Directing Aβ42 to adopt a conformation that is free from aggregation and cell toxicity is an attractive and viable strategy to design therapeutics for Alzheimer’s disease. Over the years, extensive...

Here, we are reporting the spontaneous transformation of active esters of N-Boc protected E-α,β-unsaturated γ-amino acids into corresponding Z-α,β-unsaturated γ-lactams with concomitant E→Z isomerization in the presence of weak base....

Here, we are reporting a single-step transformation of N-protected α,β-unsaturated γ-amino amides into 5,5-disubstituted γ-lactams through a base-mediated new molecular rearrangement. In contrast to the known N- to C­(O) cyclization of saturated γ-amino acids into corresponding γ-lactams, the new rearrangement involves the cyclization between N-terminal Cγ- to C-terminal amide N. The cyclization process was initiated by the migration of double bond from α,β → β,γ position. The enamine–imine tautomerization of the new β,γ-double bond and subsequent 5-exo-trig cyclization of terminal amide leads to the formation of N-protected 5,5-disubstituted γ-lactam. The structures of various γ-lactams obtained from the rearrangement were studied in single crystals. Overall, the results reported here demonstrate the facile and single-step transformation of N-protected α,β-unsaturated γ-amino amides into γ-lactams and provided an excellent opportunity to construct small-molecule peptidomimetics.

Utilization of the Wittig reaction to synthesize conjugative multiple double bonds is rare. We examined the utility of the Wittig reaction to construct conjugative two and three carbon-carbon double bonds...