-(3, 5 -di-0-acetyl-j3-D-arabinofuranosyl)-5-chloro - 6 - oxocy tosine, 2,l -anhy dro -1 - - D -arabinofuranosylcy tosine 2 5 -diphosphate, and 6,2 -anhydro-1 - 3-D-arabinofuranosyl-6-hydroxycytosine. Adenosine 5 -triphosphate disodium salt, adenosine 5 -methylphosphate, adenosine 5-methylphosphonate, 8-methyladenosine 3-phosphate, 2-aza-adenosine, 9-ce-D-arabinofuranosyladenine, 8,2 -anhydro-9- 3-D-arabino-... 

Beranek et al. (82) described the synthesis of 1-beta-D-arabinofuranosylcytosine and the TLC of 2, 3, 5 -Tri-O-l-B-D-arabinosyluracil, 3-B-D-arabinosyluracil, 2, 3, 5 -Tri-0-acetyluradine, several arabinosylcytosine derivatives, cytidine and several acetylcytidine derivatives using 5 different solvent systems including ethyl acetate-methanol (1 1) on Silufol UV254. 

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. ... 

Preliminary studies with azauridine suggest that this material was effective for the treatment of herpes simplex and zoster infections of the human eye (69). Rabbits infected with vaccinia virus vaccine were com-pletely protected from pustule formation and erythema by 2-3 grams of compound injected IV (70). This material apparently has a low order of toxicity. 5-Bromo-2-deoxyuridine was found to inhibit a new virus, equine herpes 3, in rabbit kidney cells as well as pseudorabies, a DMA. virus, whereas vesicular stomatitis, an RNA virus, was resistant (71). A large number of nucleosides have been synthesized and tested in various systems for antiviral activity. 1-p-D-Arabinofuranosylcytosine (cytarabine ara-C) blocked DNA synthesis of herpes-infected cells (72) while a number of structurally related compounds showed some antiviral activity, although less than the parent compound (73,74,75,76). It is still too early to determine the ultimate value of these newer agents as "antiviral" drugs. 

Figure 1 Chemical structures of the 5 —>5 phosphodiester duplex drugs Ara-C-NOAC, mol. wt. 801g/mol, 5-FdU-NOAC, mol. wt. 804g/mol, and ETC-NOAC, mol. wt. 825g/mol. Abbreviations-. Ara-C-NOAC, arabinocytidylyl-(5 —>5 )-lSr -octadecyl-l-P-D-arabinofuranosylcytosine 5-FdU-NOAC, 2 -deoxy-5-fluorouridylyl-(5 5 )-N" -octadecyl-l-P-D-arabinofuranosylcytosine ETC-NOAC, 3 -C-ethynylcytidylyl-(5 5 )-N" -octadecyl-l-P-D-arabinofuranosylcytosine.

I47T/N210D <1> (<1>, clones harbouring the mutant enzyme are more sensitive to 3 -azido-2 ,3 -dideoxythymidine and /1-D-arabinofuranosylcytosine... 

Additional information <1> (<1>, the deletion mutants rDm-dNKAClO and rDm-dNKAC20 show the same substrate activity pattern as the recombinant wild-type enzyme. Relative phosphorylation of 2 -deoxycytidine and 2-chloro-2 -deoxyadenosine increases with increasing C-terminal truncation. The relative activities of rDm-dNKAClO and rDm-dNKAC20 with deoxyribonucleosides remains largely unchanged, whereas there is a substantial decrease in the phosphorylation of the purine ribonucleosides adenosine and guanosine, as well as of all dideoxyribonucleosides and 3 -azido-2 ,3 -dide-oxythymidine. The relative activities with the pyrimidine ribonucleosides and l-/l-D-arabinofuranosylcytosine and l-/i-D-arabinofuranosylthymine are not affected by the C-terminal deletions [4]) [4]... 

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