Pyrimidine nucleosides condensed

Azine approach. 4-Amino-5-hydroxypyrimidine condenses with acid anhydrides or esters to form the corresponding 2-substituted oxazolopyrimidine system (77CPB491). Under relatively mild reaction conditions the nucleoside 6-amino-5-hydroxyuridine will undergo cyclocondensation with formamide under the influence of polyphosphate ester to form the oxazolo-fused nucleoside (230) both protected and non-protected pyrimidine nucleosides have been used in this reaction (73CPB1327). 

Although there are a number of inefficient steps in most proposed prebiotic syntheses of ribotides, the major objection to RNA as the primogenitor of life has been the relatively small yield of ribose in the formose reaction, a simple condensation of glycoaldehyde. Muller et a/.,18 however, have discovered a variation of the formose reaction that produces a limited mix of pentose diphosphates in which the ribose forms predominate (52 14 23 11, ribose arabinose lyxose xylose). Although many critical chemical roadblocks remain (such as the extremely low yield of pyrimidine nucleosides following the condensation of ribose and free bases), this advance belies the previously held view that products of the formose reaction are necessarily so chemically diverse that they are the carbohydrate analog of petroleum. 19... 

Esterification of dialkyl phosphates is carried out with diethyl azodicarboxylate and triphenylphosphine (equation 46). This condensation is applicable to phosphorylation of pyrimidine nucleosides. The trichloromethanephosphonic acid derivative (69 equation 47) serves as a phosphorylating agent of ribonucleosides, affording the 2 - and 3 -monophosphates. ° Ethyl vinyl ether assisted the dimeric condensation of diethyl hydrogen phosphate giving tetraethyl pyrophosphate (equation 48). ... 

The first synthesis of pyrimidine nucleosides had been reported earlier [G. Hilbert and T. B. Johnson, J. Am. Chem. Soc., 62,4489 (1930)] by means of a condensation of 2,4-diethoxypyrimidine with tetra-O-acetyl-n-glucopyranosyl bromide, but the yields were poor and the scope of the reaction was limited. 

Analogues of the pyrimidine nucleosides have been extensively studied 5-Azacytidine is antileukemic and Ribavirin, an antiviral agent, is used in the treatment of lung infections in infants. Lamotrigine is used for the treatment of epilepsy. Melamine, which on condensation with formaldehyde produces the melamine resins well known in kitchen utensils, is an important industrial intermediate. 

Syntheses of nucleoside analogues by conventional condensations of sugar derivatives with bases have included 6-azacadeguomycin and some 3,4,6-trisubstituted pyrazolo[3,4-d]pyrimidine nucleosides, ... 

Previously constructed recombinant strain E. coli BM-D6 produced homologous purine nucleoside phosphorylase (PurNPase) acting (like PyrNPase) as a key catalyst transforming pyrimidine nucleosides into modified purine nucleosides via enz5miatic transglycosylation reaction [7]. PurNPase catalyzes stereoselective reaction of intermediate a-D-pentofuranose-1-phosphate (product of pyrimidine nucleoside phosphorolysis mediated by PyrNPase) condensation with purine heterocyclic base leading to formation of modified purine nucleoside. 

There have been many reports of syntheses of deoxy nucleosides by standard sugar-base condensation reactions. These include 5 -deoxy-ribo nucleosides and 5 -mono- or 5",5-di-deuterated analogues, as well as derivatives of 5-deoxy-D-xylose and 5-deoxy-D-glucose, 5-alkylated thymidine derivatives, 2 -deoxy-6-methyl-5-azacytidine and its a-anomer, the thymidine analogue 4-(2-deoxy-B-D-erythro-pento-furanosyl)-6-methyl-l,2,4-triazine 3(HH)-one-1-oxide, 6-aza-3-deaza analogues of 2 -deoxy-cytidine and 2 -deoxyuridine,3 -deoxycytidine from a 3-deoxy-ribofuranose obtained from a fermentation broth producing the 3 -deoxy nucleoside antibiotic, cordycepin, 4-deoxy-DL-threo-pentopyranosyl pyrimidine nucleosides, and 5 -C-methyluridines derived from 6-deoxy-D-allose and 6-deoxy-D-talose. A range... 

Deoxy-l, 2 5,6-di- O-isopropylidene-3- C-methylene-a-D-ri2>o-hexofuranose has been converted in several steps to the branched-chain compound 18 as a precursor to 2, 3 -dideoxy-3, 4 -dihydroxymethyl pyrimidine nucleosides. The hydroxymethyl group at C-4 was introduced by way of a crossed aldol condensation of a 5-formyl derivative with formaldehyde followed by a Cannizaro reduction of the intermediate hydroxy aldehyde in a similar manner to that previously described in Vol. 13, p. 126, ref. 16. ... 

Many 5-alkyl-, 5-alkenyl-, and 5-alkynyl-l-(2-deoxy-2-fluoro- 5-D-arabin-ofuranosyl)pyrimidines (750 - 752 and 765 - 767) were prepared - " by condensation of 742 (or the equivalent, such as 743) with C-5-substituted pyrimidine derivatives, or by attachment of a C-fragment to C-5 of the existing nucleosides through their 5-iodo or 5-chloromercuri derivatives, or by further conversion of the attached C-5 substituent into another one. ... 

Condensation of D-glucono-1,5-lactone with 4 5-diamino-6-diethyla-mino-2-methylpyrimidine afforded the 8-polyhydroxyalkylpurine 101, a C-nucleoside of an open-chain sugar (118). Some other pyrimidines gave analogous products from either D-glucono- or D-ribono-lactones. 

Townsend and coworkers (80JCS(P1)1853) prepared several ribofuranosyl nucleosides of the thieno[2,3-d]pyrimidine ring system by condensation of the silylated base with l-O-acetyl-2,3,5-tri-0-benzoyl-j3-D-ribofuranose in 1,2-dichloroethane in the presence of tin(IV) chloride (Scheme 101). These nucleosides are analogs of cytidine. Uridine analogs have been prepared from thieno[2,3-rf]pyrimidine-2,4-diones. 

Aside from the successful synthesis of cytidine,185 attempts made thus far to apply the Hilbert reaction to the preparation of 1 -glycofuranosyl-pyrimidines have yielded anomalous results. Although the syntheses of 5 -methyluridine (I, R = CH3) and 5 -methylcytidine (II, R = CH3) by the condensation of sirupy tri-O-acetyl-D-ribofuranosyl bromide with 2,4-diethoxypyrimidine have been reported,192 the properties of these nucleosides differ from those of the verified substances synthesized by other routes.68 62 Other aspects of the Hilbert-Johnson procedure are discussed below. 

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