A novel, isoform-selective inhibitor of histone deacetylase 8 (HDAC8) has been discovered by the repurposing of a diverse compound collection. Medicinal chemistry optimization led to the identification of a highly potent (0.8 nM) and selective inhibitor of HDAC8.

We have developed an automated photochemical microfluidics platform that integrates a 1 kW high-pressure Hg vapor lamp and allows for analytical pulse flow or preparative continuous flow reactions. Herein, we will discuss the use of this platform toward the discovery of new chemotypes through multidimensional reaction screening. We will highlight the ability to discretely control wavelengths with optical filters, allowing for control of reaction outcomes.

Reaction screening of nucleophilic reaction partners for addition to N-diphenylphosphinylimines employing lanthanum (III) triflate as catalyst and trifluoroacetic anhydride (TFAA) as activator is reported. A number of tandem processes leading to novel chemotypes including aza-Prins/intramolecular Friedel-Crafts annulations have been identified and both reaction scope and mechanism further investigated.

. -N-Phosphinylimines such as (I) undergo nucleophilic additions such as aza-Friedel-Crafts reactions, aza-ene reactions, tandem aza-Prins/Friedel-Crafts reactions and tandem reactions with 1,3-dienes to give a series of non-cyclized and cyclized products or the bis-indan (XIX). The protected amino group of (VII) can be incorporated into the alkaloid framework (VIII). -(KINOSHITA, H.; INGHAM, O.