Total Synthesis and Antidepressant Activities of Laetispicine and Its Derivatives 英文参考文献.docVIP

Molecules 2012, 17, 1425-1436; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Total Synthesis and Antidepressant Activities of Laetispicine and Its Derivatives Shuyi Yao 1, Hui Xie 2, Li Zhang 1, Tao Meng 1, Yongliang Zhang 1, Xin Wang 1, Lin Chen 1, Shengli Pan 2 and Jingkang Shen 1,* 1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China 2 School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China * Author to whom correspondence should be addressed; E-Mail: jkshen@; Tel.: +86-21-5080-6600 ext. 5407; Fax: +86-21-5080-7088. Received: 4 January 2012; in revised form: 16 January 2012 / Accepted: 30 January 2012 / Published: 3 February 2012 Abstract: The first total synthesis of laetispicine (1a), an amide alkaloid isolated from the stems of Piper laetispicum C.DC (Piperaceae), and the synthesis of some of its derivatives were described. Based on the evaluation of antidepressant activities in the forced swimming test, compounds 1h and 1i were identified as potent and safe antidepressant lead compounds. Keywords: laetispicine derivatives; antidepressant; total synthesis; forced swimming test 1. Introduction Natural products have traditionally played an important role in drug discovery and are the basis of many important therapeutics that have found broad use in the clinic [1]. Extensive studies to search among natural products for new antidepressants that possess both high efficacy and safety have been carried out [2,3]. Laetispicine (Figure 1) was first isolated in 2002 by Pan and co-workers from Piper laetispicum C.DC., a herb growing in China and parts of southeast Asia [4,5]. Piper laetispicum C.DC. is one of the species in pepper family and had been used for invigorating circulation and reducing stasis, detumescence and as an analgesi