Discovery of Potent and Selective Non-Nucleotide Small Molecule Inhibitors of CD73.

CD73 is an extracellular mediator of purinergic signaling. When upregulated in the tumor microenvironment, CD73 has been implicated in the inhibition of immune function through overproduction of adenosine. Traditional efforts to inhibit CD73 have involved antibody therapy or the development of small molecules, the most potent of which mimic the acidic and ionizable structure of the enzyme's natural substrate, adenosine 5'-monophosphate (AMP).

No acid required: 4π and 6π electrocyclization reactions of dienyl diketones for the synthesis of cyclopentenones and 2H-Pyrans.

The 1,6-conjugate addition of nucleophiles to dienyl diketones produces either cyclopentenone or 2H-pyran products with high selectivity through either Nazarov (4π) or 6π electrocyclization, respectively. The outcome of the reaction is dependent upon the nature of the nucleophile used. Nucleophiles that are anionic or easily deprotonated exclusively produce cyclopentenones via Nazarov cyclization, whereas the neutral nucleophile DABCO promotes 6π cyclization to afford 2H-pyrans.