Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2014 Supporting Information Synthesis of novel 1,2,3-triazolyl derivatives of pregnane, androstane and D-homoandrostane. Tandem Click reaction/cu-catalyzed D-homo rearrangement Yury N. Kotovshchikov, Gennadij V. Latyshev, Nikolay V. Lukashev,* and Irina P. Beletskaya Chemistry Department, M.V. Lomonosov Moscow State University, 1/3 Leninskiye Gory, Moscow, 119991, Russia Fax: +7 (495) 422-32-97 E-mail: nvluk@org.chem.msu.ru
Table of contents Synthetic procedures and characterization data: Compound 17a... 3 Compound 17b... 3 Compound 18a... 3 Compound 19c... 4 Compound S1 (deacetylation of 12a)... 4 Copies of the 1 NMR and 13 C NMR spectra: Compound 4... 6 Compound 6... 7 Compound 8... 8 Compound 9... 9 Compound 10a... 10 Compound 10b... 11 Compound 10c... 12 Compound 10d... 13 Compound 10e... 14 Compound 10f... 15 Compound 10g... 16 Compound 11a... 17 Compound 11b... 18 Compound 11c... 19 Compound 12a... 20 Compound 12b... 21 Compound 12c (+1D NOESY, MBC)... 22 Compound 12d... 28 Compound 13a... 29 Compound 13b... 30 Compound 13c... 31 Compound 13d... 32 Compound 13e... 33 Compound 13f... 34 Compound 16 (+1D NOESY)... 35 Compound 17a... 37 Compound 17b... 38 Compound 18a... 39 Compound 19c... 40 Compound S1... 41 2
3β-hydroxy-16β-chloro-17α-hydroxypregn-5-en-20-one (17a): A solution of 3β-hydroxy-16α,17α-epoxypregn-5-en-20-one (200.0 mg, 0.605 mmol) in a mixture of acetone (12 ml) and conc. Cl (2.0 ml) was stirred under reflux for 6 h. The solution was diluted with C 2 Cl 2 (30 ml), washed with satd. Na 2 CO 3 (30 ml), water (30 ml), dried with anhydrous Na 2 SO 4, and evaporated in vacuum. The residue was purified by column chromatography (eluent: hexanes EtOAc = 2:1). Yield 154.2 mg (69 %). White solid; mp 222 224 C (lit. 1 208 212 C); 1 NMR (400 Mz, CDCl 3 CD 3 OD) δ 5.32 (d, J = 4.6 z, 1, 6- C), 4.12 (m, 1, 16-CCl), 3.89 (br s, 2, O), 3.45 (m, 1, 3-CO), 2.60 2.52 (m, 1), 2.30 (s, 3, 21-C 3 ), 2.29 2.16 (m, 2), 2.00 1.91 (m, 1), 1.87 1.76 (m, 2), 1.69 1.41 (m, 9), 1.19 (s, 3, 18-C 3 ), 1.10 0.90 (m, 2), 1.01 (s, 3, 19-C 3 ); 13 C NMR (100.6 Mz, CDCl 3 CD 3 OD) δ 206.4 [C(20)=O], 140.8 (5-C), 120.7 (6-C), 89.5 (17-C), 71.0 (3-CO), 62.6 (16-CCl), 49.4, 48.9, 46.6 (quat.), 41.6, 37.7, 37.0, 36.3 (quat.), 31.5, 30.9 (), 30.8, 27.7, 19.7, 19.1, 14.8. 16β-(phenylthio)-3β,17α-dihydroxypregn-5-en-20-one (17b): A mixture of 3β-hydroxy-16α,17α-epoxypregn-5-en-20-one (220.0 mg, 0.666 mmol), thiophenol (0.20 ml, 1.94 mmol) and anhydrous K 2 CO 3 (84.0 mg, 0.608 mmol) in acetone (2.0 ml) was stirred under reflux for 2 days. The solution was diluted with C 2 Cl 2 (25 ml), washed with satd. Na 2 CO 3 (25 ml), water (25 ml), dried with anhydrous Na 2 SO 4, and evaporated in vacuum. The residue was purified by column chromatography (eluent: C 2 Cl 2 MeO = 100:1). Yield 255.0 mg (87 %). White solid; mp 175 177 C (lit. 2 178 180 C); 1 NMR (400 Mz, CDCl 3 ) δ 7.26 7.20 [m, 2, 3,5-C(Ph)], 7.19 7.15 [m, 2, 2,6-C(Ph)], 7.14 7.09 [m, 1, 4-C(Ph)], 5.33 (d, J = 5.1 z, 1, 6-C), 3.70 (t, J = 8.6 z, 1, 16-CSPh), 3.51 (tt, J = 11.3, 4.6 z, 1, 3- CO), 2.44 (ddd, J = 14.7, 8.4, 6.3 z, 1), 2.33 (s, 3, 21-C 3 ), 2.32 2.17 (m, 2), 2.05 1.94 (m, 1), 1.87 1.37 (m, 11), 1.29 1.22 (m, 2), 1.11 0.94 (m, 2), 1.07 (s, 3, 18-C 3 ), 1.01 (s, 3, 19-C 3 ); 13 C NMR (100.6 Mz, CDCl 3 ) δ 209.9 [C(20)=O], 140.7 (5-C), 137.5 [1- C(Ph)], 129.0 [, C(Ph)], 127.7 [, C(Ph)], 125.7 [4-C(Ph)], 121.1 (6-C), 90.8 (17-C), 71.6 (3-CO), 53.6 (16-CSPh), 49.6, 49.4, 49.2 (quat.), 42.2, 37.2, 36.5 (quat.), 35.5, 31.9, 31.5, 31.2, 30.6, 30.0, 20.1, 19.4, 16.2. 3β,16β-diacetoxy-17α-hydroxypregn-5-en-20-one (18a): A solution of 3β-acetoxy-16α,17α-epoxypregn-5-en-20-one (360.0 mg, 0.966 mmol) in a mixture of acetic acid (13.4 ml) and conc. 2 SO 4 (0.67 ml) was stirred at rt for 6 h. The solution was diluted with C 2 Cl 2 (50 ml), washed with water (50 ml), satd. Na 2 CO 3 (2 50 ml), dried with anhydrous Na 2 SO 4, and evaporated in vacuum. The residue was purified by 3
column chromatography (eluent: hexanes EtOAc = 4:1). Yield 140.6 mg (34 %). White solid; mp 170 172 C (lit. 3 168 170 C); 1 NMR (400 Mz, CDCl 3 ) δ 5.36 (d, J = 4.2 z, 1, 6- C), 4.81 (t, J = 7.3 z, 1, 16-COAc), 4.59 (m, 1, 3-COAc), 3.42 (s, 1, O), 2.37 2.36 (m, 3), 2.22 (s, 3, 21-C 3 ), 2.05 [s, 3, OC(O)C 3 ], 2.02 [s, 3, OC(O)C 3 ], 2.02 1.94 (m, 1), 1.90 1.81 (m, 2), 1.75 1.35 (m, 9), 1.19 0.96 (m, 2), 1.02 (s, 3, 19-C 3 ), 0.93 (s, 3, 18-C 3 ); 13 C NMR (100.6 Mz, CDCl 3 ) δ 208.7 [C(20)=O], 171.2 [OC(O)C 3 ], 170.5 [OC(O)C 3 ], 139.7 (5-C), 122.0 (6-C), 88.0 (17-C), 83.4 (16-COAc), 73.7 (3-COAc), 49.4, 47.7, 47.3 (quat.), 38.0, 36.9, 36.6 (quat.), 33.1, 31.8, 31.1, 30.7, 29.1, 27.7, 21.4, 21.2, 20.2, 19.3, 15.1. 16β-thiocyanato-17α-hydroxypregn-4-ene-3,20-dione (19c): A mixture of 16α,17α-epoxypregn-4-ene-3,20-dione (227.9 mg, 0.694 mmol) and KSCN (900 mg, 9.26 mmol) in acetic acid (5.0 ml) was stirred at 100 C for 5 h. The mixture was diluted with C 2 Cl 2 (30 ml), washed with water (30 ml), satd. Na 2 CO 3 (2 30 ml), dried with anhydrous Na 2 SO 4, and evaporated in vacuum. The residue was purified by column chromatography (eluent: C 2 Cl 2 MeO = 50:1). Yield 102.0 mg (38 %). White solid; mp 236 238 C (dec.) (lit. 4 237 239 C); 1 NMR (400 Mz, CDCl 3 CD 3 OD) δ 5.68 (s, 1, 4-C), 3.59 3.52 (m, 1, 16-CSCN), 2.78 (br s, 1, O), 2.63 2.55 (m, 2), 2.43 2.20 (m, 3), 2.15 (s, 3, 21-C 3 ), 2.02 1.55 (m, 8), 1.47 1.30 (m, 2), 1.21 0.90 (m, 2), 1.13 (s, 3, 19- C 3 ), 0.70 (s, 3, 18-C 3 ); 13 C NMR (100.6 Mz, CDCl 3 CD 3 OD) δ 211.7 [C(20)=O], 200.3 [C(3)=O], 171.7 (5-C), 123.6 (4-C), 115.4 (SCN), 88.7 (17-C), 53.8, 52.8, 48.3, 48.1 (quat.), 38.4 (quat.), 37.4, 35.3, 35.0, 33.6, 32.5, 31.7, 30.9, 27.4, 20.4, 17.1, 15.1. Deacetylation of 12a: 3β,17α-dihydroxy-16β-(4-phenyl-1-1,2,3-triazol-1-yl)-17β-methyl-D-homoandrost-5-en- 17a-one (S1): A suspension of 12a (15.9 mg, 30.7 µmol) and K 2 CO 3 (8.6 mg, 62 µmol) in the mixture of MeO (1 ml), TF (0.3 ml) and water (0.1 ml) was heated under reflux for 20 min. The solution was diluted with C 2 Cl 2 (20 ml), washed with water (2 20 ml), dried with anhydrous Na 2 SO 4, and evaporated in vacuum. The residue was subjected to column chromatography (eluent: C 2 Cl 2 MeO = 30:1) to afford the pure product. Yield 12.9 mg (88 %). White solid; mp 291 293 C; 1 NMR (400 Mz, CD 2 Cl 2 CD 3 OD) δ 7.97 [s, 1, C(triazole)], 7.78 7.73 [m, 2, 2,6-C(Ph)], 7.39 7.32 [m, 2, 3,5-C(Ph)], 7.26 [tt, J = 7.4, 1.7 z, 1, 4-C(Ph)], 5.27 (m, 1, 6-C), 4.39 (dd, J = 12.8, 4.3 z, 1, 16-C), 3.37 (tt, J = 11.1, 4.7 z, 1, 3-CO), 2.54 (q, J = 13.3 z, 1, 15β-C), 2.45 2.33 (m, 3, 15α-C + 2 4
O), 2.26 2.08 (m, 3), 1.93 (m, 1), 1.84 1.62 (m, 4), 1.59 1.34 (m, 4), 1.26 (ddd, J = 13.0, 10.5, 2.8 z, 1), 1.17 (s, 3, 17-CC3), 1.05 0.91 (m, 2), 1.02 (s, 3, 18-C3), 0.97 (s, 3, 19-C3); 13 C NMR (100.6 Mz, CD 2 Cl 2 CD 3 OD) δ 215.7 [C(17a)=O], 147.5 [C(triazole)], 141.5 (5-C), 131.2 [1-C(Ph)], 129.4 [, C(Ph)], 128.7 [4-C(Ph)], 126.2 [, C(Ph)], 122.3 [6-C or C(triazole)], 120.9 [6-C or C(triazole)], 79.0 (17-CO), 71.7 (3- CO), 69.5 (16-C), 49.7, 48.5, 47.4 (quat.), 42.3, 37.41, 37.37 (quat.), 33.4, 32.2, 31.9, 31.4, 26.3, 23.3, 19.9, 19.7, 16.4; RMS (MALDI-TOF) calcd for C 29 38 N 3 O 3 [M+]+ 476.2913; found 476.2911. 1. V. Schwarz and K. Syhora, Collect. Czech. Chem. Commun., 1963, 28, 637. 2. N. Bischofberger and K. A. M. Walker, J. Org. Chem., 1985, 50, 3604. 3. A. A. Akhrem, V. A. Dubrovskii, A. V. Kamernitskii and A. V. Skorova, Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.), 1969, 18, 2620. 4. T. Komeno, Chem. Pharm. Bull., 1960, 8, 680. 5
7.25 5.72 3.50 3.53 3.22 3.25 2.40 2.38 2.37 2.29 2.35 2.35 2.27 2.03 2.02 1.69 2.01 1.69 1.67 1.66 1.65 1.62 1.61 1.60 1.46 1.43 1.38 1.14 1.17 1.18 0.92 0.93 0.89 0.05 - MD 0.92 1.01 1.00 4.08 5.265.29 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 199.43 170.77 83.15 45.71 38.57 123.94 58.25 50.73 53.61 31.63 31.74 34.67 35.68 36.25 14.06 17.33 23.47 20.56 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 6
1.18 4.45 4.50 4.22 3.92 3.97 2.70 2.64 2.67 2.41 2.44 2.40 2.37 2.32 2.29 2.01 1.69 1.79 1.85 1.88 1.53 1.42 1.59 1.62 1.24 1.381.40 5.69 7.48 0.95 0.97 1.10 0.65 0.05-MDS 1.00 1.171.02 1.19 1.05 4.33 1.12 2.92 3.16 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 DMSO-d6 206.87 198.78 170.72 88.79 47.09 37.95 123.14 49.73 52.62 55.47 32.20 33.34 35.01 31.43 29.93 23.01 16.77 20.06 14.31 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 7
7.26 5.37 5.36 4.58 4.17 3.54 3.53 3.51 3.50 2.38 2.36 2.34 2.33 2.31 2.17 1.96 2.02 1.88 1.65 1.53 1.61 1.85 1.57 1.59 1.40 1.24 1.15 1.10 1.01 0.05-MD 1.00 0.99 0.97 1.00 3.153.43 3.08 3.31 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 215.33 19.19 170.44 139.61 121.38 79.67 69.60 73.47 48.84 46.34 47.17 37.73 36.49 32.62 27.54 27.10 21.35 22.73 15.77 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 8
1.02 7.26 5.37 4.58 3.97 3.95 3.93 3.62 2.30 2.32 2.38 2.02 1.86 1.83 1.64 1.62 1.40 1.46 1.48 1.37 1.12 0.05-MDS 1.00 0.99 0.94 0.95 5.82 3.23 5.80 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 208.29 170.55 139.70 121.95 89.15 73.74 69.49 49.40 47.61 48.59 37.99 36.90 33.10 31.73 29.50 30.50 27.64 36.57 21.38 19.26 19.90 15.26 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 9
Et2O 1.21 0.94 Cl2 4.46 4.43 4.23 4.27 Et2O MeO 3.64 3.44 3.43 2O 3.28 DMSO 2.45 2.56 4.63 7.82 7.87 5.66 5.44 5.00 2.43 2.41 2.29 2.03 2.02 1.89 1.86 1.70 1.72 1.69 1.60 1.65 1.62 1.31 1.34 1.58 1.14 1.15 0.97 0.05 - M 0.05 1.00 1.00 0.97 3.151.071.05 4.27 1.08 3.063.33 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 122.31 48.96 52.14 54.56 54.91 35.00 31.30 29.52 30.25 DMSO-d6 146.58 197.36 169.64 44.82 22.09 19.19 15.99 13.10 37.22 80.72 122.88 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 10
O 7.70 10b O N N N 5.58 O 4.80 4.62 4.37 4.34 4.12 4.15 MeO 3.80 MeO aqua 3.18 3.06 DMSO-d6 1.64 1.67 2.49 2.38 2.34 2.28 2.20 2.02 1.99 1.83 1.69 1.33 1.44 1.46 1.25 1.30 1.07 1.19 1.03 1.00 0.88 0.99 0.95 1.00.991.00 1.03 4.22 1.15 6.582.82 2.96 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 123.20 30.38 CCl4 55.49 30.74 DMSO-d6 33.36 35.99 32.08 23.02 20.14 45.69 16.90 14.04 38.03 52.87 49.61 67.06 121.42 81.36 196.77 169.48 155.23 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 11
7.58 7.31 5.72 4.44 4.30 4.33 4.40 Et2O 2.71 2.67 2.69 2.41 2.37 2.35 2.34 2.30 1.73 1.72 1.70 1.40 1.61 1.63 1.65 1.38 1.24 1.33 1.35 1.17 1.19 1.20 1.00 0.89 0.91 0.05 - MD 0.05 1.00 1.00 1.03 2.10 4.35 1.19 2.993.37 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 199.34 170.90 122.94 123.76 147.83 82.60 56.19 50.21 53.50 46.00 38.46 35.52 36.24 25.18 30.81 31.33 32.57 23.39 22.12 20.40 17.21 13.68 14.04 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 12
O 7.80 10d 7.28 O N N N 5.73 NEt 2 Cl2 5.29 4.45 4.31 4.35 4.41 3.84 3.20 2.62 2.57 2.60 2.39 2.58 2.36 2.30 2.35 1.88 1.72 1.70 1.69 1.42 1.65 1.33 1.62 1.27 1.24 1.20 0.83 0.95 0.97 0.98 1.10 0.05 - MDS 0.05 1.07 1.00 2.27 2.47 0.79 4.524.64 1.14 7.00 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0-0.5 199.32 170.69 143.61 123.94 125.25 82.74 56.35 53.58 50.34 47.40 46.10 46.64 35.64 36.34 32.62 30.95 31.53 23.50 20.49 38.55 17.31 14.09 11.43 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 13
O 8.19 7.80 7.82 10e 7.62 7.40 7.29 O N N N 5.69 Cl2 5.37 4.56 4.31 4.34 4.49 aqua 3.01 DMSO-d6 0.97 2.56 2.44 2.38 2.30 2.05 2.02 1.74 1.71 1.66 1.53 1.44 1.32 1.37 1.07 1.21 1.00 0.05 - MDS 0.05 1.03 2.08 2.09 1.00 2.07 1.05 4.221.12 6.37 2.983.56 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0-0.5 126.94 127.90 122.84 124.54 121.37 55.63 52.67 49.49 DMSO-d6 45.36 35.51 34.73 33.04 31.80 30.71 30.08 22.59 19.68 16.47 13.53 37.70 81.31 198.09 170.12 145.93 130.14 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 14
8.27 8.25 8.22 7.98 8.01 7.26 5.72 4.58 4.37 4.41 4.54 MeO 3.47 2.60 2.41 2.40 2.38 2.36 2.04 2.35 1.78 1.76 1.75 1.73 1.52 1.69 1.72 1.68 1.36 1.39 1.20 0.99 1.01 0.98 0.96 0.05 - MDS 0.05 3.112.09 1.00 1.05 1.034.23 1.17 3.08 5.29 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0-0.5 126.00 123.97 124.24 123.52 199.40 50.30 53.58 56.45 170.71 147.12 145.23 46.12 36.37 35.65 33.85 33.25 32.61 31.48 30.94 23.47 17.32 20.50 14.05 38.55 82.92 137.05 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 15
7.68 7.26 5.73 4.07 Cl2 5.28 4.32 4.77 4.44 4.73 4.40 4.34 2.91 2.41 2.35 2.03 2.00 1.84 1.47 1.62 1.72 1.68 1.65 1.43 1.35 1.19 1.05 0.94 1.00 0.05-MDS 1.05 1.00 2.14 4.435.49 0.99 4.36 1.18 2.96 3.07 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0-0. 5C 199.37 170.65 146.42 82.96 75.85 46.10 38.57 124.00 121.16 66.74 50.33 53.60 56.27 36.37 33.89 33.26 32.66 31.54 30.96 23.52 20.52 17.34 14.10 68.86 69.80 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 16
7.82 7.89 Cl2 7.43 7.32 7.39 7.41 5.71 5.76 2.68 1.00 5.36 5.40 5.31 2.41 2.29 1.66 0.05 - MDS 4.57 0.82 0.05 1.18 2.03 1.74 1.86 1.46 0.66 3.02 3.23 2.000.98 1.16 1.08 2.98 2.89 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0-0.5 DMSO-d6 203.98 199.15 32.43 33.59 35.30 31.67 30.32 23.27 20.37 14.64 17.02 170.89 147.13 89.30 47.65 38.19 50.06 52.84 56.61 127.79 128.46 125.36 123.45 121.44 130.11 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 17
7.29 7.32 5.69 5.72 5.74 5.32 5.27 4.62 Et2O 2.72 2.70 2.41 2.68 2.37 2.36 2.35 2.02 1.88 1.79 1.85 1.86 1.69 1.66 1.42 1.61 1.64 1.63 1.40 1.38 1.33 1.34 1.36 1.19 1.12 1.17 1.18 1.00 0.93 0.90 0.91 0.66 0.05 - MDS 0.90 2.03 1.00 0.78 3.05 4.39 2.16 3.343.12 2.91 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 2С 35.57 204.14 199.77 171.51 148.10 122.63 123.69 89.80 56.78 48.10 50.36 53.16 38.49 33.80 30.57 31.31 25.14 22.18 23.52 20.63 14.92 17.28 13.73 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 18
0.63 1.01 1.19 4.22 2.66 2.63 2.44 2.41 2.26 2.30 2.05 2.03 1.88 1.83 1.70 1.86 1.63 1.32 1.60 1.30 1.29 1.24 4.70 7.65 5.64 5.68 5.28 5.33 0.84 MDS 1.06 2.00 1.21 1.92 1.17 1.06 2.84 2.99 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0-0.5 DMSO-d6 2С 203.51 198.06 170.17 147.44 122.69 122.88 88.42 55.73 46.82 49.35 52.21 54.99 37.53 31.74 32.93 34.60 31.04 29.61 22.59 19.70 16.37 13.91 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 19
7.86 7.99 7.85 7.43 7.33 7.25 7.31 7.39 7.41 Cl2 5.36 5.28 4.59 4.43 4.42 4.40 4.31 2.70 2.67 2.63 2.49 2.53 2.30 2.33 1.90 2.02 1.74 1.87 1.72 1.71 1.50 1.31 1.23 1.08 1.05 1.12 0.86 MDS 0.05 1.82 1.91 0.96 0.980.96 1.03 3.013.77 3.65 6.24 215.09 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 170.51 147.19 139.53 130.64 125.73 128.05 128.77 121.45 78.57 73.50 68.86 46.72 47.96 48.91 19.25 37.74 36.55 32.72 31.60 30.76 27.58 25.55 21.40 22.87 15.92 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 20
1.22 1.89 1.87 1.67 1.65 1.63 1.49 1.33 1.38 1.36 1.13 0.94 1.04 0.90 0.92 1.03 2.02 7.48 7.26 5.35 5.35 4.29 4.59 4.58 4.34 4.33 4.31 2.73 2.70 2.72 2.62 2.59 2.47 2.34 2.33 2.29 MDS 0.05 0.96 1.00 1.021.97 1.95 3.064.03 2.81 6.59 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 215.19 77.00 48.88 46.63 47.94 36.51 37.69 170.44 147.75 122.41 78.58 30.71 31.55 32.69 27.53 25.52 22.80 19.18 22.23 15.83 13.75 68.49 73.45 121.44 139.47 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 21
7.77 7.26 5.36 5.29 5.35 4.59 4.80 4.58 4.40 4.36 4.38 4.35 3.00 2.65 2.62 2.55 2.59 2.46 2.45 2.34 2.32 2.29 1.90 2.02 1.89 1.72 1.87 1.71 1.57 1.49 1.22 1.13 0.99 1.02 1.04 MDS 0.05 0.89 0.99 1.851.03 1.90 0.76 0.89 2.923.92 3.14 7.00 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 2С 147.05 214.94 170.49 123.51 139.56 21.35 15.90 19.22 121.39 78.52 68.80 73.48 56.40 48.90 46.70 47.94 37.72 32.71 36.53 30.73 27.55 25.62 22.83 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 22
7.79 7.33 5.35 4.77 4.58 4.73 4.57 4.56 4.45 4.44 4.42 4.41 3.08 2.59 2.55 2.42 2.41 2.39 2.35 2.33 2.29 2.32 1.90 2.02 1.86 1.87 1.72 1.70 1.48 1.32 1.21 1.12 1.04 1.01 1.03 1.00 0.86 0.05-M 0.90 0.92 2.030.96 1.50 1.003.52 3.101.71 3.571.01 6.39 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 170.60 146.99 139.34 73.47 46.63 78.33 47.59 48.72 55.65 37.53 36.34 36.64 31.39 30.54 15.80 19.02 21.16 22.55 27.36 25.47 68.48 214.75 121.28 123.70 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 23
2.59 2.56 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 2.55 2.59 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 24
MBC for 12c 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 25
MBC for 12c 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 15 20 25 30 35 40 45 50 55 60 65 70 75 80 26
MBC for 12c 27
0.86 0.85 0.84 1.24 1.16 1.17 1.87 1.71 1.60 1.59 1.51 1.49 1.26 1.22 1.04 1.03 7.85 7.26 5.35 4.61 4.58 4.40 4.39 4.00 3.96 3.90 3.94 2.68 2.60 2.67 2.57 2.67 2.46 2.33 2.02 0.05-hmds 0.91 1.00 1.06 1.11 2.09 4.94 3.143.93 2.66 5.78 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 46.52 19.19 214.91 170.44 142.21 139.48 78.43 125.16 15.86 11.14 37.68 36.49 32.66 27.52 30.70 25.53 21.34 22.82 121.40 73.45 68.67 48.84 77.00 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 28
O AcO 7.79 7.80 7.82 13a 7.42 7.39 7.41 7.34 7.30 7.32 7.25 O N N N 5.40 5.38 4.99 4.94 4.97 4.61 4.50 2.66 2.63 2.60 2.57 2.50 2.48 2.10 2.34 2.06 1.88 2.03 1.86 1.78 1.64 1.67 1.51 1.30 1.27 1.14 1.06 0.05 - M 0.05 2.83 1.97 1.00 0.96 1.00 0.992.094.04 3.28 3.38 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 125.70 208.80 170.53 147.95 139.77 130.16 128.34 128.84 121.86 120.93 90.36 71.29 73.70 49.26 48.69 36.61 36.88 37.99 31.93 31.72 27.93 27.65 21.40 20.12 19.30 15.87 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 29
O AcO 7.25 7.42 13b O N N N 5.38 4.94 4.90 4.92 4.60 2.72 2.61 2.47 2.59 2.69 2.71 2.31 2.33 2.081.80 1.85 2.03 1.62 1.74 1.65 1.05 1.10 1.49 1.39 1.37 1.33 1.35 1.15 1.24 0.93 0.90 0.91 MDS 0.05 0.92 1.00 0.91 1.23 1.97 4.29 4.892.41 3.60 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 77.00 73.64 70.96 48.35 49.17 37.90 36.51 36.79 31.85 28.14 30.71 30.91 25.13 27.55 22.16 20.13 15.56 19.20 13.71 89.74 121.84 122.29 139.65 148.13 209.01 170.48 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 30
O O N N N O 2.03 AcO 1.04 13c 7.73 7.25 5.37 4.98 4.60 4.74 3.84 2.33 0.98 2.42 1.82 1.64 1.24 MDS 0.05 1.17 1.48 1.001.701.51 1.77 5.97 6.075.07 4.69 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 147.75 129.07 89.11 71.50 55.84 209.93 170.60 139.72 121.83 73.70 48.18 49.16 37.94 36.82 31.89 28.79 31.07 27.58 21.36 19.23 15.36 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 31
1.78 1.70 1.73 1.65 1.44 1.63 1.34 1.23 1.15 1.19 1.21 1.04 0.92 0.86 0.98 0.83 0.84 7.93 7.26 5.39 5.38 4.95 4.97 5.12 4.60 4.59 4.58 4.04 4.00 3.95 3.98 3.04 2.80 2.79 2.77 2.55 2.52 2.40 2.31 2.33 2.34 1.99 2.03 0.61 1.85 0.05-hmds 0.93 1.02 1.00 1.00 1.90 3.283.91 6.67 7.353.17 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 36.54 209.27 170.45 139.69 141.35 125.72 121.87 89.31 71.24 73.69 48.43 49.20 46.47 36.84 37.95 31.91 31.10 27.61 28.78 21.32 19.23 15.32 10.61 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 32
MDS 10.70 7.88 7.37 7.16 7.25 6.96 6.98 5.39 5.00 4.61 4.24 2.53 2.16 2.342.51 1.61 1.36 0.05 1.76 2.04 1.08 1.06 0.76 0.96 0.980.93 1.001.001.03 0.96 2.23 4.284.84 1.11 6.31 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 208.27 170.74 154.32 146.25 139.73 129.44 124.13 125.38 120.53 121.74 118.95 115.02 89.92 15.71 71.70 73.75 49.17 48.52 37.93 31.75 30.91 30.84 27.59 36.55 28.31 19.24 20.20 21.40 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 33
5.25 0.88 1.04 7.99 8.01 7.75 7.29 7.01 6.99 1.93 2.03 MDS 0.05 5.38 5.37 4.99 4.94 4.96 4.58 CD3OD 2.91 2.46 2.42 2.18 2.32 2.34 1.81 1.89 1.86 1.71 1.50 1.69 1.41 1.24 1.960.95 2.00 1.981.00 1.01 2.93 2.134.04 3.57 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0-0. 131.97 114.28 209.49 170.84 169.03 161.98 88.90 71.53 73.79 61.78 49.09 48.13 37.84 36.46 36.72 31.91 28.60 30.95 27.51 21.27 20.27 19.15 15.47 139.63 142.84 121.72 123.74 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 34
O AcO 7.44 7.26 16 O N N N 5.34 5.33 4.59 4.58 4.57 4.35 4.32 4.32 3.36 3.06 2.69 2.71 2.73 2.15 2.31 2.04 1.86 2.02 1.66 1.64 1.62 1.52 1.49 1.37 1.36 1.11 1.24 1.02 0.92 0.86 0.89 0.05 - MD 1.01 0.99 1.000.85 0.89 1.61 1.98 2.003.16 2.29 8.24 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 170.58 147.29 139.62 76.22 38.23 121.56 121.64 84.04 73.67 67.54 49.32 48.62 11.26 13.80 37.22 37.79 36.60 31.80 31.48 30.24 27.60 26.50 25.20 17.42 19.24 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 35
7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 4.30 4.27 3.32 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 36
1.19 1.01 2.30 CD3OD 3.47 3.45 3.44 3.43 3.35 3.89 7.36 5.32 5.33 4.14 4.13 4.12 4.11 2.56 2.58 2.20 2.24 2.04 1.86 1.82 1.56 1.44 1.47 1.50 1.61 1.63 1.24 1.05 0.05-MD 1.00 0.992.83 1.00 1.02 5.22 2.349.70 3.175.92 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 48.94 206.37 140.76 120.73 89.51 30.90 70.98 62.65 49.43 46.59 37.68 41.57 36.30 36.97 31.50 27.72 14.80 19.07 19.69 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 37
7.23 7.25 7.21 7.18 7.13 7.16 7.18 7.12 5.34 5.32 2.33 3.72 3.68 3.70 3.51 2.43 2.28 2.27 2.01 1.84 1.81 1.65 1.58 1.60 1.62 1.57 1.50 1.48 1.47 1.07 0.99 1.01 0.98 0.05-M 3.93 0.91 1.001.06 2.10 1.32 1.777.24 1.166.60 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 209.94 137.51 140.73 125.74 121.11 127.72 129.01 90.85 71.58 30.01 53.57 49.55 49.42 49.24 42.15 37.16 35.46 36.50 31.86 31.22 20.10 16.16 19.36 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 38
Cl2 0.05-MDS 0.05 0.93 1.43 1.45 1.61 1.84 1.70 3.42 2.32 1.02 2.22 7.26 5.37 5.29 5.36 4.79 4.81 4.83 4.59 2.05 2.02 1.42 1.24 1.02 1.00 1.02 0.98 3.16 7.39 9.94 3.98 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 208.71 170.48 171.20 139.69 122.02 83.37 87.97 73.75 49.42 47.26 47.67 38.00 36.59 36.89 31.81 31.10 30.74 31.10 29.05 21.38 27.66 20.17 19.27 15.10 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 39
0.70 CD3OD 1.13 1.97 1.94 1.85 1.69 1.72 1.35 1.40 1.15 2.15 5.68 7.24 3.55 3.57 3.36 2.78 2.59 2.60 2.26 0.96 0.99 0.05-M 0.05 1.00 1.03 3.891.09 3.283.01 2.185.72 2.234.00 1.752.85 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 CD3OD 211.73 200.29 171.69 123.60 115.40 88.66 48.30 52.80 53.78 37.36 38.43 31.67 35.05 30.93 20.37 17.12 48.05 27.39 15.12 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 40
7.97 7.76 7.75 7.37 7.28 7.34 7.36 7.26 CDl2 5.28 5.27 4.41 4.40 4.38 4.37 CD3OD 3.37 2.55 2.52 2.41 2.41 2.23 2.39 2.20 1.95 2.19 1.92 1.82 1.79 1.72 1.68 1.42 1.39 1.26 1.18 1.17 0.95 0.97 1.02 TMS 1.01.98 2.03 1.13 0.99 1.07 6.93 3.541.42 4.375.19 8.55 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 CDl2 120.95 122.25 79.02 69.51 71.73 CD3OD 49.68 47.41 42.32 37.37 126.19 215.70 147.46 141.49 128.67 129.39 131.20 37.41 31.39 32.20 33.39 26.25 23.28 19.67 16.43 216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 41