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

Author(s): Srinivas Tekkam , Mohammad A. Alam , Matthew J. Just , Steven M. Berry , Joseph L. Johnson , Subash C. Jonnalagadda , Venkatram R. Mereddy .

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 13 , Issue 10 , 2013

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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.

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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Article Details

VOLUME: 13
ISSUE: 10
Year: 2013
Page: [1514 - 1530]
Pages: 17
DOI: 10.2174/18715206113139990097
Price: $58

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