1990 Fiscal Year Final Research Report Summary

Molecular Design of Novel Type of Anticancer Alkylating Agents. Synthesis of Oligonucleotides Bearing Two Intercalator Groups.

Research Project

Project/Area Number	01571161
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Chemical pharmacy
Research Institution	KITASATO UNIVERSITY
Principal Investigator	ZEN SHONOSUKE KITASATO UNIV., Pharmaceutical Sci., Professor, 薬学部, 教授 (80050342)
Co-Investigator(Kenkyū-buntansha)	HIROTANI SEIKO KITASATO UNIV., Pharmaceutical Sci., Assistant, 薬学部, 助手 (20050594) HIROOKA MOTOKO KITASATO UNIV., Pharmaceutical Sci., Assistant, 薬学部, 助手 (20050578) HARADA KAZUHO KITASATO UNIV., Pharmaceutical Sci., Assistant, 薬学部, 助手 (00189698) KAJI EISUKE KITASATO UNIV., Pharmaceutical Sci., Lecturer, 薬学部, 講師 (60050598)
Project Period (FY)	1989 – 1990
Keywords	Bisintercalator / Oligonucleotide / Pyridocarbazole / Ring transformation
Research Abstract	With the aim of developing a novel type of anticancer alkylating agents, e.g. oligonucleotides bearing two intercalator groups (1), Synthetic routes of ellipticine (2), 9-hydroxyellipticine (3), and 11-fluoromethyl-9-hyaroxy-5-methy1-6H-pyrido[4,3-b]carbazole (4) was investigated in the following manners. 1) Ellipticine (2) was synthesized starting from 3-ethyl-4-methylpyridine. 9-Hydroxyellipticine (3) was also attempted to synthesize in a similar manner, however, there are several steps to compete the total synthesis of 3. 2) In the case of total synthesis of 4, the key compound, pyrido[4,3-b]-carbazole dervative (6), was obtained in six steps starting from 5- methoxyindole. 3) Another approach to synthesize 4 employing the ring transformation of isoxazoline N-oxide to 3H--indole was investigated. In the course of this project, we found several new ring transformations of isoxazoline Nーoxide. 4) The sugar moiety (5) was prepared and the synthesis of oligoncleotides by the condensation of these intercalators with 5 will be investigated.