Stereocontrolled Synthesis of Highly Substituted trans α,β-Unsaturated Ketones with Potent Anticancer Properties from Glycals

A novel synthetic route for highly substituted conjugated ketones has been developed utilizing glycals as starting materials. The two-step process combined the Heck reaction/Lewis acid promoted ring opening to afford the products in 33-80 % overall yields and with a high level of trans stereoselectivity. Since the products are essentially the aldols, this methodology may be employed in some cases as an alternative synthetic route to the typical aldol condensation. Densely substituted, selectively protected conjugated ketones are synthetically attractive structures which, in our case, proved to be biologically equally appealing. Namely, they showed activity against several cancer cell lines, such as HeLa, K562, MDA-MB-453, in some instances overperforming cisplatin used as a standard.