Effective irreversible alkylating reagents based on the structure of clavulones.
We describe the design and synthesis of alkylating reagents based on the structure of clavulones. They are composed of cross-conjugated dienone system and irreversibly reacted with two nucleophiles under mildly basic conditions via beta-elimination. Hydroxyl derivative 7b showed the highest reactivity toward thiols and showed the strongest cytotoxicity in Hela S3 cells among the three derivatives having a different protecting group at the tert-hydroxyl group.
Tanaka
Hiroshi
H
Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan.
Kitade
Makoto
M
Iwashima
Makoto
M
Iguchi
Kazuo
K
Takahashi
Takashi
T
D000478:Alkylation; D002455:Cell Division / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011454:Prostaglandins A / Q000138:chemical synthesis* / Q000494:pharmacology
D003432:Cross-Linking Reagents; D011454:Prostaglandins A; C046249:clavulones