Synthetic method and biological activities of cis-fused alpha-methylene gamma-lactones.
A reliable method was developed for the synthesis of cis-fused alpha-methylene gamma-lactones via alpha-methyl gamma-lactones. Bromination of alpha-methyl gamma-lactones with LDA/CBr(4) or TMSOTf/PTAB and successive dehydrobromination with DBU or TBAF of the resulting alpha-bromo-alpha-methyl gamma-lactones gave the desired alpha-methylene gamma-lactones in high yield. This method was successfully applied to the synthesis of biologically active compounds. alpha-Methylene gamma-lactone derivatives 1c, 2c, 4c, and 17 showed cell growth inhibitory activity to P388 lymphocytic leukemia. They also showed significant activities to crop diseases. Thus, alpha-methylene gamma-lactone 1c showed preventive activity in controlling scab of apple caused by Venturia inaequalis. alpha-Methylene gamma-lactones 2c, 4c, 17, and 18 also showed significant preventive activities in controlling damping off of cucumber caused by Pythium aphanidermatum.
Higuchi
Yohsuke
Y
Graduate School of Science and Technology, and Department of Chemistry and Chemical Engineering, Faculty of Engineering, Niigata University, 2-8050 Ikarashi, Niigata 950-2181, Japan.
Shimoma
Fumito
F
Ando
Masayoshi
M
D000818:Animals; D000935:Antifungal Agents / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D001965:Bromides / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D018553:Cucumis sativus; D004354:Drug Screening Assays, Antitumor; D007783:Lactones / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D007941:Leukemia P388; D051379:Mice; D015394:Molecular Structure; D012275:Oryza; D010935:Plant Diseases; D011775:Pythium / Q000187:drug effects; D012232:Rhizoctonia / Q000187:drug effects; D013237:Stereoisomerism; D014908:Triticum
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D001965:Bromides; D007783:Lactones; C416683:methylene-lactone