Michael Additions of Organozincates to Nitrostyrenes and Coumarins for the Obtainment of New Chelating Agents Potentially Useful in Alzheimer’s Disease Treatment

Recently, several studies have highlighted how the alteration in the homeostasis of bio-metals (e.g., copper, iron, zinc), which accumulate in the brain, may be associated with neurodegenerative diseases. One of the therapeutic options is to use bio-metal chelators able to reduce their excess in the blood stream thanks to coordination (1). Thus, the development of synthetic strategies for the preparation of effective new chelators capable of crossing the blood-brain-barrier is mandatory. This presentation, will deal with Michael additions to coumarin derivatives (Scheme 1a) and nitrostyrenes (Scheme 1b) as a means for the synthesis of new chelating agents using lithium zincate reagents (2) that despite the fact they have been known for a long time, their application in organic synthesis remain scarce. Being the compatibility of organolithium reagents with electron-poor systems very limited (3), lithium zincates species have become today very promising nucleophilic alternatives to overcome this flaw. The “effect of solvent” on the outcome of the reaction will be discussed as well. (1) R. J. Ward, D. T. Dexter, R. R. Crichton, Current Medicinal Chemistry, 2012, 19 (17), 2012. (2) D. R. Armstrong, C. Dougan, D. V. Graham, E. Hevia and A. R. Kennedy, Organometallics, 2008, 27, 6063–6070. (3) P. Vitale, V. Capriati, S. Florio, F. M. Perna, A. Salomone, Current Organic Chemistry, 2016, 21 (3), 2017.