Arabinofuranosyl cytidine

Treatment of the D-arabinofuranosyloxazoline (24) with 1-chloro-l-cyano-ethene gave the 2,2-0-c clonucleosides (25) and (26) (Scheme 6)P 3,5-Di-C)-acyl derivatives of 2,2 -0-cyclo-]3-D-arabinofuranosyl-cytidine have been prepared by reaction of cytidine with the acid chloride or anhydride derivatives of 3-heptyloxypropanoic, 3-dodecyloxypropanoic, and 11-butyrylamino-undecanoic acid the dimeric derivative (27) was also prepared. 

Using a reaction sequence involving dibutylstannylation and displacement of triflate, new 2 -substituted-2 -deoxyarabinofuranosyl adenine derivatives have been prepared (Scheme 12) the products (92) and (93) were converted into the corresponding 2 -amino- and 2 -thio-ara6mo-nucleosides. A communication, with no synthetic details, on the preparation and use of 2 -azido-and 2 -amino-2-deoxy-j8-D-arabinofuranosyl cytidine as cytotoxic agents has been published. ... 

D-lyxopyranosyl nucleosides with hydrogen halides to give the 3 -bromo- or 3 -chloro-3 -deoxy-nucleosides (406), or a mixture of the 2 - and 3 -fluoro-deoxy-nucleosides (407). 9-(3-Deoxy-3-iodo-)3-D-xylofuranosyl)hypoxanthine has been synthesized and converted into 3 -amino-3 -deoxy- and 3, 4 -unsatu-rated nucleosides as shown in Scheme 138. Both l-(2-deoxy-2-fluoro- and 2-chloro-2-deoxy-j8-D-arabinofuranosyl)cytidine have been prepared from the corresponding halogeno-sugar derivatives by standard methods (see Schemes 43 and 46). ... 

Cytidylate reductase, the enzyme that reduces cytidine diphosphate to 2-deoxycytidine diphosphate is inhibited not only by 1- -D-arabinofuranosyl-cytosine, but also by 9 -D-arabinofuranosyladenine [330] and 9-/3-D-arabino-furanosylpurine-6( 1 H)-thione (LXXV) [331-333]. 9-Butylthioguanine (LXXVl), which is catabolized to unidentified excretion products but which is not debutylated, blocks the incorporation of adenine into DNA, but the exact mechanism of this action is unknown [334]. 

S Additional information <3, 7> (<3> enzyme exists in different conformational states with different substrate kinetic properties [9] <3> presumably one common nucleoside acceptor site [15] <3> purine deoxynucleo-side activity inseparably associated with deoxycytidine kinase protein [16] <3> several isozymes cytosolic deoxycytidine kinase I and II, plus mitochondrial isozyme [10] <3> multisubstrate enzyme, that also phos-phorylates purine deoxyribonucleotides [9] <7> enzyme has two separate active sites for deoxycytidine and deoxyadenosine activity [22] <3> reacts with both enantiomers of -deoxycytidine, -deoxyguanidine, -deoxyadenosine, and a-D-deoxycytidine is also substrate [31] <3> reacts with both enantiomers of jS-deoxyadenosine, j3-arabinofuranosyl-adenine and jd-deoxyguanine ]34] <3> remarkably relaxed enantioselectivity with respect to cytidine derivatives in p configuration [36] <3> lack of enantioselectivity for D- and L-analogues of cytidine and adenosine [43]) [9, 10, 15, 16, 22, 31, 34, 43]... 

Syntheses involving standard condensation procedures for heterocyclic bases with amino-sugar derivatives have included the preparation of 2 -azido-, 3 -azido-2 ,5 -diazido-, and 3, 5-diazido-derivatives of arabino-nnAinc, 3 -amino-3-deoxy-adenosine, -uridine, and -cytidine 5-phosphates, 2, 3-bis(2-chloroethyl)-aminophosphoryl-3-amino-3-deoxyadenosine (which has anti-tumour activity), 3-A -methyl-A -nitrosoureido-3-deoxy-adenosine and the corresponding 5-substituted isomer, and 2 -azido-2-deoxy- and 2-amino-2-deoxy-D-arabinofuranosyl-... 

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-... 

Remin M, Shugar D (1973) Crmfoimational analysis of cytidine l-p-D-(arabinofuranosyl) cytosine and their O -methyl derivatives by proton magnetic resonance spectroscopy. J Am Chem Soc 95 8146-8156... 

Cyclocondensation of cytidine with acetylsalicyloyl chloride gave the corresponding 2,2 -anhydro-D"arabinofuranosyl-nucleoside, which was hydrolysed to give ara6/ o-cytidine. ... 

Cytidine 2, 3 -cyclicphosphate, polymeric complexes of Cd" and Cu" and cytidine 5 -phosphate, l-(j8-D-arabinofuranosyl)cytosine Pt complex. Adenosine complexed with 5-bromouracil, iS-methyl-5 -thioadenosine, 2, 3 -0-isopropyIideneadenosine, 2, 3 -0-(2-carboxyethyl)ethylideneadeno-sine, the amino-acid adenosine derivatives (5) and (6) which are constitutents of tRNA, 8-[(2-aminoethyl)amino]adenosine 3, 5 -cyclic phosphate. 8-Iodoguanosine, 2-JV-methylguanosine, a guanosine Hg" complex, 2, 35 -tri-(9-acetyl-6-0-(mesitylenesulphonyl)-guanosine, guanosine 5 -phosphate, Cu" complex. ... 

Cl4H22 On, 9-/3-D-Arabinofuranosyl-8-n-butylaminoadenine, 45B, 501 Cl4H2gNgOi3P 2 H2O, Tris(hydroxymethyl)methylammonium adenosines -diphosphate dihydrate, 46B, 466 Cl4H3sN,NaOi8P2, Sodium cytidine-5 -diphospho-choline pentahydrate, 41B, 511... 

Cytidine has been converted into l-(5-amino-5-deoxy-j8-D-arabinofuranosyl) cytosine by a sequence of reactions involving A-benzoylation, sulphonation, acetylation, displacement with azide ion, e/c., and l-(3-amino-3-deoxy-jS-D-arabinofuranosyl)-6-azauracil was derived from 2, 3 -di-0-methanesulphonyl-5 -O-trityl-6-azauridine via 2,2 - and 2, 3 -anhydro-nucleosides. Other syntheses have been accomplished by the condensation of an appropriately derivatized amino-sugar with either a pyrimidine or purine derivative for example, the Hilbert route was used to prepare l-(2-amino-2-deoxy-a-D-arabino- and -jS-o-xylo-furanosyl)cytosine. > The reactivity of l,3,4,6-tetra-0-acetyl-2-acyl-amido-2-deoxy-j3-D-glucopyranoses in condensation reactions with 2,6-dichloro-purine, theophylline, and 6-benzylaminopurine was shown to be in the order benzamido > acetamido > phthalimido. 9-(3-Acetamido-2,5-di-0-acetyl-3-deoxy-j8-D-ribofuranosyl)-2,6-dichloropurine has been synthesized and converted into the corresponding 2,6-diamino- and 6-amino-2-chloro(fluoro)-nucleosides. ... 

Nudeosides, Nudeotides, and their Derivatives.—Uridine, uridine 5 -(niethyl oxyacetate), 6-chloro-9-j8-D-ribofuranosylpurine, 6-methyl-9-j8-D-ribofurano-sylpurine, 5-acetyl-l-(3,5-0-isopropylidene-j8-D-xylofuranosyl)uracil, 2 -de-oxycytidine, the 1 1-complex of cytidine and iV-benzyloxycarbonylglutamic acid, l-(3-0-methyl-j8-D-arabinofuranosyl)cytosine, 2 -deoxyadenosine 5 -(sodium phosphate), 9-j8-D-arabinofuranosyladenine hydrochloride, 8-j8-D-ribofuranosyladenine, 8 - (2 - deoxy - oc - d - erythro - pentofuranosyl) - 6 -hydroxy-purine, l-methyl-4-jS-D-erythrofuranosyl-4-imida2oline-2-thione, and 4,6-di-0-acetyl-l,3 -anhydro-2,3-dideoxy-3-[3-hydroxy-5-methyl-(2if)-l,2,6-thiadiazin-2-yl l,l-dioxide]-a-D-n 6o-hexopyranose (455). ... 

A series of three papers has described the reactions of 2-acyloxyisobutyryl chlorides with nucleosides (particularly cytidine) to give 3 - and 3, 5 -acylated 2,2 -anhydro-jS-D-arabinofuranosyl-nucleosides, which can be converted into the corresponding l-/3-D-arabinofuranosyl-nucleotides with either aqueous pyridine or sodium carbonate-sodium hydrogen carbonate in aqueous /j-dioxan. 2,2 -Anhydro-5-chloro-l-(5-chloro-5-deoxy-jS-D-arabinofuranosyl)cytosine was obtained on treatment of cytidine with sulphuryl chloride in acetonitrile similarly, 1- -D-arabinofuranosylcytosinegave2,2 -anhydro-5-chloro-l-(5-chloro-5-deoxy-j3-D-... 

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