Studies on Asymmetric Synthesis of Alkaloids from Poison-Dart Frogs

• Project/Area Number: 01571167
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: Tokyo College of Pharmacy
• Principal Investigator: KIBAYASHI Chihiro Tokyo College of Pharmacy, 薬学部, 教授 (80057330)
• Project Period (FY): 1989 – 1990
• Project Status: Completed (Fiscal Year 1990)
• Budget Amount: ¥2,100,000 (Direct Cost: ¥2,100,000); Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: Alkaloids from Poison-Dart Frogs / (-)-Indolizidine / (-)-Pumiliotoxin C / N-Acyl Nitroso Compound / Herero Diels Alder Reaction / Intramolecular Cyclization / Asymmetric Symthesis / プミリオトキシンC / デカヒドロキノリン / (-)-インドリチジンアルカロイド / アシルニトロソ化合物 / ヘテロディ-ルス-アルダ-反応 / 分子内環化付加反応 / オキサジノラクタム / 立体選択的側鎖導入

Research Abstract

More than 200 alkaloids have been isolated in minute quantity from the skin extracts of neotropical poison-dart frogs of the dendrobatid species The lack of availability of natural material and the fascinating biological activity of the compounds which have been studied, make these alkaloids ideal targets for total synthesis. In connection with studies aimed at total synthesis of optically active dendrobatid alkaloids, the author has chosen several (-)-indolizidines (in1989) and (-)-pumiliotoxin C (in1990) as target alkaloids. The synthetic plan is based on asymmetric intramolecular hetero Diels-Alder cycloaddition. Thus, the hydroxamic acid, prepared from (R)-citronellol, was subjected to hetero Diels-Alder reaction to afford the chiral oxazinolactam. Subsequent transformations including stereoselective introduction of the alkyl side chain to the resulting oxazinolactam led to the first chiral synthesis of (-)-indolizidines 205A, 207A, 209B, and 235B.
Otherwise, an alternative hetero Diels-Alder reaction of the hydroxamic acid, derived from L-glutamic acid in 8 steps, followed by several sequences including stereoselective introduction of alkyl side chain resulted in the stereoselective construction of the decahydroquinoline derivative. This product can be converted to objective pumiliotoxin C by one step involving deoxygenation.

Research Products

• [Publications] Yuji Shishido: "The Total Synthesis of (-)-Indolizidines 205A and 235B" J.Chem.Soc.,Chem.Commun.(1991)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yuji Shishido and Chihiro Kibayashi: "A Total Syntesis of (-)-Indolizidines 205A and 235B" J. Chem. Soc., Chem. Commun.(1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 樹林千尋,宍戸祐二: "Total Synthesis of(-)-Indolizidine 205A,207A,209B,235B via Intramolecular Hetero Diels-Alder Reaction with Acylnitroso Compounds" Tetrahedron Letters.