Recent advances in the study of(-)clausenamide:chemistry,biological activities and mechanism of action  

作　　者：Shi-feng Chu Jun-tian Zhang 

机构地区：[1]Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

出　　处：《Acta Pharmaceutica Sinica B》2014年第6期417-423,共7页药学学报（英文版）

摘　　要：Clausenamide(clau)is one of seven novel compounds isolated from Clausena lansium(Lour)skeels.Clau is unusual in that it contains 4 chiral centers yielding 8 pairs of enantiomers.After identification of the configuration of these enantiomers,the synthesis of 16 enantiomers,including optically active clau and(+)and(-)clau was carried out.During this study,many stereochemical and synthetic difficulties were solved and the Baldwin principle was updated.Production scale is now sufficient to meet the needs of clinical practice.In a pharmacological study numerous models and indicators showed that(-)clau is the active enantiomer,while(+)clau is inactive and elicits greater toxicity than(-)clau.The principal pharmacological effects of(-)clau are to increase cognition,demonstrated in ten models of memory impairment,as well as to inhibitβ-amyloid(Aβ)toxicity,blocking neurofibrillary tangle formation by inhibiting the phosphorylation of tau protein.This anti-dementia effect is characterized by increased synaptic plasticity both in efficacy and in structure and provides new support for the theory that synaptic loss is the main cause of dementia.(-)Clau is considered to be a promising drug candidate for treatment of Alzheimer's disease and other neurodegenerative disorders.

关 键 词：(-)Clausenamide ENANTIOMERS COGNITION Alzheimer's disease pathology Tau High phosphorylation Synaptic plasticity 

分 类 号：O62[理学—有机化学]