HO HH OH R H CH2o H2NOC CONH2 Me Me Me H2NOC Me H H2NOC Me Me Me CONH Me NH Me HO H H H H CH,OH 维生素B2
5. K. C. Nicolaou s.L. Schreiber >K. C Nicolaou, et al. The art and science of total synthesis at the dawn of twenty-first century, angew. Chem. Int. Ed Engl.,2002,39,44 >S. L. Schreiber, et al. Target-oriented and diversity oriented organic synthesis in drug discovery, Science, 2000, 287.1964 高立体选择性( High Stereoselectivity) 原子经济性反应( Atom Economical reaction) 绿色化学( Green Chemistry)
5. K. C. Nicolaou & S. L. Schreiber ➢ K. C. Nicolaou, et al. The art and science of total synthesis at the dawn of twenty-first century, Angew. Chem. Int. Ed. Engl., 2002, 39, 44 ➢ S. L. Schreiber, et al. Target-oriented and diversityoriented organic synthesis in drug discovery, Science, 2000, 287,1 964 高立体选择性（High Stereoselectivity) 原子经济性反应（Atom Economical Reaction) 绿色化学 （Green Chemistry)
有机合成化学的发展趋势 1.新试剂、新反应、新方法的发现永无止境 Epibatidine的研究 ED50: 0.005 mg/kg s.c. 1.5 mg/kg i.p. isolated from skins of the Ki:(+)0.045nM (-)0.058nM, Daly, John w.etaL. L. Am. chem. Soc (1992),114(9),3475-8 Epibatidine First total synthesis of (+)and (-)-EP First patent: Corey. E.J. et aL. USA. Daly, John w. et al J. Org. Chem.(1993). Us845042(1993) 58(21),5600-2 General Introduction of epibatidine
二、有机合成化学的发展趋势 1. 新试剂、新反应、新方法的发现永无止境 H N N Cl Epibatidine isolated from skins of the Ecuadoran poison frog Epipedobates tricolor Daly, John W. etal. J. Am. Chem. Soc. (1992), 114(9), 3475-8 ED50: 0.005 mg/kg s.c. 1.5 mg/kg i.p. Daly, John W. et al. Ki: (+) 0.045nM; (-) 0.058 nM, in mice, hot plate test nAChR Corey, E. J. et al. USA. J. Org. Chem. (1993), 58(21), 5600-2. First patent: US 845042(1993) First total synthesis of (+)and (-)-EP General Introduction of Epibatidine • Epibatidine 的研究
R R R R BOc H SO,Tol SO,Tol NR R R Y(OTO3
N R" R' + NR R" R" R NBoc SO2Tol H NBoc SO2Tol + N R" R' + NR R" R" R N R" R' + N R" Y(OTf)3 R
Y(OTD3-catalyzed novel Mannich reaction of N-alkoxy carbonylpyrroles, formaldehyde and primary amine hydrochlorides N-R Y(OTD3(10%mmole) +R'CHO+R".HCI R CHNHR N C X Zhuan, J C. Dong, T M. Cheng,R. T Li, Tetrahedron Letters,2001,43(3),461-463
Y(OTf)3 -catalyzed novel Mannich reaction of N-alkoxycarbonylpyrroles, formaldehyde and primary amine hydrochlorides C. X. Zhuan, J. C. Dong, T. M. Cheng, R. T. Li*, Tetrahedron Letters, 2001, 43(3), 461-463 N R + R'CHO + R"NH2 HCl . Y(OTf)3 (10%mmole) N N R' R" N R CHNHR" R' A B