Synthesis of Poison-Frog Alkaloids and Their Pharmacological Effects at Neuronal Nicotinic Acetylcholine Receptors
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Naoki Toyooka*,1, Hiroshi Tsuneki1, Soushi Kobayashi1, Zhou Dejun1, Masashi Kawasaki2, Ikuko Kimura1, Toshiyasu Sasaoka1 and Hideo Nemoto
- چاپ و سال / کشور: 2007
Description
The flexible and efficient enantioselective synthesis of poison-frog alkaloids has been described using the highly stereoselective conjugate addition reactions as the key step. Several 5,8-disubstituted indolizidines and 1,4-disubstituted quinolizidines have been synthesized according to this strategy. Furthermore, 5,6,8-trisubstituted indolizidne type of poison-frog alkaloid 223A and unique tricyclic poison-frog alkaloid 205B have also been synthesized by sequential use of the above key conjugate addition reaction. Investigations of inhibitory effects of synthetic poison-frog alkaloids on neuronal nicotinic acetylcholine receptors have been conducted, and we found that most of the synthetic compounds showed inhibitory effects on the neuronal nicotinic acetylcholine receptors. Especially, the 5,8-disubstituted indolizidine 235B' inhibited the ..4..2-neuronal nicotinic acetylcholine receptors in highly subtype-selective manner. These results suggested that the synthetic alkaloid 235B' is a promising lead compound for the drugs designed to treat cholinergic disorders such as autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
Current Chemcial Biology, 2007, 1, 97-114
