The potent anti-inflammatory agent, BIRT-377, contains an α-quaternary center in a hydantoin ring. Due to requirements for clinical testing on enantiopure compounds, the need for enantioselective routes to chiral compounds, such as BIRT-377, are highly sought. Enantioselective syntheses of compounds containing α-quaternary amine moieties are difficult because steric hinderance precludes the use of many standard synthetic procedures. Enzymatic desymmetrization of α,α-disubstituted malonic esters, followed by Curtius rearrangement, has been shown to provide access to α-quaternary amino acid derivatives, often with high enantiopurity. Thus, using this methodology a stereodivergent synthesis of BIRT-377 was accomplished, affording both enantiomers in high optical purity.

Acetylenic sulfones have been employed in sequential conjugate addition and cyclization reactions in our group to synthesize various nitrogen-containing heterocycles. We attempted to extend this methodology to the synthesis of the alkaloid gephyrotoxin; however, we were unable to obtain a β-amino ester compound required for a key conjugate addition step.