Title:Stereoselective Synthesis of Pyroglutamate Natural Product Analogs from α- Aminoacids and their Anti-Cancer Evaluation
Volume: 13
Issue: 10
Author(s): Srinivas Tekkam, Mohammad A. Alam, Matthew J. Just, Steven M. Berry, Joseph L. Johnson, Subash C. Jonnalagadda and Venkatram R. Mereddy
Affiliation:
Keywords:
Pyroglutamates (γ-carboxy-γ-lactams), heterobicyclic compounds, diastereoselective dihydroxylation, regioselective regioselective
deoxygenation, lactonization, threonine derived oxazole, substrate controlled alkylation, Baylis-Hillman reaction, boronic acids.
Abstract: Alkylation of α-amino acid derived iminoesters with Baylis-Hillman (BH) reaction template based allyl bromides/allyl acetates
followed by acidic hydrolysis furnished α-methylene-β-substituted-pyroglutamates and α-alkylidene pyroglutamates respectively.
Application of these methodologies has been demonstrated in the synthesis of fused [3.2.0]-γ-lactam-β-lactones. Further, substrate
controlled stereoselective alkylation of L-threonine derived oxazoles with BH reaction based allyl bromides and acetates yielded optically
pure α-methylene-β-substituted pyroglutamates, and α-alkylidene pyroglutamates. These methodologies have been applied in the
preparation of chiral [3.2.0] heterobicyclic pyroglutamates containing hydroxyethyl side chain. All the synthesized pyroglutamates have
been evaluated for their anti-cancer and enzyme proteasome inhibition activity.
