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1、創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶前導物 合成 分離提純測定生物活性 化學預試 傳統(tǒng)方法的局限性： 1)只適合易分離體系； 2)只注重主要合成產物的信息創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶NNH2OHOHOOOOOHOH OOOOOHOH OOHOHOHOOOONHNNHNNHNOOOOHOHNNOOHOHOHNNO

2、OHOHNN創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶OOOO HO HNSOO HOHOHNSOOONS399創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶051015200.00150.00200.00250.00300.0035OD432抑 制 劑 用 量 /g051015200.00100.00150.00200.00250.00300.0035OD432抑 制 劑 用 量 /g創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶圖三圖三 混合物經混合物經TLC的分離結果的分離結果用薄層色譜法可以鑒別出具有抑制能力的化合物。用薄層色譜法可以鑒別出具有抑制能力的化合物。創(chuàng)新答辯-阿卡寧衍生物合成

3、產物中乙酰膽堿酯酶min0246810121416mAU-8-6-4-20 DAD1 B, Sig=500,8 Ref=600,100 (ZNN05051905051902.D) 2.045 2.716 5.907 13.102 14.044 15.057 15.658創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶min051015202530mAU-8-6-4-202 DAD1 B, Sig=500,8 Ref=600,100 (ZNN05051905051905.D) 2.147 2.304 12.648 13.251 19.701 20.131 20.505 20.935創(chuàng)新答辯-阿卡寧衍

4、生物合成產物中乙酰膽堿酯酶RT: 0.00 - 21.110123456789101112131415161718192021Time (min)020000040000060000080000010000001200000140000016000001800000200000022000002400000260000028000003000000320000034000003600000uAU12.164.292.4511.6610.062.773.199.3510.275.342.258.245.4812.887.8513.7014.731.8417.8015.4818.8119.87NL

5、:3.70E6Channel A UV pyridine創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶pyridine #327RT: 12.47AV: 1SB: 7 11.79-12.25NL: 5.54E5T: - c ESI Full ms 150.00-1500.00150200250300350400450500550600650700750800850900m/z050000100000150000200000250000300000350000400000450000500000550000Intensity463.2464.3361.2485.1848.3823.4269.236

6、2.3567.1587.0657.1735.9792.6880.3712.1543.0518.3356.7413.2374.9289.4629.8685.5197.3268.3443.2176.7OOOOOHOHNHN創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶pyridine #311RT: 11.86AV: 1NL: 3.07E5T: - c ESI Full ms 150.00-1500.00150200250300350400450500550600650700750800850900wavelength (nm)020000400006000080000100000120000140

7、000160000180000200000220000240000260000280000300000Intensity461.23361.27462.24362.24393.23878.29876.97640.59677.05483.03341.03550.92898.66591.06816.02500.40768.19309.36701.76578.72440.45249.20174.89306.97224.26OOOOOONHNOOOOOOHNN創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶pyridine #271RT: 10.32AV: 1NL: 1.01E6T: - c ESI Fu

8、ll ms 150.00-1500.00150200250300350400450500550600650700750wavelength (nm)0500001000001500002000002500003000003500004000004500005000005500006000006500007000007500008000008500009000009500001000000Intensity393.25309.22394.28477.14655.46415.31281.26517.04363.05755.11642.51584.48670.76723.04310.37553.25

9、475.00610.57279.35223.19191.01OOHOHOHNNOOHOHHNON創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶pyridine #249RT: 9.48AV: 1NL: 3.35E5T: - c ESI Full ms 150.00-1500.00150200250300350400450500550600650700750800850900wavelength (nm)020000400006000080000100000120000140000160000180000200000220000240000260000280000300000320000Inten

10、sity393.20809.20810.15415.15378.25765.84833.45689.39362.30668.15309.17881.57531.15768.51494.76423.19606.87724.93808.32562.63331.01272.18233.14189.02pyridine #113RT: 4.28AV: 1NL: 4.02E5T: - c ESI Full ms 150.00-1500.00150200250300350400450500550600650700750800850900wavelength (nm)02000040000600008000

11、0100000120000140000160000180000200000220000240000260000280000300000320000340000360000380000400000Intensity409.18443.26547.18391.09525.11339.24779.33453.27737.13513.13718.53352.94819.33253.29566.70639.05508.98311.18654.32843.12884.56202.12230.12創(chuàng)新答辯-阿卡寧衍生物合成產物中乙酰膽堿酯酶pyridine #317RT: 12.09AV: 1NL: 2.6

12、0E5T: - c ESI Full ms 150.00-1500.00150200250300350400450500550600650700750800850900wavelength (nm)020000400006000080000100000120000140000160000180000200000220000240000Intensity461.20361.25483.05405.32777.09406.39583.09565.14745.87706.42822.71393.26496.59643.01584.21438.62562.46869.96333.16697.77730

13、.69788.27542.87322.86271.11183.24249.05pyridine #323RT: 12.32AV: 1NL: 2.81E5T: - c ESI Full ms 150.00-1500.00150200250300350400450500550600650700750800850900wavelength (nm)020000400006000080000100000120000140000160000180000200000220000240000260000280000Intensity361.21463.16461.11877.18464.23844.91692.83497.06363.29405.63545.02809.28662.98589.517

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