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.
Anti-Cancer Agents in Medicinal Chemistry
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/18715206113139990097 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
ABC Transporter Inhibitors in Reversing Multidrug Resistance to Chemotherapy
Current Drug Targets The Role of Apoptosis in Tumor Progression and Metastasis
Current Molecular Medicine Negative Regulation of NEDD8 Conjugation Pathway by Novel Molecules and Agents for Anticancer Therapy
Current Pharmaceutical Design The Interaction of NK Cells and Dendritic Cells in the Tumor Environment: How to Enforce NK Cell & DC Action Under Immunosuppressive Conditions?
Current Medicinal Chemistry Cellular Senescence as a Target in Cancer Control
Current Cancer Therapy Reviews Molecular Targeted Approaches for Treatment of Pancreatic Cancer
Current Pharmaceutical Design The Control of Cell Cycle in Mouse Primordial Germ Cells: Old and New Players
Current Pharmaceutical Design Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View
Current HIV Research Proteomics on Fixed Tissue Specimens – A Review
Current Proteomics Advances in Immuno-PET for the Detection of Cancer and Assessment of Response to Therapy
Current Medicinal Chemistry Ginsenoside RB1 Reduces Neurologic Damage, is Anti-Apoptotic, and Down-Regulates p53 and BAX in Subarachnoid Hemorrhage
Current Neurovascular Research IL-15 and HIV Infection: Lessons for Immunotherapy and Vaccination
Current HIV Research Sleep and the Immune System
Current Immunology Reviews (Discontinued) NRF2-Dependent Glutamate-L-Cysteine Ligase Catalytic Subunit Expression Mediates Insulin Protection Against Hyperglycemia-Induced Brain Endothelial Cell Apoptosis
Current Neurovascular Research mTOR Inhibitors in Tuberous Sclerosis Complex
Current Neuropharmacology The Link Between Conventional and Novel Anti-Cancer Therapeutics with Thrombotic Microangiopathy
Drug Metabolism Letters Neuropsychiatric Systemic Lupus Erythematosus
Current Neuropharmacology Individualized Treatment Planning in Oncology: Role of PET and Radiolabelled Anticancer Drugs in Predicting Tumour Resistance
Current Pharmaceutical Design The Offer of Chemistry to Targeted Therapy in Cancer
Recent Patents on Biotechnology Diagnostic and Therapeutic Applications of Radiolabeled Somatostatin Analogs: Current Status in an Oncology Center
Current Pharmaceutical Design