Cytidine, 5 -phosphate, preparation

The derivative (9) of 3,6-dideoxy-a-D-xyIo-hexopyranose (abequose) was isolated from a strain of Salmonella typhimurium,16 that (10) of 3,6-dideoxy-a-D-nfco-hexopyranose (paratose) from Salmonella paratyphi,54 and a mixture of 10 and the ester (11) of 3,6-dideoxy-a-D-arabino-hexopyranose (tyvelose) from Salmonella enteritidis.,6 It was shown that these derivatives are formed from cytidine 5 -(a-D-glu-copyranosyl pyrophosphate) by treatment with nicotinamide adenine dinucleotide (NAD+) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) in the presence of cell extracts of the respective bacterial strain. For example, formation of 9 is characteristic of preparations from Salmonella, group B,55,56 or Pasteurella pseudotuberculosis, type II.56 The derivative 10 was obtained with extracts of Salmonella, group A,56 and Pasteurella pseudotuberculosis, type I and III,56 and a mixture of 10 and 11 with those of Salmonella, group D,55-60 or Pasteurella pseudotuberculosis, type IV 56.59,60 Under similar conditions, the ester (12) of cytidine 5 -pyro-... 

The N-acetylneuraminic acid derivative 44 is widely distributed. It was isolated from a strain182 of Escherichia coli, and has been obtained from cytidine 5 -triphosphate and N-acetylneuraminic acid by the action of enzyme preparations from Neisseria meningitidis183 and from animal tissues.184-186 The latter enzyme can also make use of N-glycolylneuraminic acid as a substrate, to give the respective cytidine 5 -phosphate derivative. 

Some of the reactions of PO3- parallel enzymatic reactions promoted by adenosine triphosphate (ATP). Pyruvate kinase catalyzes the equilibration of ATP and pyruvate with adenosine diphosphate (ADP) and phosphoenol pyruvate (11,12). In a formal sense, this reaction resembles the preparations of enol phosphate (eqs. 6 and 7). Cytidine triphosphate synthetase catalyzes the reaction of uridine triphosphate with ammonia to yield cytidine triphosphate (13). In a formal sense, this reaction resembles the replacement of the ester carbonyl group of ethyl acetate by the nitrogen of aniline (eq. 8). 

Synthetic cytidine ribitol pyrophosphate was prepared by condensing cytidine 5-phosphate and D-ribose 5-phosphate in the presence of dicyclohexylcarbodiimide, followed by the reduction of the cytidine D-ribose pyrophosphate with sodium borohydride. 

Extracts prepared from whole cells of all such organisms contained a glyceritol phosphate polymer, even when no such polymer was present in the walls. This finding is in accordance with a previous report by Mitchell and Moyle that the cell envelope and the small particle fraction from Staphylococcus aureus contain a glyceritol phosphate. This observation could explain why Lactobacillus arabinosus contains cytidine glyceritol pyrophosphate (and not the corresponding teichoic acid) in the cell wall. 

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. ... 

Szabo and his colleagues have prepared 3-deoxy-D-crj f/iro- and U-threo-hcx-2-ulosonic acid 5-phosphate in the ratio 2 1 as illustrated in Scheme 1. The products were isolated in 37 and 23% yield, respectively, as their magnesium salts.In parallel fashion, Russian workers have developed a synthesis of 3-deoxyaldulosonic acids as depicted in Scheme Studies by n.m.r. spectroscopy of ot- and /3-A-acetylneuraminic acid derivatives and determination of /c-i-H-3 e values allowed the conclusion that, in cytidine 5-phospho-iV-acetyl-neuraminic acid, a key intermediate in the biosynthesis of glyconoconjugates, the neuraminic acid moiety has the 3-configuration. ... 

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-... 

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