The Synthesis of Nucleosides

Abstract

The most important developments in nucleoside synthesis in the last few years have been the application of the mercury salt procedure to both purines and pyrimidines, and the isolation of relatively stable, crystalline 2-deoxyribofuranosyl halides; as a result, almost any nucleoside may now be synthesized. Earlier syntheses, based on older methods or on the conversion of one nucleoside to another, played an essentialpart in establishing the structure of the nucleosides (and hence of the nucleic acids).

Reactions of Transglycosylation in the Nucleoside Chemistry

“…In the second step, the O-glycoside (18) undergoes transglycosylation to the N 1 -nucleoside (19), a thermodynamic product of glycosylation. Stability of the pyrimidine O-glycosides and the influence of catalysts, solvents, substituents, size of the sugar ring, etc., on the O N migration have been studied in detail [1][2][3][21][22][23][24][25][26][27] and are reviewed by Fox, Hollenberg and Watanabe [6]. Most importantly, the isomerization proceeds via the 1,O 2 -bisribofuranosyl intermediate (20), and compounds of this type have been isolated from reaction mixtures and fully characterized [28,29].…”

“…uracil, thymine, cytosine) in the chloromercury method [1][2][3]. The mechanism of the O-riboside formation has been proposed by Fox, Hollenberg and Watanabe [6], and is presented in Scheme 5.…”

“…Therefore, an alternative position (N2) is ribosylated first. This results in the formation of the kinetic product (2), which then undergoes an intermolecular rearrangement (transglycosylation) to regain the most stable aromatic system of the indazole portion. Thus, a second ribosylation at N1 gives the 1,2-bis-ribosyl intermediate (8), which decomposes to the stable final product, 1-regioisomer (3), with liberation of the 1,2-acyloxonium cation (7).…”

“…The first examples of transglycosylation reactions in the pyrimidine [1][2][3] and purine [4,5] nucleoside series were given in the early 1960 th . All those observations have been done by a careful monitoring of the composition of reaction mixtures during chemical glycosylation of heterocyclic bases and, indeed, the transglycosylation reaction is a common step in the acid-catalyzed synthesis of nucleosides.…”

Nucleoside Studies. IV.1 The Synthesis of 2',5'-Dideoxycytidines and Other Derivatives of 2'-Deoxycytidine

“…5-Iodo-2'-deoxyuridine has marked antiviral activity2-6; 5-fluoro-2'-deoxyuridine and 5-fluoro-2'-deoxycytidine are potentially useful antitumor agents.7 •8 These discoveries have led to the preparation of many analogs of the naturally occurring compounds by total and partial synthesis. 9 Total synthesis of pyrimidine deoxyribosides is feasible by the direct coupling of a deoxyribosyl halide with the mercury salt of the appropriate pyrimidine,10 but this method has limitations11 since the mercury salts are often insoluble or unreactive. Partial synthesis9 has been used to modify the carbohydrate moiety of thymidine,12 and some derivatives of 2'-deoxyuridine have recently been described.…”