Stereoselective Synthesis of Pyroglutamate Natural Product Analogs from α- Aminoacids and their Anti-Cancer Evaluation
Mohammad A. Alam,
Matthew J. Just,
Steven M. Berry,
Joseph L. Johnson,
Subash C. Jonnalagadda,
Venkatram R. Mereddy.
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.
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.
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