Abstract: Oligonucleotide analogs are disclosed having pyrimidine monomeric sub-units therein that are modified at the 2? and 5? positions. Monomeric sub-units having these modifications may be further modified at the 2? position. Improved processes for the synthesis of 2?-O-substituted pyrimidine nucleosides are also provided. The processes feature alkylation of a 2,2?-anhydropyrimidine nucleoside or a 2S,2?-anhydropyrimidine nucleoside with a weak nucleophile in the presence of a Lewis acid.

Abstract: Oligonucleotide analogs are disclosed having pyrimidine monomeric sub-units therein that are modified at eh 2? and 5? positions. Monomeric sub-units having these modifications may be further modified at the 2? position. Improved processes for the synthesis of 2?-O-substituted pyrimidine nucleosides are also provided. The processes feature alkylation of a 2,2?-anhydropyrimidine nucleoside or a 2S,2?-anhydropyrimidine nucleoside with a weak nucleophile in the presence of a Lewis acid.

Abstract: A process for production of the two or more molecules of interest. The present process may be advantageously used to produce two, three, four or more molecules of interest (the same or different from one another) on a single support material. A preferred embodiment comprises use of the present process to produce two or more oligonucleotides of interest. The process can be readily extended to other applications such combinatorial chemistry, peptide synthesis and the like. Various novel intermediates in the process are also disclosed.

Abstract: The present invention relates to improved methods for the preparation of nucleoside phosphoramidites and oligonucleotides. In one aspect, the methods of the invention are used to prepare phosphitylating reagents using pyridinium salts as activators. In a further aspect, the methods of the invention are used to prepare internucleoside linkages using activators which include at least one pyridinium salt and at least one substituted imidazole. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having 2′-substituents using imidazolium or benzimidazolium salts as an activator. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having bioreversible protecting group that confers enhanced chemical and biophysical properties, without exocyclic amine protection, using imidazolium or benzimidazolium salts as an activator.

Abstract: Oligonucleotide-mimicking macromolecules that have improved nuclease resistance are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligonucleotides with four atom linking groups provide unique compounds that are useful in regulating RNA expression and in therapeutics. Methods of synthesis and use also are disclosed.