Pyrimidine nucleoside transformations via anhydronucleosides.

The field of nucleosides has undergone rapid growth and development during the past decade'—3. Whereas, earlier studies were concerned with the development of methods for the synthesis of the nucleoside components of the nucleic acids, today several methods are available—each of which has its advantages and limitations. The host of "fraudulent" or "anomalous" nucleosides available today attests to the ability of chemists to cope with this interesting and rather complex group of compounds. Nor have their efforts been unrewarding. It is obvious to all that nucleosides have provided their fair share of interesting biochemicals useful in the elucidation of biosynthetic pathways and helpful both as anti-neoplastic and anti-viral agents. In addition, the increasing amount of "odd" nucleosides found as minor components of certain nucleic acids4, especially of transfer RNA, has further stimulated chemical efforts in this area. Finally, the continuing discovery of nucleoside antibiotics5 (of which there are now over twenty) has served to introduce an increasing number of natural-products chemists into this burgeoning field. This discussion deals with but one aspect of our research during the past few years in the area of the pyrimidine nucleosides and is not intended as a comprehensive review. Specifically, it covers that aspect of our endeavours involved in the use of preformed nucleosides, natural or anomalous, as precursors for the synthesis of new nucleosides. As with most workers in this area, our studies are motivated by biochemical or biological interests, and reference to such considerations will be made in this discussion. Nucleoside chemistry is replete with examples from many laboratories of nucleoside transformations which involved alteration only of the aglycon portion, that is, reactions in which the sugar moiety played a "passive" role. Halogenation, methylation, thiation, deamination, etc. of the main nucleosides of the nucleic acids (Figure 1) and of others are well documented'—3. Our main interest however was in alterations in the carbohydrate moieties of nucleosides. One of the significant developments in nucleoside chemistry was the earlier discoveries6 by Brown, Michelson, Todd and their associates at Cambridge who showed that pyrimidine anhydronucleosides (or "cyclonucleosides") could be formed which involve an oxygen bridge between carbon-2 of the aglycon and the sugar moiety. We will discuss the chemistry of these and other types of anhydronucleosides as tools for stereochemically-controlled reactions involving: