In comparison to P (III) compounds the activation of phosphate P (V) compounds towards nucleophillic substitution is unfavorable due to the presence of the phosphoryl oxygen in place of a lone pair of electrons. We have previously reported that boranephosphonates reduce metals ions such as Au (III), Ag (I) and Pt (II) to produce the corresponding metallic nanoparticles. 1, 2The boranephosphonate itself was converted to the phosphodiester or phosphotriester when the reaction was carried out in water or alcohols respectively. Thus even though boranephosphonates posses stability similar to phosphates this reaction provides an avenue for their activation towards nucleophillic substitution reactions. This therefore led to us investigate whether a similar reaction also occurs in the presence of other oxidizing agents that are better suited for organic transformations.Here we show that boranephosphonate diesters undergo nucleophillic substitution by different nucleophiles (amines, alcohols, thiols and Grignard's reagents) upon activation by iodine, to yield phosphoramidates, phosphotriesters, phosphorothioates and alkylphosphonates respectively. The reaction proceeds quantitatively both in solution as well as on solid-support bound oligonucleotides. We show that a variety of modifications such as fluorophores, azides and phosphotriesters that are sensitive to the conditions of DNA synthesis can be introduced in a post-synthetic manner using this reaction. Furthermore, investigations of the reaction have revealed that the substitution at the phosphorous occurs in a stereospecific manner through the formation of an iodophosphate intermediate. Beyond oligonucleotide synthesis these results are relevant towards the synthesis of other stereo-defined phosphate containing molecules such as phosphate linked disaccharides which are being investigated as potential therapeutics.    References:   1. Roy, S.; Olesiak, M.; Shang, S. and Caruthers, M. H. J. Am. Chem. Soc. 2013 , 135, 6234 � 6241. 2. Roy, S.; Olesiak, M.; Padar, P.; McCuen, H. and Caruthers, M. H. Org. Biomol. Chem., 2012 , 10, 9130�9133

Boranephosphonate DNA: Intermediates in the synthesis of internucleotide phosphate analogs

248th National Meeting (2014)

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