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A novel 2′-modification, 2′-O-[3-(N,N-dimethylamino)propyl] or 2′-O-DMAP, has been incorporated into oligonucleotides and compared to the known 2′-O-(3-aminopropyl) or 2′-O-AP modification for antisense properties. The 2′-O-DMAP modified oligonucleotides exhibit very high nuclease resistance like the 2′-O-AP modification due to the ‘charge effect’ and maintain high binding affinity to target RNA relative to known modifications when a few 2′-O-DMAP residues are dispersed throughout the oligonucleotide.

The alkylation of N -3-benzyloxymethyl-5-methyluridine with 1,3,2-dioxathiolane 2,2-dioxide or 1,3,2-dioxathiane 2,2-dioxide resulted in a 2′- O versus 3′- O selectivity of 3:1, respectively. The resulting product has a built-in sulfate leaving group at the terminal end of an ethyl or propyl carbon chain, which can be displaced with sulfur and nitrogen nucleophiles to produce modifications at the 2′- O or 3′- O positions.

The novel RNA mimic 2′-O-AOE has been incorporated into antisense oligonucleotides. This 2′-O-modification significantly enhances hybridization against target RNA, and furthermore, exhibits specificity for RNA over DNA. The nuclease resistance (SVPD) of 2′-O-AOE modified phosphodiester oligonucleotides is significantly higher than the unmodified DNA and comparable to the 2′-O-MOE oligonucleotides.

Studies on an unexpected reaction involving a reductive cleavage of the pyridazine moiety of a tricyclic heterocycle are described. Structure assignments for the products obtained from the reductive cleavage were made using physicochemical methods.

A total synthesis of 2-amino-7-(O-D-ribofuranosyl)pyrrolo(2,3-dlpyrimidin-4-one- properties. We now wish to report a total synthesis of the nucleoside 2-amino-7-(B-D-ribo- furanosyl)pyrrolo(2,3-dlpyrimidin-4-one-5-carboxylic acid (2, cadeguomycin). We initiated two separate routes for the total synthesis of cadeguomycin, with each route being designed to ultimately afford the desired antibiotic. In the first route investigated, we envisaged the use of 2-amino-7-(O-D-ribofuranosyl)pyrrolo(2,3-dl-pyrimidin-4-one-5- - carboxamide (4) as the immediate precursor of cadeguomycin. The synthesis of this precursor (4-j was accomplished from the nucleoside antibiotic toyocamycin via a seven step sequence. - However, the low yield (14%) from the last step, treatment of 2-amino-5-cyano-7-(&D- ribofuranosyl)pyrrolo(2,3-dl-pyrimidin-l-one 8