Comparing the anion binding of 4-amido- with 4-amino-1,8-naphthalimides.

The synthesis and evaluation of a new anion receptor based on the 4-amido-1,8-naphthalimide scaffold is described. The findings indicate that the amide N-H is an enhanced H-bond donor but is otherwise restricted in its ability to participate in the binding of simple anions.

Direct Amidation to Access 3-Amido-1,8-Naphthalimides Including Fluorescent Scriptaid Analogues as HDAC Inhibitors.

Methodology to access fluorescent 3-amido-1,8-naphthalimides using direct Buchwald-Hartwig amidation is described. The protocol was successfully used to couple a number of substrates (including an alkylamide, an arylamide, a lactam and a carbamate) to 3-bromo-1,8-naphthalimide in good yield. To further exemplify the approach, a set of scriptaid analogues with amide substituents at the 3-position were prepared. The new compounds were more potent than scriptaid at a number of histone deacetylase (HDAC) isoforms including HDAC6. Activity was further confirmed in a whole cell tubulin deacetylation assay where the inhibitors were more active than the established HDAC6 selective inhibitor Tubastatin. The optical properties of these new, highly active, compounds make them amenable to cellular imaging studies and theranostic applications.

Fluorinated Ketones as Trapping Reagents for Visible-Light-Induced Singlet Nucleophilic Carbenes.

Singlet nucleophilic carbenes (SNCs) containing only one heteroatom donor remain underutilized in chemical synthesis. We recently discovered that visible-light-induced SNC intermediates can be trapped by fluorinated ketones via 1,2-carbonyl addition to afford benzoin-type products. This discovery represents a rare example of nucleophilic carbenes reacting with ketones and delivers an efficient, user-friendly, and scalable process for accessing fluorinated tertiary alcohol derivatives driven only by light circumventing the use of exogenous catalysts or additives.