15465-98-2

Upstream product

• 108-24-7 acetic anhydride 
• 147-94-4 arabinosyl cytosine 
• 13491-47-9 N₄-acetyl-4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one 

Downstream Products

• 91146-91-7 2'-O-3'-O,N⁽⁴⁾-Triacetylarabinofuranosylcytidylyl 5'-(2',3'-di-O-isopropylidene-6-methylthiopurine riboside), 5'-(2-chlorophenyl)phosphate 
• 159505-48-3 N⁴-acetyl-1-<2',3'-di-O-acetyl-5'-(2,3,4,6,-tetra-O-acetyl-β-D-galactopyranosyl)-β-D-arabinofuranosyl>cytosine 
• 6742-08-1 N⁴,2',3',5'-O-tetra-acetylarabinosylcytosine 

Relevant academic research and scientific papers

Differential reactivity of carbohydrate hydroxyls in glycosylations. II. The likely role of intramolecular hydrogen bonding on glycosylation reactions. Galactosylation of nucleoside 5'-hydroxyls for the syntheses of novel potential anticancer agents

Contrary to expectations, many primary hydroxy groups are completely unreactive in glycosylation reactions, or give the desired glycosides in very low yields accompanied by products of many side reactions. Hydrogens of such primary hydroxyls are shown to be intramolecularly hydrogen bonded. Intermediates formed by nucleophilic attack by these hydroxyls on activated glycosylating agents may resist hydrogen abstraction. This resistance to proton loss is postulated to be the origin of the observed unreactivity. It is shown that successful glycosylations take place under acidic conditions under which such hydrogen bonds cease to exist. Accordingly, direct galactosylations of the normally unreactive 5'-hydroxyls of nucleosides were accomplished for the first time with a galactose trichloroacetimidate donor in chloroform under silver triflate promotion. It is noted that such galactosylated anticancer nucleosides may have improved biological specificity. Contrary to expectations, many primary hydroxy groups are completely unreactive in glycosylation reactions, or give the desired glycosides in very low yields accompanied by products of many side reactions. Hydrogens of such primary hydroxyls are shown to be intramolecularly hydrogen bonded. Intermediates formed by nucleophilic attack by these hydroxyls on activated glycosylating agents may resist hydrogen abstraction. This resistance to proton loss is postulated to be the origin of the observed unreactivity. It is shown that successful glycosylations take place under acidic conditions under which such hydrogen bonds cease to exist. Accordingly, direct galactosylations of the normally unreactive 5′-hydroxyls of nucleosides were accomplished for the first time with a galactose trichloroacetimidate donor in chloroform under silver triflate promotion. It is noted that such galactosylated anticancer nucleosides may have improved biological specificity.

Nucleoside conjugates. 6. Synthesis and comparison of antitumor activity of 1-β-D-arabinofuranosylcytosine conjugates of corticosteroids and selected lipophilic alcohols

Five new P1-(steroid-21-yl)-P2-(1-β-D-arabinofuranosylcytosin-5'-yl)pyrophosphat es (ara-CDP-steroids), five 1-β-D-arabinofuranosylcytosine 5'-O-(alkyl)phosphates (ara-CMP-alkyl esters), and two P1-(alkyl)-P2-(1-β-D-arabinofuranosylcytosin-5'-yl)pyrophosphate (ara-CDP-alkyl esters) have been prepared and evaluated against L1210 lymphoid leukemia in culture and in mice (C3D2F1/J). These include ara-CDP-11-deoxycorticosterone, ara-CDP-cortisone, ara-CDP-corticosterone, ara-CDP-cortexolone, and ara-CDP-prednisone, ara-CMP hexadecyl ester, ara-CMP 1-cyclohexylmethyl ester, ara-CMP 1-adamantylmethyl ester, ara-CMP 2-(1-adamanthyl)ethyl ester, ara-CMP 2-chloroethyl ester, ara-CDP hexadecyl ester, and ara-CDP 1-cyclohexylmethyl ester. The in vitro antitumor results indicated that ara-CDP-steroids were as active as the previously reported ara-CMP-steroids and that ara-CMP and ara-CDP-alkyl esters were less growth inhibiting than ara-CDP-steroids and ara-C. However, the in vivo antitumor results indicated that ara-CDP-steroids were generally less effective than the previous monophosphate derivatives. Among them ara-CDP-corticosterone and the known ara-CDP-cortisol showed greater efficacy than ara-C with ILS value of 152% and 209%, respectively, at the optimal dose of 40 and 80 (mg/kg)/day for 9 days, while that of ara-C was 138% at the optimum dose of 9.2 (mg/kg)/day. Generally, ara-CMP alkyl esters, given ip to the L1210 leukemic mice, were found to be toxic and ineffective. However, ara-CDP hexadecyl ester showed marginal activity (ILS, 38%). These preliminary results support the thesis that the ara-C conjugates of this type may require a lipophilic and naturally occurring moiety for improved efficacy.