Stereoselective synthesis of pyroglutamate natural product analogs from α-Aminoacids and their anti-cancer evaluation

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

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1514-1530
Number of pages17
JournalAnti-Cancer Agents in Medicinal Chemistry
Volume13
Issue number10
DOIs
StatePublished - Dec 2013

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology
  • Cancer Research

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