石杉碱甲的合成研究进展
收稿日期: 2013-06-05
修回日期: 2013-07-18
网络出版日期: 2013-07-26
Progresses in the Total Synthesis of Huperzine A
Received date: 2013-06-05
Revised date: 2013-07-18
Online published: 2013-07-26
石杉碱甲是中国独创的治疗老年痴呆症的药物。由于其显著的疗效，长期以来，一直受到人们的关注和研究. 目前石杉碱甲在美国已经进入三期临床研究，而在中国也已获批上市并进入四期临床. 由于石杉碱甲在千层塔中的含量仅为万分之一左右，且千层塔的生长周期较长，所以石杉碱甲的化学合成将成为获得该药物的一种有效途径. 二十多年来，化学合成石杉碱甲从消旋化合成到手性合成，从毫克级放大到几百克级合成都体现了这一领域的长足发展. 其合成工艺和路线也在安全性、实用性方面大为改善. 系统综述了1989年到2013年间石杉碱甲化学合成的进展，以期为进一步完善石杉碱甲化学合成提供参考.
郑书岩 , 郁春辉 , 沈征武 . 石杉碱甲的合成研究进展[J]. 有机化学, 2013 , 33(11) : 2261 -2270 . DOI: 10.6023/cjoc201306006
Huperzine A has been widely used for the treatment of alzheimer in China, and has attracted widespread attention. It has been entered into phase 3 investigation in US and phase 4 investigation in China for the treatment of alzheimer and related disease. Due to the trace content in the herb Huperzia serrata, the chemical synthesis of huperzine A becomes the attractive option for drug supply. During the past two decades, significant progresses have been achieved for the stereoselective synthesis of (－)-huperzine A. The total synthesis of hundreds of grams of (－)-huperzine A has been achieved recently. In addition to the efficiency of the synthesis, the safety of the process was also significantly improved. The progresses of the total synthesis of huperzine A made from 1989 to 2013 are comprehensively reviewed in this paper.
Key words： huperzine A; chemical synthesis; review
[1] Tang,X.-X.; Han,Y.-F.; Chen,X.-P.; Zhu,X.-D.Acta Pharmacol.Sinica 1986,7,507 (in Chinese).(唐希灿,韩怡凡,陈小萍,朱晓东,中国药理学报,1986,7,507).
[2] (a) Bai,D.-L.; Tang,X.-C.; He,X.-C.Curr.Med.Chem.2000,7,355.
(b) Ma,X.; Tan,C.; Zhu,D.; Gang,D.-R.J.Ethnopharmacol.2006,104,54.
[3] (a) Zeng,F.-X.; Jiang,H.-L.; Yang,Y.-S.; Chen,K.-X.; Ji,R.-Y.Prog.Chem.2000,12,63 (in Chinese).(曾繁星,蒋华良,杨玉社,陈凯先,稽汝运,化学进展,2000,12,63.
(b) Wang,H.-X.; Wang,J.Chin.Wild Plant Res.2001,20,4 (in Chinese).(王洪新,王键,中国野生植物资源,2001,20,4.)
[4] Ha,G.-T.; Wong,R.-K.; Zhang,Y.Chem.Biodiversity 2011,8,1189.
[5] Qian,L.-G.; Ji,R.-Y.Tetrahedron Lett.1989,30,2089.
[6] (a) Xia,Y.; Kozikowski,A.P.J.Am.Chem.Soc.1989,111,4116.(b) Kozikowski,A.P.,Xia,Y.; Reddy,E.R.; Tuckmantel,W.; Hanin,I.; Tang,X.-C.J.Org.Chem.1991,56,4636.
[7] Yamada,F.; Kozikowski,A.P.; Reddy,E.R.; Pang,Y.P.; Miller,J.H.; Mckinney,M.J.Am.Chem.Soc.1991,113,4695.
[8] Chen,W.-P.; Yang,F.-Q.Chin.J.Med.Chem.1995,15,10 (in Chinese).(陈卫平,杨福秋,中国药物化学杂志,1995,15,10.)
[9] (a) Kaneko,S.; Yoshino,T.; Katoh,T.; Terashima,S.Heterocycles 1997,46,27.
(b) Kaneko,S.; Yoshino,T.; Katoh,T.; Terashima,S.Tetrahe-dron 1998,54,5471.
[10] Pan,Q.-B.; Ma,D.-W.Chin.J.Chem.2003,21,793.
[11] Ding,X.-H.; Li,X.; Liu,D.; Cui,W.-C.; Ju,X.; Wang,S.-Z.; Yao,Z.-J.Tetrahedron 2012,68,6240.
[12] (a) Kozikowski,A.P.; Campiani,G.; Aagaard,P.; Mckinney,M.J.Chem.Soc.,Chem.Commun.1993,10,860.
(b) Campiano,G.; Sun,L.Q.; Kozikowski,A.P.J.Org.Chem.1993,58,7660.
[13] (a) Huang,Y.; Lu,X.Tetrahedron Lett.1988,29,5663.
(b) Gravel,D.; Bennit,S.,Kumanovic,S.; Sivaramakrishnan,H.Tetrahedron Lett.1992,33,1403.
[14] Kaneko,S.; Yoshino,T.; Katoh,T.; Terashima,S.Tetrahedron: Asymmetry 1997,8,829.
[15] He,X.-C.; Wang,B.; Bai,D.-L.Tetrahedron Lett.1998,39,411.
[16] He,X.-C.; Wang,B.; Yu,G.-L.; Bai,D.-L.Tetrahedron: Asymmetry 2001,12,3213.
[17] (a) Hanudrechy,A.; Chassaing,C.; Riche,C.; Langlois,Y.Tetrahedron 2000,56,3181.
(b) Chassaing,C.; Hanudrechy,A.; Langlois,Y.Tetrahedron Lett.1999,40,8805.
[18] Tudhope,S.R.; Bellamy,J.A.; Ball,A.; Rajasekar,D.; Aza-di-Ardakani,M.Org.Process Res.Dev.2012,16 (4),635.
[19] (a) Foricher,Y.; Mann,J.Tetrahedron Lett.2000,41,2007.
(b) Kelly,S.A.; Foricher,Y.; Mann,J.; Bentley,J.M.Org.Biomol.Chem.2003,1,2865.
(c) Lucey,C.; Kelly,S.A.; Mann,J.Org.Biomol.Chem.2007,5,301.
[20] Ding,R.; Sun,B.-F.; Lin,G.-Q.Org.Lett.2012,14(17),4446.
[21] Caprio,V.; Mann,J.J.Chem.Soc.,Perkin Trans.1 1998,3151.
[22] Tuckmantel,W.; Kozikowski,A.P.US 6271379,2001 [Chem.Abstr.2001,135,153000].
[23] Moe Tun,M.K.; Wüstmann,D.J.; Herzon,S.B.Chem.Sci.2011,2,2251.
[24] (a) Moe,T.-M.K.; Herzon,S.B.J.Org.Chem.2012,77(20),9422.
(b) Lee,H.W.; Ji,S.K.; Lee,I.-Y.C.; Lee,J.H.J.Org.Chem.1996,61,2542
[25] Lee,Y.-C.; Jung,M.-H.; Lee,H.-W.; Yang,J.-Y.Tetrahedron Lett.2002,43,2407.
[26] (a) Snider,B.B.; Mohan,R.; Kates,S.A.J.Org.Chem.1985,50,3659.
(b) Snider,B.B.; Cole,B.M.J.Org.Chem.1995,60,5376.
[27] Ward,J.; Caprio,V.Tetrahedron Lett.2006,47,553.
[28] (a) Wark,J.; Johnson,A.B.; Clark,G.R.,Caprio,V.Synthesis 2009,3411.
(b) Ward,J.; Caprio,V.Heterocycles 2009,79,791.
[29] Koshiba,T.; Yokoshima,S.; Fukuyama,T.Org.Lett.2009,11(22),5354.
[30] White,J.D.; Li,Y.; Kim,J.; Terinek,M.Org.Lett.2013,15(4),882.
[31] Xu,H.M.S.Thesis,Northwestern University,Xi'an,2007 (in Chinese).(许慧,硕士论文,西北大学,西安,2007.)
/
| 〈 |
|
〉 |
