- 作者: 忻凌偉,陳建維,張莉德
- 作者服務機構: Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei 10018, Taiwan, R.O.C.
- 中文摘要: Octahydro-1H-benzofuro[3,2-e]isoquinolines, which possess the ACNO partial structure of morphine, displayed potent oral analgesic and narcotic-antagonism activity. However, due to inefficiency in their synthesis the ACNO derivatives have not been developed for clinical use. Here, we report in detail the first asymmetric total synthesis of (-)-octahydro-1H-benzofuro[3,2-e]isoquinoline as exemplified by the preparation of (-)-1 and (-)-2. The key intermediate (+)-5-hydroxy-3,4,5,6,7,8-hexahydro-1H-isoquinoline-2-carboxylic acid ethyl ester ((+)-5) was prepared in 81% yield and with 100% ee by asymmetric reduction of 5-oxo-3,4,5,6,7,8-hexahydro-1H-isoquinoline-2-carboxylic acid ethyl ester (6) using RuCl[(R,R)-Tsdpen](p-cymene) as catalyst with a S/C of 200. The three chiral centers of ACNO skeleton were constructed via a reaction sequence of asymmetric transfer hydrogenation, Heck reaction, and catalytical hydrogenation, and all of these stereoselective reactions were metal-catalyzed (i.e. Ru, Pd, and Pt, respectively).
- 英文摘要: --
- 中文關鍵字: Asymmetric synthesis; Morphine; Partial structure; Heck reaction; Hydrogenation.
- 英文關鍵字: --