Cytosine nucleosides, preparation

The borohydride reduction of 2 - and 3 -ketocytidine derivatives having or lacking an N4-acetyl group provided a facile route to cytosine nucleosides labeled with tritium at specific positions of the sugar.28 Reduction of either 20a or 20c with sodium borohydride in ethanol-benzene afforded the arabino and the ribo derivatives in the ratio of 4 1. Treatment of the reduction mixture with methanolic ammonium hydroxide gave the deacetylation products, 82b and 19b, isolated in crystalline form by preparative, thin-layer chromatography. 

The 2- and 3-deoxy-D-er> f/i/-o-pentosyl derivatives of 4-amino-5-ethoxy-carbonylimidazole (45) have been prepared from the corresponding ribofuranosyl derivative via l - and 3 -chloro-nucleosides prepared by treatment with O-acetyl-salicyloyl chloride. Scheme 8 shows the reaction of cytosine with thionyl chloride giving 5 -chloro-5 -deoxy-ribo- and -arabino-analogues, which were then... 

The conversion of cytosine nucleosides to DNA thymidylate has been demonstrated repeatedly since the original work of Reichard and Estbom (21). Maley and Maley (22) showed that labeled deoxycytidylate was converted to DNA thymidylate in a DNA-synthesizing system prepared from chick embryo and, thus, the existence of a deoxycytidylate deaminase was indicated. This enzyme, which is described below, and the cytidine-deoxycytidine deaminase activity are the only deaminases for cytosine derivatives known to occur in animal cells. 

To prepare the corresponding cytosine containing nucleoamino acid 9, N -Boc cytosine was first silylated using N,0-bis(trimethylsilyl)acetamide (BSA) under carefully controlled conditions to produce mono-silylated-N -Boc cytosine 7. The mono-silylated product 7 undergoes l2-mediated nucleosidation with the O-MTM... 

Because synthesis of l-(2-deoxy-2-fluoro-)S-D-arabinofuranosyl)cytosine (744, FAC), an elementary arabino type of nucleoside having a growth-inhibitory effect against L 1210 leukemia in mice, through direct introduction of a fluorine atom in the 2 - up (arabino) position was difficult, compound 744 was prepared by condensation of trimethylsilylated A -acetylcytosine with 3-0-acetyl-5-(7-benzoyl-2-deoxy-2-fluoro-D-arabin-ofuranosyl bromide (742), which had been prepared by periodate oxidation of 6-0-benzoyl-3-deoxy-3-fluoro-D-glucofuranose (741). Similar condensa-... 

David and Lubineau191 reported the synthesis of pseudocytidine [5-/3-D-ribofuranosylcytosine (270)] and its a anomer by a procedure analogous to that used in preparing pseudouridine.155-157 Thus, 2,4 3,5-di-O-benzylidene-a/de/iydo-D-ribose (223) was condensed with the dilithio derivative of 2-0,4-N-(trimethylsilyl)cytosine, and the resulting, epimeric, acyclic derivatives were subjected to acid-catalyzed cyclization. The anomeric configuration of the free C-nucleosides was ascertained by spectroscopic methods and by their transformation into a- and /3-pseudouridine in the presence of nitrous acid. The anomeric 5-(/3-D-ribofuranosyl)isocytosines have also been prepared by Fox and coworkers.1913... 

Nucleosides Derived from Fluorinated Bases Many nucleosides have been synthesized from different fluoropyrimidines (uracil, thymidine, cytosine) or fluoropurine (adenine, guanine) bases, which are generally prepared by electro-... 

Regioselective ring-cleavage of cyclic derivatives of carbohydrates is a useful method for achieving their selective deprotection. 3, 5 -0-(Tetraisopropyldisiloxane-l,3-diyl) derivatives of nucleosides (51, B = uracil-1-yl, cytosin-l-yl, N4-benzoylcytosin-l-yl, guanin-9-yl, or adenin-9-yl) have been prepared,317 and selectively cleaved in 95% yield at the silicon-0-3 bond on treatment with 0.2 M sodium hy-... 

Glycosylation of N-heterocycles. A few years ago Niedballa and Vorbriiggen4 reported that pyrimidine nucleosides can be prepared by reaction of 2,4-trimethylsilyl derivatives of uracils or cytosines with 1-alkoxy or 1-acyloxy derivatives of protected sugars in the presence of Friedel-Crafts catalysts, particularly SnCl4 (equation I). 

BSA was effective for the derivatization of purine and pyrimidine bases [456] and nucleosides [457]. Bases were silylated by heating at 150°C with BSA—acetonitrile (1 3) for 45 min. It was stated that under these conditions the TMS derivative of guanine can be prepared reproducibly, but both cytosine and 5-methylcytosine provided two peaks. Silylation of nucleosides, including pseudouridine, was carried out by heating at 120°C with a 100-fold excess of BSA for 2 h. With the use of OV-17 as the stationary phase, this procedure was adopted for the determination of the composition of ribonucleic acids. 

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