Pyrimidines ribosyl

The first chemical synthesis of these substances, using a procedure which yields 1-ribofuranosyl derivatives by pyrimidine bases, was described by Hall. By using the mercuric salt of 6-azathymine and tribenzoate of D-ribofuranosyl chloride, he obtained a mixture of two monoribosyl derivatives and a diribosyl derivative. He determined the structure of the 3-substituted derivative by the similarity of spectra and other properties to those of 3-methyl-6-razauracil. The structure of the 1-ribosyl derivative was then determined from the similarity of the spectra with 6-azathymine deoxyriboside obtained enzymatically. 

P2J2A Z = 8 Dx = 1.931 R = 0.034 for 2,321 intensities. There are two molecules in the asymmetry unit, and both exhibit the syn disposition (—84.5°, + 76.1°) for the base. The conformation of the D-ribosyl group is 3T4 (28.5°, 39.4°) in molecule A and 3T2 (359.9°, 36.2°) in molecule B. The exocyclic, C-4 -C-5 bond torsion-angle is gauche+ for both molecules (55.2°, 59.7°). The purine bases of the crystallograph-ically independent molecules are paired by N-l-H 0-6 hydrogen bonds across a pseudo-two-fold axis. The bases are stacked such that the Br atoms are tucked under the pyrimidine moiety of the adjacent... 

Figure 20.9 The positions in the pathway for de novo pyrimidine nucleotide synthesis where GLUCOSE provides the ribose molecule and GLUTAMINE provides nitrogen atoms. Glucose forms ribose 5-phosphate, via the pentose phosphate pathway (see chapter 6), which enters the pathway, after phosphorylation, as 5-phospho-ribosyl 1-pyrophosphate. Glutamine provides the nitrogen atom to synthesise carbamoylphos-phate (with formation of glutamate), and also to form cytidine triphosphate (CTP) from uridine triphosphate (UTP), catalysed by the enzyme CTP synthetase. It is the amide nitrogen of glutamine that is the nitrogen atom that is provided in these reactions.

The formation of the adduct between 86 and the nitrile, i.e., 89, occurs more readily than that between 86 and ketones, since an activated nitrile is a better nucleophile than a ketone. Since the ce-proton in the adduct 89 is more acidic than the ce-proton in the ketonic adduct, also the ring opening will occur more easily. The interchange of a nitrile carbon with the ring carbon of a pyrimidine ring was also observed with the 3-benzyloxymethyl-l-ribosyl-5-cyanouracil. With a series of activated nitriles, the protected bi-cyclic nucleosides are formed. After deprotection, the corresponding bi-cyclic nucleosides are obtained (Scheme IV.35). 

Scheme 4 Biosynthesis of pyrimidine nucleotides (P = P03H2, PP = P206H3) (11a) ribosyl-5- ...

The photoaddition of water to a variety of naturally occurring pyrimidine derivatives has been reported. Photolysis in aqueous solution of uracil (224 R = H), uridine (224 R=ribosyl), and uridylic acid results in the formation of the corresponding 6-hydroxy-5,6-dihydropyrimidine (225)208-210 these structures have been established by independent synthesis.209 Analogous photoadditions have been observed in 1,3-dimethyluracil211 and 5-fluorouracil.212 These additions are reversible. 

Elementary analyses indicated that the sugar moieties of pyrimidine nucleosides derived from deoxyribonucleic acid are also of the deoxypen-tosyl type. Early attempts to apply the hydrogenation procedure of Levene and LaForge60 were unsuccessful. It was generally assumed, however, that the sugar portion of the pyrimidine nucleosides of deoxyribonucleic acid is probably also of the 2-deoxy-D-ribosyl type. 

From indirect chemical evidence, Levene and his collaborators assigned the Nl position as the point of attachment of the d-ribosyl moiety to the pyrimidine ring. Those reactions have been described by Tipson10 and are presented in summary form in Table I. 

Chemical Evidence which Established N1 as the Position of Attachment of the Ribosyl Moiety to the Pyrimidine Ring... 

---