Study for Asymmetric Syntheses of Alkaloids with Nurotransmission Inhibitory Effects

1995 Fiscal Year Final Research Report Summary

• Project/Area Number: 06680559
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Bioorganic chemistry
• Research Institution: Osaka University
• Principal Investigator: IWATA Chuzo Osaka University, Pharmaceutical Sciences Professor, 薬学部, 教授 (60028842)
• Co-Investigator(Kenkyū-buntansha): MAEZAKI Naoyoshi Osaka University, Pharmaceutical Sciences Assistant Professor, 薬学部, 助手 (00229296) ; TANAKA Tatsuaki Osaka University, Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (40116059)
• Project Period (FY): 1994 – 1995
• Keywords: Pummerer-type reaction / vinylic sulfoxide / perhydrohistrionicotoxin / histrionicotoxin / asymmetric synthesis / neurotransmission inhibitor / intramolecular allylation

Research Abstract

Formal synthesis of perhydrohistrioniocotoxin 1, an alkaloid with the inhibitory effect against neurotransmission, was accomplished using an additive Pummerer reaction [1,2] and a carbonyl allylation reaction as crucial steps.
On treatment with allylmagnesium bromide, the vinylic sulfoxide 2 gave selectively the vinylic sulfide 3 (90% e.e.) by additive Pummerer reaction. The absolute configuration of the newly formed quaternary carbon was determined as S by converting it into (+) -malyngolide. Then, the vinylic sulfide 3 was converted into the aldehyde 4. Palladium-catalyzed intramolecular carbonyl aflylation of 4 proceeded diastereoselectively to afford 5 with the desired stereochemistry, thereby constructing the three contiguous asymmetric carbon centers simultaneously. Finally, the spiro compound 5 was converted into the known intermediate 6. Since 6 leads to (+) -1 in 6 steps by the method of Takahashi and coworkers [3], a formal synthesis of (+) -1 was accomplished. This synthetic route may be useful for the syntheses of histrionicotoxin and congeners and for the research on structure-activity relationship.
[1] C.Iwata et al., J.Chem.Soc., Chem.Commun., 1991,1408.
[2] C.Iwata et al., ibid., 1991,1049.
[3] K.Takahashi et al., Helv.Chim.Acta, 1982,65,252.

Research Products

• [Publications] N. Maezaki: "Two Types of Stereocontrol in the Formation of Spiro Skeletons via a Carbonyl Ene Reaction and a Palladium-catalyzed Carbonyl Allylation : a Formal Synthesis of (+) -Perhydrohistrionicotoxin" J. Chem. Soc.,Chem. Commun.1835-1836 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] N.Maezaki, H.Fukuyama, S.Yagi, T.Tanaka, and C.Iwata: "Two Types of Stereocontrol in the Formation of Spiro Skeletons via a Carbonyl Ene Reaction and a Palladium-catalyzed Carbonyl Allylation : a Formal Synthesis of (+) -Perhydrohistrionicotoxin" J.Chem.Soc., Chem.Commun.1835-1836 (1994)
  • Description: 「研究成果報告書概要(欧文)」より