Stereoselective Synthesis of Pyroglutamate Natural Product Analogs from α- Aminoacids and their Anti-Cancer Evaluation

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.

Cite this article as:

Tekkam Srinivas, Alam A. Mohammad, Just J. Matthew, Berry M. Steven, Johnson L. Joseph, Jonnalagadda C. Subash and Mereddy R. Venkatram, Stereoselective Synthesis of Pyroglutamate Natural Product Analogs from α- Aminoacids and their Anti-Cancer Evaluation, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (10) . https://dx.doi.org/10.2174/18715206113139990097