Abstract
The flexible and efficient enantioselective synthesis of poison-frog alkaloids has been described using the highly stereoselective conjugate addition reactions as the key step. Several 5,8-disubstituted indolizidines and 1,4-disubstituted quinolizidines have been synthesized according to this strategy. Furthermore, 5,6,8-trisubstituted indolizidne type of poison-frog alkaloid 223A and unique tricyclic poison-frog alkaloid 205B have also been synthesized by sequential use of the above key conjugate addition reaction. Investigations of inhibitory effects of synthetic poison-frog alkaloids on neuronal nicotinic acetylcholine receptors have been conducted, and we found that most of the synthetic compounds showed inhibitory effects on the neuronal nicotinic acetylcholine receptors. Especially, the 5,8-disubstituted indolizidine 235B inhibited the α4 β2-neuronal nicotinic acetylcholine receptors in highly subtype-selective manner. These results suggested that the synthetic alkaloid 235B is a promising lead compound for the drugs designed to treat cholinergic disorders such as autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
Keywords: Michael-type conjugate addition, indolizidine, quinolizidine, piperidone synthesis, nicotinic acetylcholine receptors (nAChRs)
Current Chemical Biology
Title: Synthesis of Poison-Frog Alkaloids and Their Pharmacological Effects at Neuronal Nicotinic Acetylcholine Receptors
Volume: 1 Issue: 1
Author(s): Naoki Toyooka, Hiroshi Tsuneki, Soushi Kobayashi, Zhou Dejun, Masashi Kawasaki, Ikuko Kimura, Toshiyasu Sasaoka and Hideo Nemoto
Affiliation:
Keywords: Michael-type conjugate addition, indolizidine, quinolizidine, piperidone synthesis, nicotinic acetylcholine receptors (nAChRs)
Abstract: The flexible and efficient enantioselective synthesis of poison-frog alkaloids has been described using the highly stereoselective conjugate addition reactions as the key step. Several 5,8-disubstituted indolizidines and 1,4-disubstituted quinolizidines have been synthesized according to this strategy. Furthermore, 5,6,8-trisubstituted indolizidne type of poison-frog alkaloid 223A and unique tricyclic poison-frog alkaloid 205B have also been synthesized by sequential use of the above key conjugate addition reaction. Investigations of inhibitory effects of synthetic poison-frog alkaloids on neuronal nicotinic acetylcholine receptors have been conducted, and we found that most of the synthetic compounds showed inhibitory effects on the neuronal nicotinic acetylcholine receptors. Especially, the 5,8-disubstituted indolizidine 235B inhibited the α4 β2-neuronal nicotinic acetylcholine receptors in highly subtype-selective manner. These results suggested that the synthetic alkaloid 235B is a promising lead compound for the drugs designed to treat cholinergic disorders such as autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
Export Options
About this article
Cite this article as:
Toyooka Naoki, Tsuneki Hiroshi, Kobayashi Soushi, Dejun Zhou, Kawasaki Masashi, Kimura Ikuko, Sasaoka Toshiyasu and Nemoto Hideo, Synthesis of Poison-Frog Alkaloids and Their Pharmacological Effects at Neuronal Nicotinic Acetylcholine Receptors, Current Chemical Biology 2007; 1 (1) . https://dx.doi.org/10.2174/2212796810701010097
DOI https://dx.doi.org/10.2174/2212796810701010097 |
Print ISSN 2212-7968 |
Publisher Name Bentham Science Publisher |
Online ISSN 1872-3136 |
- 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
- Announcements
Related Articles
-
Progress and Outlooks in a Genetic Absence Epilepsy Model (WAG/Rij)
Current Medicinal Chemistry Interleukin-1β Increases Release of Endothelin-1 and Tumor Necrosis Factor as Well as Reactive Oxygen Species by Peripheral Leukocytes During Experimental Subarachnoid Hemorrhage
Current Neurovascular Research Recent Advances and Patents on Nanoscale Systems and Triggerable Drug Delivery in Medical Devices
Recent Patents on Biomedical Engineering (Discontinued) Nanoparticulate Drug Delivery in Pregnancy: Placental Passage and Fetal Exposure
Current Pharmaceutical Biotechnology Editorial (Thematic Issue: The Activity of Products From Cnidaria: A Therapeutic Tool in Neurological Diseases? Part II)
Central Nervous System Agents in Medicinal Chemistry Investigating Serotonergic Function Using Positron Emission Tomography: Overview and Recent Findings
Current Pharmaceutical Design Insights into Anti-Trypanosomal Agents Based on Synthetic Glycoconjugates
Current Topics in Medicinal Chemistry Complexities of Glucuronidation Affecting In Vitro-In Vivo Extrapolation
Current Drug Metabolism Psychiatric Disorders Associated with FXTAS
Current Psychiatry Reviews Cardioembolic Stroke: Clinical Features, Specific Cardiac Disorders and Prognosis
Current Cardiology Reviews Concerns with AED Conversion: Comparison of Patient and Physician Perspectives
Current Neuropharmacology MicroRNAs Involved in Oxidative Stress Processes Regulating Physiological and Pathological Responses
MicroRNA Pharmacological Approaches for Treatment-resistant Bipolar Disorder
Current Neuropharmacology Gap Junctions as Therapeutic Targets in Brain Injury Following Hypoxia- Ischemia
Recent Patents on CNS Drug Discovery (Discontinued) Is There Any Scientific Basis of Hawan to be Used in the Alzheimer’s Disease Prevention/Cure?
Current Traditional Medicine Inhibition of Monoamine Neurotransmitter Transporters and Central Nervous System Stimulation Induced by Synthetic Local Anesthetics and Cocaine: A Comparative Review-Update
Current Medicinal Chemistry - Central Nervous System Agents Extracellular Vesicles in Glioblastoma: Role in Biological Processes and in Therapeutic Applications
Current Cancer Drug Targets Current Status of Magnetite-Based Core@Shell Structures for Diagnosis and Therapy in Oncology Short running title: Biomedical Applications of Magnetite@Shell Structures
Current Pharmaceutical Design A Systematic Approach to Hypertensive Urgencies and Emergencies
Current Hypertension Reviews Dietary and Plant Polyphenols Exert Neuroprotective Effects and Improve Cognitive Function in Cerebral Ischemia
Recent Patents on Food, Nutrition & Agriculture