Cytidine 5 -chloro

In contrast to uridine,389 cytidine does not yield a 5 -chloro-5 -deoxy derivative on reaction with N,N-dimethyl(chlorometh-animinium) chloride instead 2,2 -anhydrocytidine is formed.395 However, thionyl chloride or bromide in hexamethylphosphor-amide at room temperature achieves this selective replacement of the primary hydroxyl group of halogen in cytidine, and also in adenosine, in respective yields of 80 and 75% for the chloro compounds, and 55 and 30% for the bromo analogs.396... 

In their first synthesis of cytidine, Todd and co-workers reacted the 0-acetylated 4-O-ethyluridine (147) (obtained via the classic Hilbert-Johnson reaction of 2,4-diethoxypyrimidine with 2,3,5-tri-O-acetyl-l-chloro-ribose) with methanolic ammonia to afford, via AE intermediate... 

The first iV-oxidation of alkoxypyrimidines was reported by Ochiai and Yamanaka, who used hydrogen peroxide-acetic acid. Cytidine iV -oxide (232) has been prepared by the oxidation of cytidine with m-chloro-peroxybenzoic acid in glacial acetic acid. The AT -oxide of cytidine 5 -phosphate has also been prepared. ... 

The earliest mechanistic studies utilizing alternate substrates were first reported in 1976 by Thelander and co-workers on the inactivation of RDPR by 2 -chloro-2 -deoxyuridine 5 -diphosphate (CIUDP) and the cytidine analog, CICDP (9). 

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. 

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-... 

At the start of this work, x-ray diffraction studies had established that the only platinum coordination sites which existed in isolable compounds prepared by reaction of chloro-platinum complexes, including PtCt2(NH3)2 with purine and pyrimidine bases were N7 for guanosine (21), Nl and N7 for adenosine (22,23), N3 for cytidine (24) and no reaction with thymidine. 

The use of A -morpholino-0,0-bis[(6-trifluoromethyl)benzotriazolyl] phosphate and 2-chloro-4iV-l,3,2-benzodioxaphosphorin-4-one as phosphoiylating and phosphitylating agents, respectively, and the activation of nucleoside 3 -phosphonates by tris(2,4,6-tribromophenoxy)dichlorophosphorane are covered in Chapter 20, as is the synthesis of cytidine diphosphate 3,6-dideoxyhexoses (synthetic nucleosides). 

Azido and 3 -amino analogues of 2 -deoxy-5-substituted uridine and cytidine, together with 3 -amino-5 -fluoro-thymidine, have been prepared by standard procedures using 3 -0-mesyl ester intermediates the most active anti-cancer compounds were the 3 -amino-5-fluoro analogues of 2 -deoxyuridine and 2 -deoxycytidine cuid the 3 -amino analogue of 2 -deoxycytidine.An alternative doubleinversion sequence at C-3 using a 3 -chloro-3 -deoxyxylo-nucleo-side intermediate has been described for the preparation of 3 -... 

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). ... 

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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