Journal of Undergraduate Chemistry Research
Coumarin is a natural product found in many plants. Recently, simple coumarin analogues containing an α-methylene functional group have been synthesized and shown to exhibit cytotoxicity against cancer cell lines. The α,β-unsaturated carbonyl found in these analogues is thought to be responsible for their bioactivity. Other natural products containing this functional group have been shown to react with intracellular thiols causing tumor growth suppression. Using these analogues as a template, two new compounds have been designed that feature a novel α-methylene indanone structural framework. Since ketones are better electrophiles that esters, it is hypothesized that these analogues will react more rapidly with thiols that their coumarin counterparts. The two α-methylene indanone analogues, one incorporating an isopropyl and the other an n-butyl substituent, have been prepared in five and seven steps respectively. Both synthetic sequences feature a 1,4-organometallic addition reaction, in intramolecular Friedel-Crafts acylation, and an α-methylenation of the key inadone intermediates.
Mechelke, Mark F.; Hopfner, Sarah; McIntire, Natalie; and Cherry, Nathanial, "Chemotherapeutic Agents from Natural Product Templates: The Design and Synthesis of Novel Indanone Analogues" (2016). Chemistry Faculty Publications. 9.