Synthesis and Biochemical Activity of New Oligonucleotide Analogs

Borane phosphonate deoxyoligonucleotides are synthesized from 5′-O-benzhydroxybis(trimethylsilyloxy)silyl-2′-deoxynucleoside-3′-phosphoramidites. The exocyclic amines of adenine and cytosine are protected with dimethoxytrityl and trimethoxytrityl, respectively, whereas guanine protection is with N2-(9-fluorenylmethoxycarbonyl) or N2-trimethoxytrityl. Thymine is protected with N3-anisoyl. Using these synthons and under standard conditions via activation with tetrazole, condensations in excess of 99% are observed. Oxidation with either THF·BH3 or a peroxyanion solution followed by cleavage of the silyl ether with fluoride completes a cycle. Following synthesis of an appropriate oligomer, protecting groups are removed using sequentially acetic acid, a dithiolate and ammonium hydroxide. Oligodeoxynucleotide 10 mers and 12 mers having any combination of borane phosphonate and phosphate internucleotide linkages as well as all four 2′-deoxynucleotides are synthesized in isolated yields of 70–80% and characterize...