Thesis Defense: Alexandria Palazzo

Please join Yale Chemistry for a thesis seminar with Alexandria Palazzo, Herzon Group.

Title: Oxidative Dimerization Approaches Toward (–)-Lomaiviticin A

Summary: This thesis herein describes our work towards the total synthesis of (–)-lomaiviticin A. The lomaiviticins are a class of complex dimeric bacterial metabolites characterized by their diazotetrahydro[b]benzofluorene and 2,6-dideoxyglycosidic residues. Owing to their high degrees of unsaturation, the lomaiviticins presented challenges to structure elucidation and were originally misassigned. In the originally purported structure, the bridging C-C bond is located at the ɑ-position of the C1 (C1′) cyclohexanone carbonyl. Accordingly, our lab developed a method to construct this bond through the bimolecular oxidative dimerization of complex enoxysilanes derived from monomeric diazofluorenes. In 2021, the structure revision of the lomaiviticins revealed that the dimeric bond now resides β to the cyclohexanone carbonyl. Due to the limited scope of methods for the β-functionalization of cyclic ketones and the now well-established stability of the diazofluorene under oxidative conditions, we devised a general oxidative dimerization approach for accessing the fully dimeric natural product(s).