title: Stereoselective synthesis of pyroglutamate natural product analogs from α- aminoacids and their anti-cancer evaluation.
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.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Tekkam
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Alam
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Just
authors.forename: Steven M
authors.initials: SM
authors.lastname: Berry
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Subash C
authors.initials: SC
authors.lastname: Jonnalagadda
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN 55812, USA. vmereddy@d.umn.edu.
authors.forename: Venkatram R
authors.initials: VR
authors.lastname: Mereddy
mesh_terms: D000085:Acetates / Q000737:chemistry; D000478:Alkylation; D000498:Allyl Compounds / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D006868:Hydrolysis; D007783:Lactones / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000085:Acetates; D000498:Allyl Compounds; D000596:Amino Acids; D001688:Biological Products; D007783:Lactones; D010080:Oxazoles; C498551:allyl acetate; D046988:Proteasome Endopeptidase Complex; C050431:allyl bromide; D011761:Pyrrolidonecarboxylic Acid