Intramolecular Mannich and Michael Annulation Reactions of Lactam Derivatives Bearing Enals To Afford Bicyclic N-Heterocycles

Acid-catalyzed intramolecular vinylogous Mannich reactions and intramolecular Michael reactions affording pyrrolizinone-fused N-heterocycles from hydroxylactam derivatives bearing enals have been developed. Depending on the substituent on the hydroxylactam, the enal moiety acted either as a nucleophile (i.e., as an enol/enolate) or as an electrophile to react with the N-acyliminium ion or enamide generated from the hydroxylactam moiety, respectively. The reactions were demonstrated in the construction of fused N-heterocycles with 5- to 8-membered rings

Detection of enantiomers of chiral primary amines by 1H NMR analysis via enamine formation with an enantiopure γ-position aldol product of a β-keto ester

A 1H NMR analysis method that detects enantiomers of molecules bearing a primary amino group has been developed. The method uses a β-keto ester-derived probe that forms enamines with the amines and is able to discriminate enantiomers of functionalized amines and amines that have chiral centers at positions remote from the amine group

Varying the Directionality of Protein Catalysts for Aldol and Retro‐Aldol Reactions

Natural aldolase enzymes and created retro-aldolase protein catalysts often catalyze both aldol and retro-aldol reactions depending on the concentrations of the reactants and the products. Here, we report that the directionality of protein catalysts can be altered by replacing one amino acid. The protein catalyst derived from a scaffold of a previously reported retro-aldolase catalyst, catalyzed aldol reactions more efficiently than the previously reported retro-aldolase catalyst. The retro-aldolase catalyst efficiently catalyzed the retro-aldol reaction but was less efficient in catalyzing the aldol reaction. The results indicate that protein catalysts with varying levels of directionality in usually reversibly catalyzed aldol and retro-aldol reactions can be generated from the same protein scaffold