Title: Novel Formamidinyl Pyri(mi)dinium Ylide Chemistry for ARP2/3 Complex Inhibitor Development for Naegleria fowleri
By: Dr. Siva Rasapalli, Chemistry and Biochemistry, UMass Dartmouth
The rich chemical reactivity of pyri(mi)dinium salts has been widely tapped in organic synthesis. However, the related pyri(mi)dinium ylide chemistry is still in its infancy. We proposed to employ the electrophilicity of the tethered 2-formamidinyl functionality to diversify the possible applications of pyri(mi)dinium ylides which are generally considered as nucleophilic for the synthesis of variously substituted imidazopyri(mi)dine library generation. The design of these libraries are guided by two objectives: 1. To enable the total synthesis of oroidin and its congeners for anti-bacterial and other medicinal applications 2. to generate the structural library of the mammalian actin network inhibitor CK-666 with an objective of developing specific inhibitors for Naegleria fowleri, the “brain-eating amoeba,” a devastating disease for which there is a lack of reliable treatments and a >95% case fatality rate. The details of this two-pronged research plan will be shared.
