1989 Fiscal Year Final Research Report Summary

Synthetic Studies on the Antitumor Benzo[c]phenanthridine Alkaloids Directing toward Medicinals Development

Research Project

Project/Area Number	62870085
Research Category	Grant-in-Aid for Developmental Scientific Research
Allocation Type	Single-year Grants
Research Field	Chemical pharmacy
Research Institution	Chiba University
Principal Investigator	ISHII Hisashi Chiba Univ. Fac. of Pharm. Scien. Professor, 薬学部, 教授 (70009166)
Co-Investigator(Kenkyū-buntansha)	ISHIKAWA Tsutomu Res. Associate, 薬学部, 助手 (20114233) HARAYAMA Takashi Assoc. Professor, 薬学部, 助教授 (30025712)
Project Period (FY)	1987 – 1989
Keywords	Synthesis / Antitumor alkaloid / Chelerythrine / Propargyl ether / Claisen rearrangement / Furan ring formation / Furan ring cleavage
Research Abstract	1)Claisen Rearrangement of Aryl propargyl ether in the Presence of CsF. Claisen rearrangement of primary propargyl ether in the presence of CsF afforded exclusively the arylfuran derivated. The reaction condition was examined in detail using beta-naphtol derivatives (1) : (a)the best solvent is diethylaniline; (b)CsF is essential. A generality of the reaction was investigated using the compound(2-4). 2)Cleavage of Arylfuran Ring. Oxidative cleavage of furan ring using derivative (5)was investigated. Consequently, successive treatment of 5 with a stoichiometric amount of OsO_4,NaIO_4, and aq. NaHCO_3 solution provided the desired salicylaldehyde (6) in a good yield. 3)Synthetic Studies on Chelerythrine (8, R=Me, R'=H) and the related compounds. The compound (7) was prepared by two routes using Claisen rearrangement in the presence of CsF and then, oxidatively cleaved to salicylaldehyde derivatives, which was converted to chelerythrine (8, R=Me, R'=H). Synthesis of phenolic base (8, R=Me, R'=OH) was also examined from the viewpoint of antitumor activity and the key intermediate was prepared in a high yield. The biological assay of a various compounds including synthetic intermediates was under investigation.