Organic & Biomolecular Chemistry 2009-11-07

Expanding the borononucleotide family: synthesis of borono-analogues of dCMP, dGMP and dAMP.

Anthony R Martin, Kishor Mohanan, Delphine Luvino, Nicolas Floquet, Carine Baraguey, Michael Smietana, Jean-Jacques Vasseur

Index: Org. Biomol. Chem. 7(21) , 4369-77, (2009)

Full Text: HTML

Abstract

We previously reported the synthesis of a borononucleotide analogue of thymidine monophosphate and its association towards the formation of a new borono-linked dinucleotide. Here we describe the completion of the set of four 2'-deoxyborononucleotide analogues of natural nucleotide monophosphates, namely the previously unknown dCbn, dGbn and dAbn. These analogues were all prepared from the respective 5'-aldehydic nucleosides through a homologation/reduction sequence. The borononucleotides were subsequently obtained by either borylation (dCbn and dGbn) or cross-metathesis (CM) in the presence of the Hoveyda-Grubbs catalyst (dAbn). The reversible formation of the corresponding dinucleotides between these new analogues and uridine was studied by (1)H NMR, and semi-empirical calculations were carried out to provide bond length and electrostatic information that assess the structural similarities existing between these bioisosteres and their natural counterparts.