Phosphorylation:

Phosphates are a ubiquitous functional group within biological systems that are incorporated in critical molecules such as DNA, RNA, proteins and small molecule messengers such as ATP and inositol phosphates.  The development of new and more efficient methods for forming phosphorylated compounds can impact the treatment of diseases where phosphorylation is aberrant (such as cancer), initiate the use of phosphorylated small molecules in disease treatment and answer fundamental questions about the nature of this chemical structure.

Research in my group focuses on the development of new methods to phosphorylate alcohols utilizing both phosphorous (III) and phosphorous (V) reagents. Current limitations in these reactions include non-catalyzed pathways, poor protecting groups on phosphorous and harsh reaction conditions.

Phosphorous (III):

Typically, phosphorous (III) reactions require an excess of tetrazole (the catalyst). This is most likely the result of deactivation of the catalyst from the amine by-product formed during the reaction. We hypothesized that addition of amine scavengers should sequester the by-product and allow the catalyst to regenerate.

We have succesfully demonstrated that addition of isocyante additives faciliates efficient turnover of the tetrazole catalyst. This process was validated with primary, secondary and tertiary alcohols as well as a variety of phosphoramidites (see: P.B. Brady, E.M. Morris, O.S. Fenton and B.R. Sculimbrene Tetrahedron Lett. 2009, 50, 975-978.)