Productive Syntheses of Privileged Scaffolds Inspired by the Recognition of a Diels-Alder Pattern Common to Three Classes of Natural Products.

Identification of a common Diels-Alder pattern in three classes of bioactive natural products led us to study the synthesis and cycloaddition of a new class of cyclic dienes readily available from β,γ-unsaturated lactams. A practical and readily scalable route to the parent p-methoxybenzyl-protected 6- and 7-membered β,γ-unsaturated lactams was developed. These were readily transformed into the corresponding O-silylated dienes, which were reacted with dimethyl and diethyl fumarate to yield stereoselectively highly functionalized bicyclic adducts.

Applications of NMR screening techniques to the pharmaceutical target Checkpoint kinase 1.

Ligand screening techniques based on NMR spectroscopy are not as sensitive as other commonly used methods like fluorescence, radiolabeling and surface plasmon resonance. However, using modern NMR instrumentation, they can achieve reliable screening under near physiological condition using as little as 4.6 nmol of receptor and 100 nmol of ligand.

Aryl-heteroaryl derivatives as novel wake-promoting agents.

In search of a next generation molecule to the novel wake-promoting agent modafinil, a series of aryl-heteroayl-derived wakefulness enhancing agents (in rats) was developed. From this work, compound 16 was separated into its enantiomers to profile them individually.