No abstract

A set of derivatives of cyclopentaneacetic acid &-substituted at position 3 by nucleoside bases (both purines and pyrimidines) were prepared and characterized (see 11, 14, and 23a, b; Schemes 2 4 ) . These molecules are carbocyclic analogs of 2,3'-dideoxy-5'-homonucleosides. In this synthesis, the skeleton was constructed from norbornanone and a novel method based on Mitsunobu chemistry used for the introduction of nucleoside-base substituents. The scope of this method was further explored via the preparation of a cyclobutyl analog of dideoxyguanosine (see 17, Scheme 3 ) .Introduction. -Analogs of nucleosides have attracted interest as lead compounds for treating diseases where the diseased and normal states differ in the enzymes used to process nucleic acids. Viral diseases fall within this class, and several of these promise to be among the most troubling public health problems in the future. Nucleoside analogs are also important for scientific reasons; systematic variation of the structure of the building blocks of oligonucleotides should help biological chemists understand better the chemical basis for the conformational and binding properties of this remarkable class of molecules.For such small molecules, it continues to be astonishing how many different structural variations of nucleosides are possible. Focusing only on alterations in the furanose ring, themes in the chemistry of nucleoside analogs include: i) removal of heteroatomic substituents from the ring [2], ii) replacement of these substituents by other heteroatomic substituents 131, iii) opening the ring entirely [4], iv) building carbocyclic versions of the ring [5], and v) homologating the sugar ring at one or more positions [6]. The first three themes include analogs that presently are the most important antiviral compounds. The last leads to molecules that provide entry into backbone-modified oligonucleotide analogs with potential 'antisense' activity against natural oligonucleotides [7].As part of an ongoing program to expand the structural versatility of nucleosides, we needed to understand better the reactivity of nucleoside analogs combining the first, fourth, and fifth of these themes, i.e. of compounds of the general formula 1. As

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.