Boranophosphate oligonucleotides

Boranophosphate linkages have been of interest because they mimic natural DNA, and may have potential in diagnostic and therapeutic applications (boron neutron capture therapy). Boranophosphate-modified siRNA has been shown to possess potent gene-silencing properties compared to the unmodified siRNA. Two novel methods have been reported for the synthesis of boranophosphate oligonucleotides, one using phosphoramidite chemistry, the other boranophosphotriester chemistry. Dinucleoside boranophosphates and a-borano nucleoside triphosphates have also been described. " ... 

Figure 1.2 Modified nucleotides and nucleosides described in the text. (A) Nucleotides incorporated by polymerases yielding nuclease-resistant oligonucleotides. Top from left to right 2 -fluoro, 2 -amino, 2 -0-methyl. Bottom from left to right boranophosphate, phosphorothioate, 4 -thio. (B) Photosensitive residues. Left to right 5-bromo-U, 2-(2-nitrophenyl)ethyl T, 2-(2-nitrophenyl)propyl T. (C) Amino-imino equilibrium used in 2D-SELEX (see the text).

A previously-reported bicyclic 3 -aminonucleoside has now been converted to the dinucleotide building block 225, which caused a reduction in values when incorporated into oligonucleotides. There has been an extended and expanded account of the preparation of dideoxynucleoside boranophosphates through the intermediacy of H-phosphonate diesters. The conversion of these to the boranophosphates proceeds with retention of configuration. ... 

Reaction of dimer 1 with 5 -DMT-thymidine phosphoramidite, followed by Me2S BH3, results in the formation of trimer 3 (trinucleoside boranophosphate methylester, 3) (see Scheme I) in which both intemu-cleotide linkages are boranophosphate methyl ester groups. This reaction was carried out with equal molar amounts of 1 and DMT-thymidine-phosphoramidite, and the yield of 3 was only 22.4% prior to and 5.2% after HPLC. Yet a large proportion (ca. 66%) of dimer 1 was recovered unreacted. Clearly, the procedure must be optimized to obtain a 99%+ coupling yield before it could be used for practical synthesis of oligonucleotides. In a second experiment performed in an NMR tube, 5 Eq of amidite resulted in >95% conversion. 

Studies Toward the Development of a Solid-Phase Method for the Synthesis of Oligonucleotide Boranophosphates... 

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