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1、习题：,化合物B的分子结构如下，请根据其结构及相应的的2D NMR谱对1H和13C NMR进行归属。,8.16处的信号可被D2O交换: 8.16 ppm (OH),1H NMR谱,H: 8.16; 7.65(d); 7.17; 7.04; 6.20(d); 5.31(t); 5.08; 3.36(d); 2.15(m); 2.10(m); 1.69; 1.66; 1.57,7.65 (d), 6.20 (d): 3-H, 4-H 7.17, 7.04: 5-H, 8-H,1.69 (s), 1.66 (s), 1.57(s): 4-H, 9-H, 10-H,5.31 (t), 5.08: 2-
2、H, 7-H,3.36 (d), 2.15 (m), 2.10 (m): 1-H, 5-H, 6-H,1H-1H COSY谱,7.65 (d), 6.20 (d): H-3, H-4,5.31 (t), 3.36(d): H-2, H-1 5.31 (H-2), 3.36 (H-1),5.08, 2.15, 2.10: H-7, H-6, H-5 5.08 (H-7), 2.15 (H-6), 2.10 (H-5),162.9; 158.8; 153.9; 138.1; 131.6; 126.2; 124.0; 120.9; 111.7; 112.0,13C-1H COSY的DEPT谱,144
3、.7 (C) - 7.65 (H),128.1 (C) - 7.17 (H),103.0 (C) - 7.04 (H),39.6 (C) - 2.10 (H) 5,27.9 (C) - 3.36 (H) 1,26.4 (C) - 2.15 (H) 6,25.7 (C) - 1.66 (H),17.6 (C) - 1.57 (H),16.1 (C) - 1.69 (H),COLOC谱,162.9 (C) - 7.65 (H) 162.9 (C-2),27.9 (C-1) - 7.17 (H) 7.17 (H-5), 128.1 (C-5) 7.04 (H-8), 103.0 (C-8),7.17
4、 (H-5) - 158.8, 153.9, 144.7, 128.1(C) 144.7 (C-4), 7.65 (H-4) 6.20 (H-3), 153.9 (C-8a or C-7),7.04 (H-8) - 126.2, 112.0, 103.0(C) 112.0, 126.2 (C-4a, C-6),6.20 (H-3) - 111.7(C) 111.7 (C-3),COLOC谱,1.66 (H) - 17.6, 25.7, 131.6, 124.0(C) 124.0 (C-7), 131.6 (C-8) 17.6 (C-9), 1.57 (H-9) 25.7 (C-10), 1.6
5、6 (H-10) 1.69 (H-4), 16.1 (C-4) 由于C-6的处于C-9的顺 式，-旁式效应使C-9位 于较高场(17.6), C-10位于较低场(25.7),1.69 (H-4) - 16.1, 138.1 (C) 138.1 (C-3), 120.9(C-2),还没有归属的氢有： 5.31 (t), 5.08: H-2, H-7 比较2和7所处的环境，由于取代基和空间位租效应，2应该比7处于更低场的位置。5.31(H-2), 5.08 (H-7),还没有归属的碳有： 112.0, 126.2: C-4a, C-6 158.8, 153.9: C-7, C-8a,COLOC谱,
6、7.65 (H-4) - 162.9(C-2), 153.9, 144.7 (C-4), 128.1 (C-5) 153.9 (C-8a), 158.8(C-7),6.20 (H-3) - 111.7(C-3), 111.2 111.2 (C-4a), 126.2(C-6),H: 6.20 (d, H-3), 7.65 (d, H-4), 7.17 (H-5), 7.04 (H-8), 3.36 (d, H-1), 5.31 (t, H-2), 1.69 (H-4), 2.10 (m, H-5), 2.15 (m, H-6), 5.08 (H-7), 1.57 (H-9), 1.66 (H-1
7、0), 8.16 (OH),C: 162.9 (C-2), 111.7 (C-3), 144.7 (C-4), 112.0 (C-4a), 128.1 (C-5), 126.2 (C-6), 158.8 (C-7), 103.0 (C-8), 153.9 (C-8a), 27.9 (C-1), 120.9 (C-2), 138.1 (C-3), 16.1 (C-4), 39.6 (C-5), 26.4 (C-6), 124.0 (C-7), 131.6 (C-8), 17.6 (C-9), 25.7 (C-10),Structure Determination with NMR strateg
8、ies & tools in structure elucidation - the structure of Taxol - Pter Sndor Varian Deutschland GmbH,11,From sample to structure,12,Strategy,Information from NMR: # protons, 1H chemical shifts, 1H-1H couplings . 1H spectrum # magnetically nonequivalent carbons . 13C spectrum # NMR-detectable X nuclei
9、(19F, 31P) . X spectrum 1H-13C direct correlation (one-bond) . HSQC (HETCOR) identification if 1H spin systems . TOCSY 1H sequential assignment . COSY 1H-X (13C, 15N, 19F, 31P.) long-range correlation . HMBC stereochemistry, 3D structure . NOESY, ROESY,13,Sample & instrument,Taxol sample: antineopla
10、stic, anti-cancer drug C47H51NO14 Molar Weight: 853.906 Concentration: 5.2 mg in 0.6 ml CDCl3 = 10 mmolar,Instrument: INOVA 500 MHz 4 channels (only 2 used here) 1H,13C,15N triple resonance Probe Pulsed Field Gradient unit Waveform generators,14,1H spectrum of Taxol,1H ppm,Exp. time 1 min,15,13C spe
11、ctrum of Taxol,Exp. time 14 h,13C ppm,CO,aromatic,CH,CH2,CH3,16,Chemical shifts,17,Correlate protons and carbons,2D HSQC: Heteronuclear Single Quantum Coherence,H1,H3,H4,H2a,C4,C1,C2,C3,1H chemical shift,correlate X-1H chemical shifts via one-bond 1J(X,H) couplings,13C chemical shift,H2b,18,2D HSQC
12、spectrum of Taxol,1H ppm,13C ppm,Expansion of the gradient 1H-13C HSQC spectrum 1 scan per increment 256 increments in F1 Exp. time 15 min,19,1H-15N HSQC of Taxol,6.91,15N ppm,1H ppm,gradient 1H-15N HSQC spectrum 8 scans per increment 64 increments in F1 Exp. time 30 min,20,Conclusions from HSQC,Cro
13、ss peaks in 13C HSQC: assigned 26 1H-13C pairs Cross peaks in 15N HSQC: assigned 1 1H-15N pair Positive peaks, integrals 1 & 3 in 1H 1D: 17 CH & 6 CH3 groups Negative peaks, two shifts in 1H dimension: 3 CH2 groups Absent in 13C HSQC but present in 13C 1D: 15 quaternary carbons Absent in 13C HSQC bu
14、t present in 1H 1D: 1 exchangeable NH proton,21,Determine coupling networks,2D TOCSY: TOtal Correlation SpectroscopY,identify protons belonging to the same scalar coupling network / spin system,1H chemical shift,1H chemical shift,22,2D TOCSY spectrum of Taxol,Expansion of the TOCSY spectrum 2 scans
15、per increment 256 increments in F1 Exp. time 32 min,7.3,7.4,7.5,7.6,7.7,7.8,7.9,8.0,8.1,F2,(ppm),7.4,7.5,7.6,7.7,7.8,7.9,8.0,8.1,7.41, 7.35, 7.28,7.67, 7.43, 7.33,8.06, 7.54, 7.44,F1 (ppm),1H ppm,1H ppm,23,Sequential assignment,2D COSY: COrrelation SpectroscopY,correlate scalar coupled protons,24,2D
16、 DQCOSY spectrum of Taxol,O,O,H,H,H,H,H,2.38,4.33,2.47,1.81,4.87,84.41,35.63,72.18,X,X,X,Sequential assignment of spin system Spin system known from TOCSY Geminal pairs known from HSQC,Expansion of the DQ-COSY spectrum 1 scan per increment 640 increments in F1 Exp. time 40 min,1H ppm,1H ppm,25,Subst
17、ructures of Taxol,9 substructures assigned,26,Long range couplings,C,H3C,C,H,H,H,CH3,C5,C3,C4,C1,1H chemical shift,H5,H4,H2b,H1,H2a,13C chemical shift,2D HMBC: Heteronuclear Multiple Bond Coherence,correlate 13C-1H chemical shifts via long-range 2,3J(X,H) couplings,1,2,3,5,C,4,O,C2,27,2D HMBC spectr
18、um of Taxol,Gradient HMBC spectrum 4 scans per increment 1024 increments in F1 optimized for 6 Hz coupling Exp. time 2 h,13C ppm,1H ppm,CO,arom.,CH,CH2,CH3,28,Connect substructures,5.72,167.01,6.91,167.04,8.06,7.67,7.41,167.01,55.04,Expansions of the gradient HMBC spectrum,A,X,O,167.01,127.04,128.72
19、,131.97,133.23,7.67,7.33,7.42,N,H,O,O,O,O,H,H,H,6.91,5.72,3.48,4.72,55.04,73.20,X,167.01,X,X,B,7.41,7.35,128.37,129.03,127.04,137.99,7.28,X,29,Full assignment of Taxol,B,C,A,N,H,O,O,O,O,O,O,O,O,O,O,H,O,O,C,H,3,O,H,O,H,C,H,3,C,H,3,C,H,3,C,H,3,C,H,3,H,H,H,H,H,H,H,H,H,H,H,H,H,H,167.01,127.04,128.72,131
20、.97,133.23,7.67,7.33,7.42,7.41,7.35,7.28,128.37,129.03,127.04,137.99,129.18,130.21,133.71,128.70,167.04,8.06,7.44,7.54,6.91,5.72,3.48,4.72,6.16,2.29,2.22,1.73,1.72,5.61,1.17,1.08,2.17,6.21,3.73,1.62,2.38,4.33,2.47,1.81,4.87,4.23,4.13,2.31,55.04,73.20,172.72,14.83,141.95,133.23,72.41,35.72,79.05,43.1
21、9,171.22,28.84,75.57,26.88,21.83,203.61,9.57,58.65,45.64,81.19,170.35,76.52,22.63,84.41,35.63,72.18,74.98,30,Stereochemistry,31,Proximity in space,H5e,H1a,H1a,H2a,H2a,H5e,H5a,H5a,H3e,H3e,H3a,H3a,4,5,O,1,2,3,H,O,H,H,O,H,H,H,H,Cl,Cl,H,2D NOESY: Nuclear Overhauser Enhanced SpectroscopY,NOE 1/r6 distanc
22、es up to approx. 8 ,detect protons close in space or in chemical exchange,32,2D NOESY spectrum of Taxol,Full NOESY spectrum 4 scans per increment 256 increments in F1 mix time 700 ms Exp. time 2 h 10 min,1H ppm,1H ppm,33,2D NOESY spectrum of Taxol,4.72,3.48,4.72,5.72,7.41,Expansion of the 1H-1H NOESY spectrum,7.41,5.72,6.91,4.72,3.48,34,Stereo structure of Taxol,In the two boxes only the relative configuration is known,35,Thanks!,Dr. Pter Sndor, Application lab Darmstadt,