Abstract by Peter Mpaata
Chemistry and Biochemistry
Double Activation Intramolecular Styryl Diels Alder Reaction: A strategy for synthesis of anticancer agent deoxypodophyllotoxin
Total synthesis of complex polycyclic organic molecules often involves multiple steps that lower their yields. Intramolecular cycloadditions such as [4+2] are widely used to construct polycyclic cores of complex molecules. However, the use of Intramolecular styryl Diels Alder (ISDA) reaction to synthesize complex molecules is still limited. The use of ISDA reaction was demonstrated in our lab by accomplishing a 7-step synthesis of potent anticancer deoxypodophyllotoxin.This breakthrough has inspired the development of asymmetric ISDA reaction using chiral substrates. This new approach would involve double activation with two conjugated carbonyl groups to the dienophile and two-point binding with mild Lewis acids to favor high reactivity and stereoselectivity. Substrates for ISDA will be synthesized from cinnamyl alcohol, propynoic acid and chiral auxiliary obtained from L-phenylalanine. Reactivity will be explored with thermal and Lewis acid activation (Cu(OTf)2, MgBr2.OEt2, ZnCl2 and Fe(II) at reduced temperature. Synthesis of the tricyclic core for anti-cancer deoxypodophyllotoxin will be synthesized using this method.