Total Synthesis of Lobatoside E, a Potent Antitumor Cyclic Triterpene Saponin Chunsheng Zhu, Pingping Tang, and Biao Yu* State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of rganic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China E-mail: byu@mail.sioc.ac.cn Supporting Information Experimental details, characterization data, and NMR spectra for new compounds.
BnBr, K 2 C 3,Bu 4 NBr C 2 Cl 2 / 2, 50 o C,94% Bn 8 S1 To a suspension of oleanolic acid 8 (4.56 g, 10 mmol) in C 2 Cl 2 (150 ml) were added a solution of K 2 C 3 (2.76 g, 20 mmol) in water (50 ml), Bu 4 NBr (2.58g, 8 mmol) and BnBr (1.8 ml, 15 mmol). The mixture was stirred at 50 o C for 6 h and was quenched by addition of aqueous Cl (1 N), and followed by dilution with C 2 Cl 2. The organic layerl was separated, washed ( 2 and then brine) and dried over Na 2 S 4. Concentration in vacuo and purification by silica gel flash column chromatography (petroleum ether/etac: 8/1) furnished S1 (5.11 g, 94%) as a white solid: 1 NMR (300 Mz, CDCl 3 ) δ 7.34 (m, 5), 5.30 (s-like, 1), 5.07 (AB, 2), 3.21 (dd, J = 4.8, 9.9 z, 1), 2.91 (dd, J = 3.9, 13.2 z, 1), 1.13, 0.98, 0.92, 0.90, 0.88, 0.78, 0.61 (s, each 3). Bn Jones reagent, acetone 0 o Ctort,92% Bn S1 S2 Benzyl oleanolate S1 (14.40 g, 26.32 mmol) was dissolved in acetone (250 ml), and Jones reagent (14 ml) was added dropwise at 0 o C. After stirring at 0 o C for 30 min, the reaction mixture was quenched by addition of i-pr, followed by concentration in vacuo to remove acetone. The residue was dissolved in C 2 Cl 2, washed ( 2 and then brine), and dried over Na 2 S 4. Concentration in vacuo and purification by silica gel flash column chromatography (petroleum ether/c 2 Cl 2 : 1/1 to 1/2) furnished S2 (13.28 g, 92%) as a white solid: [α] 25 D = 76.2 (c 1.12, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.34 (m, 5), 5.29 (s-like, 1), 5.08 (AB, 2), 2.91 (dd, J = 4.5, 14.1 z, 1), 2.54 (ddd, J = 6.9, 10.5, 15.6 z, 1), 2.35 (ddd, J = 3.3, 6.6, 15.6 z, 1), 1.13, 1.08, 1.04, 1.01, 0.92, 0.90, 0.65 (s, each 3); ESI-MS m/z 545 [M+] +, 583 [M+K] +. Anal. Calcd for C 37 53 3 : C, 81.57;, 9.62. Found: C, 81.44;, 9.78. S1
Bn 2 N Cl, NaAc, Me/C 2 Cl 2, reflux, 95% Bn N S2 9 Compound S2 (92 mg, 0.17 mmol) was dissolved in Me/C 2 Cl 2 (6 ml/3 ml), and N 2 Cl (18 mg, 0.25 mmol) and NaAc (42 mg, 0.51 mmol) was added at rt. After stirring overnight at reflux, the reaction mixture was diluted by addition of brine, then extracted with C 2 Cl 2. The extract was dried over Na 2 S 4, followed by filtration, concentration in vacuo, and purification by silica gel flash column chromatography (petroleum ether/c 2 Cl 2 : 1/1 to 1/2) to give 9 (96 mg, 95%) as a white foam: [α] 25 D = 17.7 (c 1.12, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.33 (m, 5), 5.29 (s, 1), 5.07 (AB, 2), 3.07 (ddd, J = 3.0, 5.1, 15.3 z, 1), 2.90 (dd, J = 3.6, 13.8 z, 1), 2.14 (m, 1), 1.14, 1.10, 1.04, 0.99, 0.91, 0.89, 0.63 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 177.5, 166.9, 143.7, 136.5, 128.4, 128.3, 128.2, 128.0, 127.9, 122.4, 66.0, 55.9, 47.2, 46.8, 45.8, 41.8, 41.7, 41.5, 40.4, 39.4, 38.5, 37.1, 33.9, 33.1, 32.5, 32.4, 30.7, 27.6, 27.2, 25.8, 23.7, 23.5, 23.3, 23.1, 19.1, 17.1, 16.9, 14.9; RMS (ESI) m/z calcd for C 37 54 N 3 560.4098 [M+] +, found 560.4118. N 9 Bn 1) Na 2 PdCl 4,NaAc,Ac,rt 2) Ac 2, Et 3 N, DMAP,C 2 Cl 2,rt 3) Py, TF; Pb(Ac) 4,Ac, -78 o Ac Ctort;NaB 4, aq.na, rt, 72% N To a solution of benzyl 3-hydroxyiminoolean-12-en-28-oate 9 (1.00 g, 1.67 mmol) in Ac (90 ml) were added NaAc (150 mg, 1.83 mmol) and Na 2 PdCl 4 (562 mg, 1.87 mmol). The solution was stirred for 72 h at rt, and ice water (150 ml) was added to give a yellow precipitate. The palladium complex was filtered and dried in vacuo for 24 h. To a solution of this yellow solid in dry C 2 Cl 2 (15 ml) were added DMAP (19 mg, 0.15 mmol), Et 3 N (0.33 ml, 2.36 mmol), and Ac 2 (0.21 ml, 2.21 mmol). The reaction mixture was stirred at rt for 45 min, washed with water and brine, dried over anhydrous Na 2 S 4, filtered, and evaporated at reduced pressure. The crude product was dissolved in dry TF (60 ml), and pyridine (0.12 ml, 1.41 mmol) was added. The reaction mixture Ac 10 Bn S2
was stirred for 15 min at rt and cooled at -78 o C, and a solution of Pb(Ac) 4 (708 mg, 1.60 mmol) in Ac (24 ml) was added. and the stirring continued at rt for 30 h. To remove the remaining Pd salts, a solution of NaB 4 (58 mg, 1.52 mmol) in 1 N Na solution (22 ml) was added to the reaction mixture. The mixture was stirred for 15 min and filtered. The filtrate was diluted with C 2 Cl 2, which was washed with saturated aqueous NaC 3 solution, dried over Na 2 S 4, filtered, and evaporated in vacuo to give a white solid. The solid was purified by silica gel flash column chromatography (petroleum ether/etac: 6/1 to petroleum ether/c 2 Cl 2 : 1/2) to give 10 (791 mg, 72%) as a white foam: [α] 25 D = 75.4 (c 1.00, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.33 (m, 5), 5.30 (s-like, 1), 5.07 (AB, 2), 4.16 (AB, 2), 2.91 (dd, J = 3.3, 13.5 z, 1), 2.76 (ddd, J = 3.3, 6.6, 16.2 z, 1), 2.50 (m, 1), 2.17, 2.05, 1.16, 1.11, 0.95, 0.92, 0.89, 0.63 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 177.4, 170.9, 170.6, 169.7, 143.8, 136.4, 128.4, 128.0, 127.9, 122.2, 68.1, 68.0, 66.0, 48.5, 46.8, 46.7, 45.8, 43.9, 41.8, 41.5, 39.2, 37.0, 36.5, 33.9, 33.1, 32.3, 32.0, 30.7, 27.6, 25.7, 25.6, 23.6, 23.5, 23.1, 21.0, 20.3, 20.0, 19.4, 19.3, 16.8, 15.3; RMS (MALDI) m/z calcd for C 41 57 N 6 Na 682.4078 [M+Na] +, found 682.4096. Bn Na 2 C 3,Me,99% Bn Ac N N Ac 10 S3 A solution of 10 (595 mg, 0.90 mmol) and Na 2 C 3 (478 mg, 4.51 mmol) in Me (90 ml) was stirred at rt for 22 h. After removing Me in vacuo, the resulting colorless solid was dissolved in Et 2. The organic layer was washed with 1 N aqueous Cl solution, saturated aqueous NaC 3 solution and brine, dried over Na 2 S 4, filtered, and evaporated in vacuo to give a solid. The solid was purified by silica gel flash column chromatography (petroleum ether/etac: 4/1) to give S3 (512 mg, 99%) as a white foam: [α] 26 D = 25.1 (c 1.20, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.34 (m, 5), 5.29 (s-like, 1), 5.07 (AB, 2), 3.55 (AB, 2), 3.32 (br, 1), 3.11 (ddd, J = 2.4, 4.8, 18.3 z, 1), 2.90 (dd, J = 4.2, 10.8 z, 1), 1.11 (s, 3), 1.02 (s, 6), 0.91, 0.89, 0.64 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 177.4, 166.1, 143.7, 136.3, 128.3, 127.9, 127.8, 122.2, 67.7, S3
65.9, 49.8, 46.9, 46.7, 45.7, 44.6, 41.7, 41.4, 39.2, 37.8, 36.7, 33.8, 33.0, 32.3, 32.2, 30.6, 27.5, 25.8, 23.6, 23.4, 23.0, 18.8, 18.4, 17.3, 16.9, 15.0; RMS (MALDI) m/z calcd for C 37 54 N 4 576.4047 [M+] +, found 576.4059. Bn TiCl 3,N 4 Ac, TF/ 2, 95% Bn N S3 S4 To a solution of S3 (113 mg, 0.20 mmol) in TF/ 2 (7 ml/7 ml) were added N 4 Ac (189 mg, 2.45 mmol) and a buffered solution of TiCl 3 (0.42 ml of aqueous Cl solution containing 15% TiCl 3, 0.49 mmol). The mixture was stirred at rt for 10 h, and was then extracted with Et 2. The extract was washed with saturated aqueous NaC 3 solution and brine, dried over Na 2 S 4, filtered, and evaporated in vacuo to give a solid. The solid was purified by silica gel flash column chromatography (petroleum ether/etac: 4/1) to give S4 (104 mg, 95%) as a white foam: [α] 26 D = 61.8 (c 1.00, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.33 (m, 5), 5.30 (s-like, 1), 5.07 (AB, 2), 3.64 (d, J = 12.0 z, 1), 3.41 (d, J = 11.7 z, 1), 2.91 (dd, J = 3.6, 13.2 z, 1), 2.62 (m, 1), 2.42 (br, 1), 2.26 (m, 1), 1.94 (m, 4), 1.13, 1.11, 1.02, 0.92, 0.90, 0.67 (s, each 3); ESI-MS m/z 561 [M+] +. Anal. Calcd for C 37 52 4 0.5 2 : C, 77.99;, 9.38. Found: C, 78.11;, 9.19. Bn BnC(N)CCl 3,Tf, dioxane, 0 o C,91% Bn S4 11 Bn To the solution of S4 (2.00 g, 3.57 mmol) and BnC(N)CCl 3 (2.00 g, 7.97 mmol) in dioxane (30 ml, dried over 4Å MS) at 0 o C, was added Tf (0.16 ml, 1.80 mmol) dropwise. After stirring for at 0 o C for 1 h, the reaction mixture was quenched by addition of saturated aqueous NaC 3 solution, diluted with brine, and extracted with C 2 Cl 2. The extract was dried over Na 2 S 4, followed by filtration, concentration in vacuo, and S4
purification by silica gel flash column chromatography (petroleum ether/etac: 20/1) to give 11 (2.10 g, 91%) as a colorless oil: [α] 24 D = 74.3 (c 1.05, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.32 (m, 10), 5.33 (s-like, 1), 5.08 (AB, 2), 4.55 (d, J = 12.3 z, 1), 4.37 (d, J = 12.3 z, 1), 3.52 (d, J = 8.7 z, 1), 3.21 (d, J = 8.7 z, 1), 2.92 (dd, J = 4.2, 13.8 z, 1), 2.44 (m, 1), 1.17, 0.95, 0.93 (s, each 3), 0.91 (s, 6), 0.66 (s, 3); 13 C NMR (125 Mz, CDCl 3 ) δ 216.3, 177.3, 143.6, 138.5, 136.4, 128.3, 128.2, 127.9, 127.8, 127.3, 127.2, 122.4, 75.1, 73.0, 65.9, 51.1, 47.1, 46.7, 46.1, 45.8, 41.8, 41.5, 39.2, 37.2, 36.2, 35.5, 33.8, 33.0, 32.3, 31.9, 30.6, 27.6, 25.7, 23.6, 23.4, 23.0, 19.5, 17.8, 16.8, 15.0; RMS (MALDI) m/z calcd for C 44 58 4 Na 673.4227 [M+Na] +, found 673.4238. Bn 11 Bn 1) LDA, TF, -78 o C,TMSCl, 89% 2) mcpba, C 2 Cl 2,-5to-10 o C 3) TBAF, TF, -5 to -10 o C,94% To TF (10 ml) under stirring at -78 o C, were added i Pr 2 N (3.70 ml, 38 mmol) and n BuLi (20 ml, 1.6 M in hexanes). The stirring continued for 30 min, a solution of 11 (2.10 g, 3.2 mmol) in TF (30 ml) was then added dropwise. After another 1 h, TMSCl (8.20 ml, 64 mmol) was added. After stirring at -78 o C for 1.5 h, the reaction mixture was quenched by addition of saturated aqueous NaC 3 solution, diluted with brine, and extracted with C 2 Cl 2. The extract was dried over Na 2 S 4, followed by filtration, concentration in vacuo, and purification by silica gel flash column chromatography (petroleum ether/c 2 Cl 2 : 3.5/1) to give the silyl enol ether M1 (2.02 g, 89%) as a white foam: 1 NMR (300 Mz, CDCl 3 ) δ 7.26 (m, 7), 7.10 (m, 3), 5.52 (s-like, 1), 5.28 (brs, 1), 4.72 (d-like, J = 4.8 z, 1), 4.61 (d, J = 12.6 z, 1), 4.39 (d, J = 13.2 z, 1), 3.29 (d, J = 8.4 z, 1), 3.05 (d, J = 9.0 z, 1), 2.92 (dd, J = 3.0, 14.4 z, 1), 1.13 (s, 2), 0.95 (s, 1), 0.90 (s, 6), 0.85 (s, 3), 0.71 (s, 3), 0.42 (s, 2), 0.35 (s, 1), 0.16 (s, 9), 0.01 (s, 9); 13 C NMR (75 Mz, CDCl 3 ) δ 177.1, 152.4, 143.5, 143.2, 140.1, 140.0, 139.2, 128.1, 128.0, 127.9, 127.4, 127.1, 126.0, 125.9, 125.8, 123.0, 101.6, 73.0, 72.6, 71.0, 70.9, 46.8, 46.0, 45.9, 44.9, 42.3, 41.8, 41.7, 41.6, 39.4, 39.1, 39.0, 35.8, 34.0, 33.1, 32.6, 31.9, 30.7, 29.7, 27.6, 25.7, 23.5, 23.3, 23.2, 19.2, 16.8, 16.4, 15.8, 15.7, Bn 12 Bn S5
0.5, -3.7, -3.8. To a solution of the silyl enol ether M1 (2.40 g, 3.02 mmol) in C 2 Cl 2 (31 ml) under stirring at -7 o C, was added mcpba (1.11 g containing of 70% of mcpba, 4.53 mmol), followed by quenching with 10% aqueous Na 2 S 2 3 solution after 15 min. The resulting mixture was diluted with brine and extracted with C 2 Cl 2. The extract was dried over Na 2 S 4 and followed concentrated in vacuo. The crude product was dissolved in TF (31 ml) at -7 o C, then TBAF (7.60 ml, 1 M) was added. After stirring at -7 o C for 45 min, the reaction mixture was quenched by addition of saturated aqueous NaC 3 solution, and was then diluted with brine, and extracted with C 2 Cl 2. The extract was dried over Na 2 S 4, filtered, and concentrated in vacuo. Purification of the residue by silica gel column chromatography (petroleum ether/c 2 Cl 2 : 10/1 to 8/1) gave 12 (1.85 g, 94%) as a white foam: [α] 25 D = 48.6 (c 1.12, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.32 (m, 10), 5.31 (s, 1), 5.08 (AB, 2), 4.65 (d, J = 12.3 z, 1), 4.46 (br, 1), 4.44 (d, J = 12.0 z, 1), 3.81 (d, J = 9.3 z, 1), 3.59 (d, J = 2.1 z, 1), 3.17 (d, J = 9.0 z, 1), 2.92 (dd, J = 3.9, 13.8 z, 1), 2.37 (dd, J = 6.3, 12.0 z, 1), 1.22, 1.14, 0.95, 0.93, 0.91, 0.65 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 213.9, 177.1, 143.6, 138.3, 136.2, 128.2, 128.0, 127.8, 127.7, 127.3, 127.2, 121.9, 72.8, 71.1, 69.2, 65.7, 51.2, 48.6, 47.5, 46.9, 46.4, 45.5, 41.6, 41.1, 39.1, 36.8, 33.6, 32.9, 32.1, 31.7, 30.5, 29.5, 27.3, 25.6, 23.4, 23.3, 22.8, 18.4, 17.5, 16.9, 16.2; RMS (MALDI) m/z calcd for C 44 58 5 Na 689.4177 [M+Na] +, found 689.4166. Bn 4N Cl in Me, reflux, 87% Bn 12 13 Bn Bn To a solution of 12 (1.85 g, 2.84 mmol) in Me (30 ml), was added Cl (1 ml, 12 M). The mixture was stirred at reflux for 20 min, followed by quenching with saturated aqueous NaC 3 solution. The mixture was diluted with brine and extracted with C 2 Cl 2. The extract was dried over Na 2 S 4, filtered, and concentrated in vacuo to give a residue, which was purified by silica gel column chromatography (petroleum ether/etac: 13/1) to give 13 (1.60 g, 87%) as a white foam: [α] 25 D = 76.3 (c 1.24, S6
CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.32 (m, 10), 5.30 (s, 1), 5.07 (AB, 2), 4.65 (d, J = 11.7 z, 1), 4.46 (m, 2), 3.42 (d, J = 4.2 z, 1), 3.33 (d, J = 9.3 z, 1), 3.26 (d, J = 9.3 z, 1), 2.92 (dd, J = 2.7, 12.9 z, 1), 2.44 (d, J = 12.0 z, 1), 1.19, 0.93, 0.91, 0.84, 0.57, 0.55 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 212.0, 177.3, 143.8, 138.5, 136.3, 128.3, 128.2, 127.9, 127.8, 127.5, 127.4, 121.7, 72.8, 72.3, 65.9, 52.8, 48.7, 47.3, 46.6, 46.1, 45.7, 43.2, 41.7, 41.3, 39.6, 33.7, 33.0, 32.2, 31.8, 30.6, 27.5, 25.7, 23.5, 23.2, 22.9, 18.0, 16.7, 16.4, 13.2; RMS (MALDI) m/z calcd for C 44 58 5 Na 689.4177 [M+Na] +, found 689.4198. Bn Ac 2, DMAP, pyridine, 95% Bn Ac 13 S5 Bn Bn To a solution of 13 (115 mg, 0.18 mmol) in pyridine (2 ml) under stirring at rt, were added DMAP (4 mg, 0.04 mmol) and Ac 2 (33 μl, 0.35 mmol). After stirring for 19 h, the solution was diluted with EtAc and washed with 1 N aqueous Cl solution and brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo to give a solid, which was purified by silica gel column chromatography (petroleum ether/etac: 12/1) to give S5 (119 mg, 95%) as a white foam: [α] 26 D = 103.4 (c 1.24, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.33 (m, 10), 5.43 (s, 1), 5.30 (s, 1), 5.07 (AB, 2), 5.50 (AB, 2), 3.21 (d, J = 9.9 z, 1), 3.01 (d, J = 9.6 z, 1), 2.92 (dd, J = 4.2, 14.1 z, 1), 2.38 (d, J = 12.0 z, 1), 2.05, 1.19, 0.93, 0.92, 0.87, 0.69, 0.57 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 204.9, 177.1, 169.8, 143.6, 138.0, 136.2, 128.2, 128.1, 127.8, 127.7, 127.6, 127.5, 121.7, 78.6, 72.6, 71.0, 65.7, 53.5, 47.1, 46.7, 46.5, 45.6, 42.5, 41.6, 41.2, 39.5, 33.7, 32.9, 32.1, 31.7, 30.5, 27.4, 25.7, 23.5, 23.2, 22.8, 20.4, 17.9, 16.4, 16.3, 13.9; RMS (MALDI) m/z calcd for C 46 60 6 Na 731.4282 [M+Na] +, found 731.4297. Bn NaB 4,Me/C 2 Cl 2, -10 o C, 95% Bn Ac Ac Bn S5 Bn 14 S7
To a solution of S5 (1.51 g, 2.13 mmol) in C 2 Cl 2 /Me (20 ml/20 ml) under stirring at -10 o C, was added NaB 4 (807 mg, 21.33 mmol). The stirring continued for 30 min, the solution was quenched by addition of saturated aqueous N 4 Cl solution, and then diluted with brine and extracted with C 2 Cl 2. The extract was dried over Na 2 S 4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/etac: 5.2/1) to give 14 (1.44 g, 95%) as a white foam: [α] 24 D = 79.3 (c 1.30, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.33 (m, 10), 5.30 (s-like, 1), 5.10 (d, J = 3.6 z, 1), 5.07 (AB, 2), 4.44 (AB, 2), 4.22 (d, J = 3.6 z, 1), 3.06 (d, J = 9.6 z, 1), 2.91 (br, 1), 2.89 (d, J = 9.6 z, 1), 2.04, 1.25, 1.13, 0.96, 0.92, 0.91, 0.61 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 177.1, 170.0, 143.3, 138.3, 136.0, 128.1, 127.9, 127.7, 127.6, 127.3, 127.1, 122.3, 75.1, 72.5, 72.3, 68.7, 65.6, 47.6, 46.8, 46.4, 45.4, 43.0, 41.5, 41.1, 40.5, 39.0, 36.2, 33.5, 32.9, 32.1, 32.0, 27.2, 25.6, 23.4, 23.2, 22.7, 20.7, 17.2, 16.6, 14.3; RMS (MALDI) m/z calcd for C 46 62 6 Na 733.4439 [M+Na] +, found 733.4465. Bn BnC(N)CCl 3,Tf, dioxane, 0 o C to rt, 100% Bn Bn Ac Ac 14 S6 Bn Bn To a mixture of 14 (142 mg, 0.20 mmol), BnC(N)CCl 3 (150 mg, 0.60 mmol), and 4 Å MS, was added dioxane (2 ml). The mixture was stirred for 1 h at 0 o C, then Tf (6 μl, 0.06mmol) was added dropwise. After stirring for 2 h, the solution was quenched by addition of saturated aqueous NaC 3 solution, and was then diluted with brine and extracted with C 2 Cl 2. The extract was dried over Na 2 S 4, followed by filtration, and concentration in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/etac: 19/1) to give S6 (159 mg, 100%) as a white foam: [α] 26 D = 95.8 (c 1.19, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.26 (m, 15), 5.27 (s, 1), 5.03 (AB, 2), 4.99 (d, J = 3.6 z, 1), 4.53 (d, J = 12.3 z, 1), 4.40, (s, 2), 4.34 (d, J = 11.7 z, 1), 3.97 (d, J = 3.6 z, 1), 3.04 (d, J = 9.3 z, 1), 2.94 (d, J = 9.9 z, 1), 2.87 (dd, J = 3.9, 14.1 z, 1), 2.07 (dd, J = 3.0, 14.4 z, 1), 1.92, 1.18, 1.10, 0.94, 0.89, 0.87, 0.58 (s, each 3); 13 C NMR (125 Mz, CDCl 3 ) δ 177.4, 170.6, 143.7, 139.1, 138.6, S8
136.3, 128.3, 128.2, 128.1, 127.9, 127.8, 127.5, 127.3, 127.1, 126.9, 122.4, 76.4, 74.9, 72.7, 72.4, 71.7, 65.9, 47.8, 47.1, 46.7, 45.7, 41.8, 41.3, 40.9, 40.0, 39.3, 36.7, 33.8, 33.0, 32.3, 32.2, 30.6, 27.4, 25.9, 23.6, 23.5, 23.0, 21.0, 17.5, 16.9, 16.2, 14.3; RMS (MALDI) m/z calcd for C 53 68 6 Na 823.4908 [M+Na] +, found 823.4885. Bn Bn NaMe, Me/C 2 Cl 2, reflux, 93% Bn Bn Ac Bn S6 Bn S7 NaMe (cat.) was added to a solution of S6 (903 mg, 1.13 mmol) in Me/C 2 Cl 2 (10 ml / 10 ml), and was stirred for 49 h at reflux. The mixture was diluted with C 2 Cl 2, washed by 1 N aqueous Cl solution and brine, and dried over Na 2 S 4. Filtration, concentration in vacuo, and purification by silica gel column chromatography (petroleum ether/etac: 13/1) provided S7 (796 mg, 93%) as a white foam: [α] 26 D = 65.3 (c 1.07, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.25 (m, 15), 5.23 (s, 1), 4.99 (AB, 2), 4.68 (d, J = 11.1 z, 1), 4.52 (d, J = 11.7 z, 1), 4.35 (d, J = 12.3 z, 1), 4.22 (d, J = 11.4 z, 1), 4.82 (d, J = 4.2 z, 1), 3.69 (dd, J = 5.1, 10.2 z, 1), 3.34 (d, J = 9.0 z, 1), 3.02 (d, J = 9.6 z, 1), 2.84 (dd, J = 4.2, 12.9 z, 1), 2.60 (d, J = 9.6 z, 1), 2.19 (dd, J = 2.1, 15.0 z, 1), 1.90 (m, 3), 1.11, 1.08, 0.86, 0.84, 0.77, 0.55 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 177.3, 143.7, 138.9, 138.3, 136.3, 128.8, 128.4, 128.3, 128.1, 127.9, 127.8, 127.4, 127.3, 127.2, 127.1, 122.3, 79.2, 73.5, 72.8, 71.6, 71.2, 65.8, 47.8, 46.8, 46.6, 45.7, 41.9, 41.8, 41.3, 39.3, 39.0, 36.5, 33.8, 33.0, 32.3, 32.2, 30.6, 29.6, 27.4, 25.8, 23.6, 23.5, 22.9, 17.5, 16.8, 16.0, 13.6; RMS (MALDI) m/z calcd for C 51 66 5 Na 781.4803 [M+Na] +, found 781.4820. Bn Bn LiI, collidine, reflux, 98% Bn S7 2 Bn Bn LiI (2.24 g, 16.56 mmol) was added to a solution of S7 (1.26 g, 1.66 mmol) in collidine (17 ml). The mixture was stirred for 11 h at reflux, and was then diluted with S9
C 2 Cl 2, washed by 1 N aqueous Cl solution and brine, and dried over Na 2 S 4. Filtration, concentration in vacuo, and purification by silica gel column chromatography (petroleum ether/etac: 6/1) gave 2 (1.09 g, 98%) as a white foam: [α] 25 D = 83.1 (c 1.01, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.28 (m, 10 ), 5.29 (s, 1), 4.73 (d, J = 11.4 z, 1), 4.59 (d, J = 12.3 z, 1), 4.41 (d, J = 12.3 z, 1), 4.28 (d, J = 11.4 z, 1), 3.88 (s, 1), 3.76 (d, J = 3.9 z, 1), 3.38 (d, J = 9.3 z, 1), 3.05 (d, J = 9.0 z, 1), 2.83 (dd, J = 2.4, 12.6 z, 1), 2.25 (d, J = 13.8 z, 1), 1.99 (m, 3), 1.19, 1.14, 0.93, 0.91, 0.76, 0.74 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 184.4, 143.7, 138.9, 138.3, 128.3, 128.1, 127.4, 127.3, 127.2, 122.4, 79.2, 73.5, 72.8, 71.7, 71.3, 47.8, 46.8, 46.4, 45.7, 41.8, 41.6, 40.8, 39.2, 38.9, 36.6, 33.7, 33.0, 32.4, 32.0, 30.6, 27.5, 26.0, 23.5, 23.5, 22.7, 17.4, 17.2, 16.0, 13.5; RMS (MALDI) m/z calcd for C 44 60 5 Na 691.4333 [M+Na] +, found 691.4356. L-Arabinose Bn Bn 7 steps, 46%, ref 1 TMSBr, C 2 Cl 2,rt Bn Ac Bn Ac Ac Br S8 3 TMSBr (0.38 ml, 2.80 mmol) was added to a stirred solution of S8 1 (465 mg, 1.12 mmol) in C 2 Cl 2 (12 ml) at 0 o C. After stirring for 10 h at rt, the solution was evaporated in vacuo to give a light-yellow syrup, which was diluted with EtAc and evaporated (for 3 times to remove the remaining TMSBr). The crude product 3 was used for the next step without further purification. D-Galactose 6 steps, 45% Bn Bn TBDPS PhI(Bz) 2,BF 3 Et 2, Bn TBDPS -45to-25 o C,79% Bn Bz Bz S9 S10 BF 3 Et 2 (0.12 ml, 0.92 mmol) was added to a solution of S9 2 (2.59 g, 4.58 mmol) and PhI(Bz) 2 (2.45 g, 5.49 mmol) in C 2 Cl 2 at -45 o C. After stirring for 30 min, the mixture was warmed up to -25 o C and stirred for 30 min. The solution was cooled to -45 o C and Et 3 N (3.2 ml, 22.77 mmol) was added. The solution was diluted with C 2 Cl 2, washed by brine, and dried over Na 2 S 4. Filtration, concentration in vacuo, and purification by silica gel column chromatography (petroleum ether/etac: 11/1) gave S10 (2.92 g, 79%) as a white foam: [α] 24 D = 111.4 (c 1.28, CCl 3 ); 1 NMR (300 Mz, S10
CDCl 3 ) δ 7.96 (m, 4), 7.44 (m, 26), 5.93 (m, 2), 5.06 (d, J = 11.4 z, 1), 4.65 (m, 3), 4.15 (d, J = 1.8 z, 1), 3.82 (m, 4), 1.07 (s, 9); 13 C NMR (75 Mz, CDCl 3 ) δ 165.2, 165.0, 138.3, 137.5, 135.5, 133.4, 133.1, 133.0, 130.1, 129.8, 129.7, 129.6, 128.7, 128.4, 128.3, 128.2, 128.0, 127.9, 127.8, 127.7, 127.5, 93.2, 79.7, 75.9, 74.8, 72.7, 72.2, 70.9, 61.7, 26.9, 19.2; RMS (MALDI) m/z calcd for C 50 50 8 SiNa 829.3167 [M+Na] +, found 829.3163. Bn Bn TBDPS Bz S10 Bz 1) N 2 4 2,Ac,DMF,rt; 2) CCl 3 CN, DBU, C 2 Cl 2,rt,50% Bn Bn TBDPS Bz N To a solution of S10 (6.42 g, 7.96 mmol) in DMF (75 ml) under stirring at 0 o C, were added N 2 4 2 (2.80 ml, 49.47 mmol) and Ac (2.80 ml, 49.57 mmol). After stirring for 10 h at rt, the solution was diluted with EtAc and washed with water and brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo to give a residue, which was purified by silica gel column chromatography (petroleum ether/etac: 9/1 to 6/1) to give a white foam. The foam was dissolved in C 2 Cl 2 (60 ml), Cl 3 CCN (2.80 ml, 27.74 mmol) and DBU (0.1 ml, 0.56 mmol) were added. After stirring for 2 h at rt, the solution was evaporated in vacuo to give a residue, which was purified by silica gel column chromatography (petroleum ether/etac: 9/1) to give 5 (3.18 g, 50%) as a white foam: [α] 23 D = 68.4 (c 0.96, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 8.39 (s, 1), 7.98 (d, J = 7.8 z, 2), 7.59 (m, 5), 7.30 (m, 18), 6.60 (d, J = 3.6 z, 1), 5.80 (dd, J = 3.6, 11.1 z, 1), 5.04 (d, J = 11.4 z, 1), 4.72 (m, 3), 4.19 (m, 2), 4.07 (t, J = 6.6 z, 1), 3.87 (t, J = 7.2 z, 1), 3.78 (m, 1), 1.05 (s, 9); 13 C NMR (100 Mz, CDCl 3 ) δ 165.5, 160.4, 138.3, 137.8, 135.5, 133.2, 133.1, 129.7, 129.6, 128.4, 128.3, 128.2, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5, 94.5, 76.0, 75.0, 73.9, 73.8, 72.5, 70.2, 62.1, 26.9, 19.2; RMS (MALDI) m/z calcd for C 45 46 N 7 SiCl 3 Na 868.2001 [M+Na] +, found 868.2005. 5 CCl 3 S11
Bz SPh S11 1) i) Bu 2 Sn, toluene, reflux, ii) PMBCl, TBAI, 80 o C; 2)BnBr,Na,TF,0 o Ctort PMB SPh Bn 1) BzCl, Et 3 N, DMAP, C 2 Cl 2, 0 o Ctort; 2) DDQ, C 2 Cl 2 / 2, rt 63% from S11 Bz SPh Bn S12 A mixture of S11 3 (293 mg, 0.81 mmol), Bu 2 Sn (325 mg, 1.30 mmol) in toluene (8 ml) was stirred under reflux, using a Deaan-Stark trap, for 9.5 h. The solution was cooled to ca. 80 o C, and then treated with PMBCl (0.56 ml, 4.14 mmol) and n Bu 4 NI (481 mg, 1.30 mmol). After stirring for 12 h at 80 o C, the mixture was concentrated. The residue was stirred with EtAc (100 ml) at 0 o C for 2 h. The solids were removed by filtration and the filtrate was concentrated. Purification of the residue by silica gel column chromatography (petroleum ether/etac: 4/1) gave a colorless syrup. The syrup was dissolved in TF (10 ml) at 0 o C, followed by addition of Na (82 mg, 60%). After the solution was stirred for 30 min at 0 o C, BnBr (0.24 ml, 2.03 mmol) was added. The stirring continued for 17 h at rt, the solution was then diluted with C 2 Cl 2 and washed with brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo to give a syrup, which was purified by silica gel column chromatography (petroleum ether/etac: 9/2) to give a colorless syrup. The product above was dissolved in C 2 Cl 2 (5 ml) at 0 o C, followed by addition of DMAP (12 mg, 0.10 mmol), Et 3 N (0.41 ml, 2.87 mmol), and BzCl (0.17 ml, 1.43 mmol). After stirring for 9 h at rt, the solution was diluted with C 2 Cl 2 and washed with brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo to give a syrupy, which was purified by silica gel column chromatography (petroleum ether/etac: 19/2) to give a colorless syrup. This syrup was dissolved in C 2 Cl 2 / 2 (6.0 ml/0.36 ml) at rt, and DDQ (358 mg, 1.58 mmol) was added. After stirring for 2 h, the reaction was quenched by addition of saturated aqueous NaC 3 solution. The resulting mixture was diluted with C 2 Cl 2 and washed with brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/etac: 19/2) to give S12 (230 mg, 63%) as a colorless syrupy: [α] 25 D = -105.3 (c 0.78, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 8.08 (d, J = 7.2 z, 2), 7.58 (t, J = 7.2 z, 1), 7.47 (m, 4), 7.31 (m, 8), 5.61 (s, 1), 5.22 (t, J = 9.9 z, 1), 4.78 (d, J = 11.1 z, 1), 4.58 (d, J = 12.0 z, 1), 4.40 (m, S12
1), 4.07 (d, J = 2.4 z, 1), 4.02 (br, 1), 2.50 (d, J = 8.7 z, 1), 1.28 (d, J = 6.6 z, 3); 13 C NMR (75 Mz, CDCl 3 ) δ 166.6, 137.2, 134.1, 133.2, 131.5, 129.8, 129.1, 128.6, 128.4, 128.1, 128.0, 127.5, 85.1, 79.9, 75.6, 72.6, 70.4, 67.5, 17.4; RMS (MALDI) m/z calcd for C 26 26 5 SNa 473.1393 [M+Na] +, found 473.1397. Bz SPh Bn 91% S12 4, TMSTf,4AMS, C 2 Cl 2,-60to-20 o C Bn Bn Bn Bz CA S13 Bn To a mixture of S12 (208 mg, 0.46 mmol), 4 (403 mg, 0.60 mmol), and 4 Å MS, was added dry C 2 Cl 2 (6 ml). The mixture was stirred for 30 min at -60 o C to -20 o C, then TMSTf (0.47 ml, 0.1 M) was added dropwise. After 2.5 h, the reaction was quenched by addition of Et 3 N, and filtered. The filtrate was concentrated in vacuo to give a residue, which was purified by silica gel column chromatography (toluene/c 2 Cl 2 : 1/2) to provide S13 (405 mg, 91%) as a colorless syrup: [α] 24 D = -67.2 (c 0.99, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 8.05 (d, J = 7.2 z, 2), 7.64 (t, J = 7.2 z, 1), 7.54 (t, J = 7.5 z, 2), 7.25 (m, 25), 5.50 (s, 1), 5.49 (t, J = 9.6 z, 1), 4.99 (t, J = 8.7 z, 1), 4.62 (m, 9), 4.31 (m, 1), 4.18 (m, 2), 3.86 (d, J = 14.7 z, 1), 3.75 (d, J = 11.1 z, 1), 3.62 (m, 2), 3.41 (m, 3), 1.22 (d, J = 6.3 z, 3); 13 C NMR (75 Mz, CDCl 3 ) δ 166.0, 165.3, 138.0, 127.9, 137.7, 137.6, 134.1, 133.4, 130.9, 129.5, 129.0, 128.6, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.4, 127.2, 101.1, 86.5, 82.3, 79.2, 77.9, 77.4, 75.3, 75.0, 74.2, 74.0, 73.5, 73.4, 68.7, 67.8, 40.2, 17.2; RMS (MALDI) m/z calcd for C 55 55 11 SClNa 981.3046 [M+Na] +, found 981.3011. SPh Bn Bn Bn Bz CA S13 SPh Bn DABC, Et, 55 o C 86% Bn Bn Bn To a solution of S13 (52 mg, 0.05 mmol) in Et (2.7 ml), was added DABC (93 mg, 0.81 mmol). The solution was stirred at 55 o C for 9 h, and was then diluted with C 2 Cl 2, and washed with 1 N aqueous Cl solution and brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo to give a syrup, which was purified by silica gel column chromatography (petroleum ether/etac: 8/1) to give S14 (41 mg, Bz S14 SPh Bn S13
86%) as a colorless syrup: [α] 24 D = -69.4 (c 1.22, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 8.06 (d, J = 7.2 z, 2), 7.60 (t, J = 7.2 z, 1), 7.47 (t, J = 7.5 z, 2), 7.32 (m, 23), 7.17 (m, 2), 5.50 (t, J = 7.5 z, 1), 5.47 (s, 1), 4.83 (t, J = 10.5 z, 3), 4.71 (d, J = 11.7 z, 1), 4.65 (d, J = 11.1 z, 1), 4.53 (s, 2), 4.51 (d, J = 8.4 z, 1), 4.42 (m, 1), 4.32 (d, J = 7.8 z, 1), 4.25 (d, J = 1.5 z, 1), 4.15 (dd, J = 3.6, 9.9 z, 1), 3.73 (d, J = 7.5 z, 1), 3.62 (dd, J = 4.2, 11.1 z, 1), 3.46 (m, 4), 1.28 (d, J = 6.6 z, 3); 13 C NMR (75 Mz, CDCl 3 ) δ 166.3, 138.6, 138.1, 134.1, 133.1, 130.9, 129.6, 128.9, 128.4, 128.2, 127.8, 127.6, 127.4, 127.2, 104.3, 86.3, 83.7, 79.4, 78.6, 77.1, 75.0, 74.9, 74.8, 74.7, 73.8, 73.4, 73.3, 69.2, 67.7, 17.4; RMS (MALDI) m/z calcd for C 55 53 10 S 905.3354 [M+] +, found 905.3349. Bn Bn Bn Bz SPh SPh (1) BnBr, Na, TF, 0 o Ctort; (2)PMBCl,Na,TBAI,DMF,rt PMB Bn Bn 78% Bn Bn Bn S14 Bn 6 Compound S14 (30 mg, 0.03 mmol) was dissolved in TF (2 ml) at 0 o C, followed by addition of Na (3 mg, 60%). After stirring at 0 o C for 30 min, BnBr (0.01 ml, 0.07 mmol) was added. After stirred for 24 h at rt, the mixture was diluted with C 2 Cl 2 and washed with brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/etac: 7/1) to give a colorless syrup (23 mg). The syrup was dissolved in DMF (2 ml) at 0 o C, followed by addition of Na (2 mg, 60%). After stirring for 30 min at 0 o C, PMBCl (8 μl, 0.05 mmol) and Bu 4 NI (19 mg, 0.05 mmol) were added. After stirring for 7 h at rt, the solution was diluted with C 2 Cl 2 and washed with brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/etac: 15/1) to give 6 (26 mg, 78%) as a colorless syrup: [α] 27 D = -36.9 (c 1.22, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.41 (d, J = 7.5 z, 2), 7.30 (m, 30), 6.79 (d, J = 8.4 z, 2), 5.45 (s, 1), 5.08 (d, J = 11.4 z, 1), 4.98 (d, J = 11.1 z, 1), 4.80 (m, 7), 4.59 (m, 3), 4.38 (d, J = 9.9 z, 1), 4.17 (m, 3), 3.78 (s, 3), 3.69 (m, 5), 3.47 (m, 2), 1.33 (d, J = 6.0 z, 1); 13 C NMR (75 Mz, CDCl 3 ) δ 158.9, 138.3, 138.2, 138.1, 138.0, 137.9, 135.3, 134.5, 130.8, S14
130.1, 129.4, 128.7, 128.2, 128.1, 128.0, 127.8, 127.6, 127.5, 127.4, 127.3, 127.2, 126.8, 113.5, 103.4, 86.1, 84.4, 82.4, 80.7, 80.3, 77.8, 75.4, 74.8, 74.7, 74.3, 73.3, 72.9, 69.1, 68.6, 54.9, 17.6; RMS (ESI) m/z calcd for C 61 64 10 SNa 1011.4112 [M+Na] +, found 1011.4118. BnBr,Na,DMF,rt,80% Bn S15 S16 Compound S15 4 (230 mg, 1.82 mmol) was dissolved in DMF (2 ml) at 0 o C, followed by addition of Na (365 mg, 60%). After the solution was stirred for 30 min at 0 o C, BnBr (1.08 ml, 9.10 mmol) was added. After stirring for 3 h at rt, the solution was diluted with C 2 Cl 2 and washed with brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo to give an oil, which was purified by silica gel column chromatography (petroleum ether/etac: 50/1) to give a colorless oil S16 (315 mg, 80%). 1 NMR (300 Mz, CDCl 3 ) δ 7.36-7.22 (m, 5), 5.97-5.83 (m, 2), 5.12-5.06 (m, 4), 4.47 (s, 2), 2.39-2.34 (m, 4), 1.22 (s, 3); 13 C NMR (75 Mz, CDCl 3 ) δ 139.5, 134.3, 128.2, 127.3, 127.1, 117.5, 76.6, 63.4, 42.7, 23.1. S16 Bn 1) i) 3,Me,-78 o C, ii) 2 2 (30%), C 3 C, reflux 2) Ac 2, rt; 3) PMB, Py, 30% (three steps) C Bn CPMB Diene S16 (200 mg, 0.93 mmol) was dissolved in Me (5 ml) and cooled to -78 o C. zone was passed through the solution until a permanent blue color persisted. The solution was then allowed to warm up to room temperature and the solvent was removed under reduced pressure to yield a colorless oil. This oil was dissolved in acetic acid/hydrogen peroxide (30%) (14 ml, v/v 3:4) and heated under reflux for 6 h. Removal of the solvent under reduced pressure gave an oil. Acetic anhydride (5 ml) was added to the oil and the mixture was stirred at rt for 24 h. The solvent was removed under reduced pressure. This crude product was dissolved in pyridine (3 ml), and PMB (200 mg, 1.45 mmol) was added. The mixture was stirred at rt for 24 h. Evaporation of the solvent in vacuo and purification of the residue by silica gel column chromatography (C 2 Cl 2 /Me: 20/1) gave a colorless oil 7 (104 mg, 30% for three steps). 1 NMR 7 S15
(300 Mz, CDCl 3 ) δ 7.33-7.24 (m, 7), 6.85 (d, J = 11.7 z, 2), 5.07 (s, 2), 4.56-4.50 (AB, 2), 3.80 (s, 3), 2.97-2.74 (m, 4), 1.52 (s, 3). Bn Bn Bn + Bn Ac Br 2 3 TBAB, K 2 C 3, EtAc/ 2, 50 o C 80% Bn Bn 15 Bn Bn Ac To a solution of the bromide 3 and triterpene 2 (150 mg, 0.22 mmol) in EtAc/ 2 (4 ml/4 ml), were added K 2 C 3 (93 mg, 0.67 mmol) and Bu 4 NBr (146 mg, 0.45 mmol). The mixture was stirred at 40 o C for 12 h, and was then diluted with EtAc, and washed with 1 N aqueous Cl solution and brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo to give a yellow solid, which was purified by silica gel column chromatography (toluene/etac: 45/1) to give 15 (184 mg, 80% based on 2) as a white foam: [α] 27 D = 38.1 (c 1.11, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.32 (m, 20), 5.64 (d, J = 4.5 z, 1), 5.33 (brs, 1), 5.26 (t, J = 4.8 z, 1), 4.74 (d, J = 11.4 z, 1), 4.66 (s, 2), 4.59 (m, 3), 4.42 (d, J = 12.3 z, 1), 4.29 (d, J = 11.4 z, 1), 4.10 (dd, J = 6.6, 12.0 z, 1), 3.89 (br, 1), 3.72 (m, 3), 3.52 (dd, J = 3.0, 11.7 z, 1), 3.42 (d, J = 9.3 z, 1), 3.10 (d, J = 8.7 z, 1), 2.87 (d, J = 10.5 z, 1), 2.67 (br, 1), 2.27 (d, J = 14.1 z, 1), 2.03, 1.20, 1.14, 0.89, 0.88, 0.85, 0.76 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 175.8, 169.2, 143.3, 138.9, 138.3, 137.8, 137.7, 128.3, 128.1, 127.7, 127.6, 127.4, 127.3, 127.2, 122.5, 91.1, 79.2, 74.9, 73.5, 72.7, 71.8, 71.6, 71.3, 71.2, 69.0, 61.3, 47.8, 46.8, 46.7, 45.6, 41.9, 41.8, 41.0, 39.2, 39.0, 36.5, 33.7, 33.0, 32.4, 31.9, 30.5, 27.6, 25.6, 23.5, 23.4, 22.5, 20.9, 17.5, 16.9, 16.0, 13.6; RMS (ESI) m/z calcd for C 65 82 10 Na 1045.5800 [M+Na] +, found 1045.5828. S16
in dry C 2 Cl 2 (10 ml) at -40 o C to -20 o C, 40 min later, TMSTf (0.49 ml, 0.1 M) was added dropwise. After stirring for 2 h, the reaction was quenched by addition of Et 3 N. The mixture was filtered. The filtrate was concentrated in vacuo and purified by silica gel column chromatography (toluene/etac: 60/1) to give 16 (1.43 g, 96%) as a white foam: [α] 22 D = 23.1 (c 0.99, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.31 (m, 35), 5.62 (d, J = 4.5 z, 1), 5.32 (brs, 1), 5.26 (t, J = 5.4 z, 1), 5.05 (t, J = 8.1 z, 1), 4.70 (m, 14 ), 4.34 (d, J = 7.8 z, 1), 4.09 (m, 2), 3.68 (m, 9), 3.51 (dd, J = 2.4, 11.4 z, 1), 3.41 (m, 1), 3.14 (d, J = 9.3 z, 1), 3.01 (d, J = 9.0 z, 1), 2.86 (d, J = 10.8 z, 1), 2.03, 1.21, 1.11, 0.89, 0.87, 0.84, 0.74 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 175.8, 169.2, 165.5, 143.2, 140.1, 138.5, 138.1, 138.0, 137.8, 137.7, 128.4, 128.3, 128.2, 127.9, 127.8, 127.7, 127.6, 127.4, 127.3, 127.1, 126.6, 122.7, 101.9, 91.2, 82.6, 81.7, 79.5, 78.1, 75.3, 75.1, 74.9, 74.6, 73.2, 73.1, 72.8, 71.8, 71.3, 71.2, 69.0, 68.7, 61.4, 47.9, 47.4, 46.7, 45.6, 42.2, 42.0, 41.7, 40.9, 40.5, 39.2, 36.5, 33.6, 33.0, 32.5, 31.9, 30.5, 27.6, 25.7, 23.4, 22.5, 20.8, 17.4, 16.9, 16.2, 13.6; RMS (ESI) m/z calcd for C 94 112 16 Cl 1531.7633 [M+] +, found 1531.7828. Bn DABC, Et, 50 o C, 100% Bn Bn Bn Bn CA Bn 16 Bn Bn Ac Bn Bn Bn Bn Bn Bn 17 Ac To a solution of 16 (135 mg, 0.09 mmol) in Et (4.4 ml), was added DABC (148 mg, 1.32 mmol). The solution was stirred at 50 o C for 32 h, then evaporated in vacuo to give a residue, which was purified by silica gel column chromatography (toluene/etac: 25/1) to give 17 (128 mg, 100%) as a white foam: [α] 22 D = 26.6 (c 0.98, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.30 (m, 35), 5.63 (d, J = 4.2 z, 1), 5.33 (brs, 1), 5.26 (t, J = 5.4 z, 1), 5.00 (d, J = 11.4 z, 1), 4.85 (m, 2), 5.54 (m, 11), 4.29 (d, J = 6.6 z, 1), 4.10 (m, 2), 3.66 (m, 9), 3.41 (m, 2), 3.15 (d, J = 9.3 z, 1), 2.86 (d, J = 9.9 z, 1), 2.71 (m, 1), 2.04 (s, 3), 1.25, 1.12, 0.98, 0.89, 0.88, 0.75 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 175.8, 169.2, 143.2, 139.6, 138.7, 138.4, 138.1, 138.0, 137.7, 137.6, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.5, 127.4, S17
CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.30 (m, 35), 5.63 (d, J = 4.2 z, 1), 5.33 (brs, 1), 5.26 (t, J = 5.4 z, 1), 5.00 (d, J = 11.4 z, 1), 4.85 (m, 2), 5.54 (m, 11), 4.29 (d, J = 6.6 z, 1), 4.10 (m, 2), 3.66 (m, 9), 3.41 (m, 2), 3.15 (d, J = 9.3 z, 1), 2.86 (d, J = 9.9 z, 1), 2.71 (m, 1), 2.04 (s, 3), 1.25, 1.12, 0.98, 0.89, 0.88, 0.75 (s, each 3); 13 C NMR (75 Mz, CDCl 3 ) δ 175.8, 169.2, 143.2, 139.6, 138.7, 138.4, 138.1, 138.0, 137.7, 137.6, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.5, 127.4, 127.3, 127.1, 126.8, 122.6, 104.4, 91.1, 84.5, 81.9, 79.1, 75.4, 75.0, 74.9, 74.8, 73.2, 72.6, 72.5, 71.7, 71.3, 71.1, 69.0, 61.4, 47.8, 47.6, 46.7, 45.6, 42.0, 41.7, 40.9, 39.2, 36.5, 33.6, 32.9, 32.4, 31.8, 30.5, 27.5, 25.6, 23.4, 22.5, 20.8, 17.4, 17.0, 16.2, 13.9; RMS (MALDI) m/z calcd for C 92 110 15 Na 1477.7737 [M+Na] +, found 1477.7726. Bn Bn Bn Bn Bn 17 Bn Bn Ac TMSTf, C 2 Cl 2, -40to-20 o C, 65% TBDPS Bn Bn N CCl 3 Bn Bn Bn TBDPS Bn To a mixture of 17 (316 mg, 0.22 mmol), 5 (368 mg, 0.43 mmol), and 4 Å MS, was added dry C 2 Cl 2 (6 ml). The mixture was stirred for 30 min at -40 o C to -20 o C, then TMSTf (0.22 ml, 0.1 M) was added dropwise, followed by addition of 5 (368 mg, 0.43 mmol) in C 2 Cl 2 (2 ml) 30 min later, and another potion of 5 (184 mg, 0.22 mmol) in C 2 Cl 2 (1 ml) after 1 h. The stirring continued for 2.5 h, the reaction was then quenched by addition of Et 3 N. The mixture was filtrated. The filtrate was concentrated in vacuo and purified by silica gel column chromatography (petroleum ether/etac: 9/1) to give 18 (300 mg, 65%) as a white foam: [α] 23 D = 24.1 (c 1.04, CCl 3 ); 1 NMR (500 Mz, CDCl 3 ) δ 7.88 (d, J = 7.4 z, 2), 7.32 (m, 53), 7.05 (m, 2), 6.94 (m, 3), 5.79 (t, J = 9.0 z, 1), 5.67 (d, J = 4.4 z, 1), 5.31 (brs, 1), 5.27 (t, J = 5.2 z, 1), 5.04 (m, 2), 4.60 (m, 13), 4.39 (m, 5), 4.22 (d, J = 7.6 z, 1), 4.18 (d, J = 2.0 z, 1), 4.12 (m, 1), 4.02 (d, J = 4.2 z, 1), 3.93 (t, J = 9.0 z, 1), 3.74 (m, 4), 3.64 (m, 2), 3.59 (d, J = 3.5 z, 1), 3.54 (m, 3), 3.49 (m, 1), 3.41 (m, 2), 3.21 (m, 1), 2.86 (dd, J = 3.6, 13.4 z, 1), 2.76 (d, J = 9.5 z, 1), 2.08, 1.15, 1.12 (s, each 3), 1.05 (s, 5 Bz Bn Bn Bz Bn 18 Bn Bn Ac S18
9), 0.88, 0.87, 0.77, 0.60 (s, each 3); 13 C NMR (125 Mz, CDCl 3 ) δ 175.9, 169.2, 164.9, 143.3, 140.7, 140.4, 138.8, 138.7, 138.3, 138.0, 137.9, 137.8, 135.5, 135.4, 133.3, 132.8, 132.7, 130.1, 129.7, 128.3, 128.2, 128.1, 129.9, 127.8, 127.7, 127.6, 127.5, 127.4, 127.3, 127.2, 127.1, 127.0, 126.7, 126.3, 122.9, 103.8, 100.6, 91.2, 85.6, 83.5, 80.0, 79.9, 78.4, 77.7, 75.0, 74.5, 74.1, 74.0, 73.2, 73.0, 72.7, 72.5, 72.0, 71.7, 71.6, 71.5, 71.3, 69.2, 69.1, 61.2, 61.1, 48.0, 47.6, 46.9, 45.7, 42.5, 42.2, 41.8, 41.1, 39.4, 36.5, 33.8, 33.0, 32.6, 32.0, 30.6, 29.6, 27.7, 26.9, 25.7, 23.6, 23.5, 22.6, 20.9, 19.1, 17.4, 17.1, 16.2, 13.0; RMS (MALDI) m/z calcd for C 135 154 21 SiNa 2162.0644 [M+Na] +, found 2162.0661. Bn Bn Bn TBDPS Bn Bn Bn Bz 18 Bn Bn Ac DBU, Me, C 2 Cl 2,97% Bn Bn Bn TBDPS Bn Bn Bn Bz 19 Bn Bn Bn Bn DBU (0.08 ml, 0.50 mmol) was added to a solution of 18 (154 mg, 0.07 mmol) in Me/C 2 Cl 2 (0.5 ml/1.5 ml) at rt. After stirring for 1 h, the solution was diluted with C 2 Cl 2 and washed with 1 N aqueous Cl solution and brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/etac: 5/1 to 4/1) to give 19 (147 mg, 97%) as a white foam: [α] 23 D = 44.0 (c 1.05, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.88 (d, J = 7.2 z, 2), 7.33 (m, 55), 6.91 (m, 3), 5.80 (dd, J = 7.8, 9.9 z, 1), 5.51 (d, J = 6.9 z, 1), 5.32 (brs, 1), 5.05 (m, 2), 4.56 (m, 18), 4.25 (d, J = 8.1 z, 1), 4.19 (s, 1), 4.06 (m, 1), 4.01 (d, J = 2.7 z, 1), 3.92 (t, J = 9.6 z, 1), 3.62 (m, 14), 3.20 (m, 1), 2.88 (d, J = 9.0 z, 1), 2.75 (d, J = 9.0 z, 1), 2.50 (brs, 1), 1.14 (s, 6), 1.05 (s, 9), 0.90 (s, 6), 0.78, 0.57 (s, each 3); 13 C NMR (100 Mz, CDCl 3 ) δ 176.3, 164.9, 143.4, 140.7, 140.4, 138.8, 138.7, 138.3, 138.1, 138.0, 137.9, 137.8, 135.5, 135.4, 133.3, 132.8, 132.7, 130.2, 129.7, 129.6, 128.4, 128.3, 128.2, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4, 127.2, 127.1, 126.7, 126.3, 122.9, 103.8, 100.6, 94.2, 85.6, 83.5, 80.1, 79.9, 79.8, 78.4, 77.8, 75.0, 74.6, 74.1, 74.0, 73.3, 73.0, 72.9, 72.7, 72.5, 72.0, S19
71.7, 71.6, 71.4, 69.6, 69.1, 63.3, 61.2, 48.0, 47.6, 46.9, 45.8, 42.6, 42.3, 41.9, 41.2, 39.4, 36.5, 33.9, 33.0, 32.5, 32.1, 30.6, 29.6, 27.6, 27.0, 25.7, 23.7, 23.5, 22.8, 19.1, 17.4, 17.2, 16.2, 13.0; RMS (MALDI) m/z calcd for C 133 152 Si 20 Na 2120.0539 [M+Na] +, found 2120.0515. Bn Bn Bn TBDPS Bn Bn Bn Bz Bn 19 Bn Bn 6, NIS, TMSTf,C 2 Cl 2, -40 to -20 o C, 81% Bn Bn Bn TBDPS Bn Bn Bn Bz Bn 20 PMB Bn Bn Bn Bn To a mixture of 19 (90 mg, 0.04 mmol), 6 (127 mg, 0.13 mmol), and 4 Å MS in dry C 2 Cl 2 (2 ml) at -40 o C to -20 o C, was added NIS (29 mg, 0.13 mmol). After stirring for 30 min, TMSTf (0.04 ml, 0.05 M) was added, and the stirring continued at this temperature for 6.5 h. The reaction was quenched by addition of Et 3 N. The mixture was filtered. The filtrate was diluted with C 2 Cl 2 and washed with 10% aqueous Na 2 S 2 3 solution and brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/etac: 6.5/1) to give 20 (103 mg, 81%) as a white foam: [α] 23 D = 8.3 (c 1.10, CCl 3 ); 1 NMR (500 Mz, CDCl 3 ) δ 7.88 (d, J = 4.2 z, 2), 7.55 (d, J = 6.7 z, 2), 7.46 (m, 5), 7.24 (m, 73), 7.05 (m, 2), 6.94 (m, 3), 6.76 (d, J = 8.6 z, 2), 5.91 (s, 1), 5.79 (dd, J = 7.9, 10.0 z, 1), 5.28 (s, 1), 5.05 (m, 3), 4.96 (d, J = 11.0 z, 1), 4.84 (m, 5), 4.62 (m, 15), 4.39 (m, 9), 4.22 (d, J = 7.6 z, 1), 4.18 (m, 2), 4.03 (m, 2), 3.93 (t, J = 9.0 z, 1), 3.82 (dd, J = 1.8, 14.4 z, 2), 3.75 (t, J = 8.6 z, 2), 3.68 (s, 3), 3.67 (m, 12), 3.44 (m, 8), 3.21 (m, 1), 2.86 (dd, J = 3.3, 13.8 z, 1), 2.75 (d, J = 9.5 z, 1), 1.36 (d, J = 6.3 z, 3), 1.16, 1.10 (s, each 3), 1.05 (s, 9), 0.86, 0.84, 0.77, 0.60 (s, each 3); 13 C NMR (100 Mz, CDCl 3 ) δ 175.7, 164.9, 159.1, 143.5, 140.7, 140.5, 138.7, 138.6, 138.5, 138.4, 138.3, 138.2, 138.1, 138.0, 137.8, 135.5, 135.4, 133.3, 132.8, 132.7, 130.4, 130.2, 129.7, 129.5, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4, 127.2, 127.1, 126.8, 126.3, 122.8, 113.7, 103.9, 103.3, Bn Bn Bn S20
100.6, 98.5, 91.3, 85.7, 84.7, 83.6, 82.9, 80.9, 80.1, 80.0, 78.5, 78.1, 77.9, 77.8, 76.8, 75.6, 75.0, 74.9, 74.8, 74.6, 74.3, 74.1, 74.0, 73.7, 73.3, 73.2, 73.1, 72.7, 72.6, 72.5, 71.7, 71.6, 71.4, 69.2, 68.8, 61.2, 58.7, 55.1, 48.0, 47.6, 46.9, 45.7, 42.6, 42.3, 41.8, 41.2, 39.5, 36.5, 33.8, 33.1, 32.6, 32.2, 31.9, 31.4, 30.6, 30.2, 29.7, 29.3, 29.1, 27.7, 27.0, 25.9, 23.6, 23.5, 22.7, 22.6, 19.1, 17.9, 17.5, 17.3, 16.3, 14.1, 13.1; RMS (MALDI) m/z calcd for C 188 210 Si 30 Na 2998.4569 [M+Na] +, found 2998.4545. Bn Bn Bn TBDPS Bn Bn Bn Bn Bn Bn Bz PMB Bn 20 Bn Bn Bn Bn 1) NaMe, Me/C 2 Cl 2,reflux 2)BnBr,Na,TF,0 o Ctort,51% Bn Bn Bn TBDPS Bn Bn Bn Bn 21 Bn PMB Bn Bn Bn Bn To a solution of 20 (80 mg, 0.03 mmol) in C 2 Cl 2 /Me (2 ml/2 ml) was added a solution of NaMe in Me (0.2 M, 0.54 ml). The mixture was stirred for 3 d at reflux. After cooling to rt, the mixture was neutralized with Dowex-50 ( + ). Filtration, concentration in vacuo, and purification by silica gel column chromatography (toluene/etac: 40/1 to 30/1) provided a white foam (47 mg, 61%) and 20 (15 mg, 19%). The white foam was dissolved in TF (1.5 ml) at 0 o C, followed by addition of Na (8 mg, 60%) and BnBr (0.05 ml, 0.42 mmol). After stirring for 24 h at rt, the solution was diluted with C 2 Cl 2 and washed with brine. The organic layer was dried over Na 2 S 4, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (toluene/etac: 40/1) to give 21 (39 mg, 51% based on 20) as a white foam: [α] 25 D = 6.9 (c 0.94 CCl 3 ); 1 NMR (300 Mz, CDCl 3 ) δ 7.25 (m, 84), 6.95 (m, 3), 6.76 (d, J = 11.7 z, 2), 5.91 (s, 1), 5.29 (brs, 1), 4.65 (m, 35), 4.17 (m, 2), 4.04 (m, 3), 3.66 (s, 3), 3.62 (m, 26), 2.84 (d, J = 13.5 z, 1), 2.73 (d, J = 8.4 z, 1), 1.37 (d, J = 5.7 z, 3), 1.17, 1.07 (s, each 3), 1.01 (s, 9), 0.86, 0.84, 0.77, 0.64 (s, each 3); 13 C NMR (100 Mz, CDCl 3 ) δ 175.8, 159.2, 143.6, 140.7, 139.7, 139.3, 139.1, 138.8, 138.7, 138.5, 138.4, 138.3, 138.2, 138.1, 135.6, 135.5, 133.3, 132.9, 130.5, 129.8, 129.6, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, Bn Bn Bn S21
127.5, 127.4, 127.3, 127.2, 127.0, 126.5, 123.0, 113.8, 104.3, 103.5, 102.6, 98.6, 91.4, 86.3, 84.8, 83.5, 83.0, 82.6, 81.1, 81.0, 79.9, 78.6, 78.5, 78.1, 75.8, 75.6, 75.5, 75.1, 74.9, 74.8, 74.4, 74.3, 73.9, 73.8, 73.6, 73.4, 73.1, 72.7, 72.6, 72.3, 71.5, 69.4, 68.9, 68.8, 61.4, 58.9, 55.3, 48.2, 47.7, 47.0, 45.8, 42.5, 41.9, 41.3, 39.6, 36.7, 33.9, 33.2, 32.7, 32.3, 30.8, 29.8, 27.8, 27.1, 26.0, 23.8, 23.7, 22.7, 19.2, 18.0, 17.7, 17.4, 16.4, 13.3; RMS (MALDI) m/z calcd for C 188 212 29 SiNa 2984.4776 [M+Na] +, found 2984.4783. Bn Bn Bn TBDPS Bn Bn Bn Bn Bn Bn Bn Bn Bn TBAF, TF, rt, 98% Bn Bn Bn Bn Bn PMB Bn Bn PMB Bn Bn Bn Bn Bn Bn Bn 21 Bn Bn Bn S17 Bn To a solution of 21 (150 mg, 0.05 mmol) in TF (3 ml) at rt was added Bu 4 NF (1.0 M in TF, 0.3 ml, 0.3 mmol). The solution was stirred at this temperature for 2 h, and was then diluted with C 2 Cl 2, and washed with water. The organic layer was separated and the aqueous layer was extracted with C 2 Cl 2. The combined organic layer was washed with brine, dried over Na 2 S 4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/etac, 3:1) to afford S17 (133 mg, 98%) as a white foam. [α] 27 D = 15.1 (c 1.00, CCl 3 ); 1 NMR (300 Mz, CDCl 3 ): δ 7.36-7.12 (m, 77 ), 6.76 (d, J = 8.7 z, 2 ), 5.88 (br s, 1 ), 5.30 ( br s, 1), 5.10-4.29 (m, 38), 4.19-4.13 (m, 2), 4.03 (t, J = 10.4 z, 1), 3.96-3.30 (m, 34), 2.97-2.84 (m, 2), 1.32 (d, J = 6.6 z, 3), 1.24 (s, 3), 1.09 (s, 3), 0.93 (s, 3), 0.87 (s, 3), 0.85 (s, 3), 0.77 (s, 3); 13 C NMR (75 Mz, CDCl 3 ): δ 175.6, 159.0, 143.4, 139.9, 139.3, 138.7, 138.6, 138.5, 138.3, 138.2, 138.1, 138.0, 137.9, 130.4, 129.3, 128.4, 128.3, 128.2, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.6, 127.5, 127.5, 127.4, 127.3, 127.2, 127.2, 126.8, 122.7, 113.6, 104.1, 103.3, 102.7, 98.4, 91.4, 86.2, 84.6, 83.3, 82.8, 82.2, 80.8, 80.7, 79.6, 78.4, 78.3, 78.0, 75.6, 75.5, 75.1, 75.0, 74.9, 74.8, 74.3, 73.6, 73.3, 73.3, 72.8, 72.5, 72.3, 71.3, 69.3, 68.7, 62.1, 58.8, 55.1, 47.9, 47.5, 46.8, 45.7, 42.4, S22
41.8, 41.1, 39.4, 36.5, 33.7, 33.0, 32.5, 32.1, 30.6, 29.6, 27.6, 25.8, 23.5, 22.5, 17.9, 17.5, 17.2, 16.2, 13.5; RMS (MALDI) calcd for C 172 194 29 Na [M+Na] + : 2746.3609, found 2746.3598. Bn Bn Bn Bn Bn Bn Bn Bn Bn Bn PMB Bn Bn Bn S17 Bn Bn 7, C 6 2 Cl 3 CCl, Et 3 N, toluene, 2 h; then DMAP, 2 h, 96% PMB Bn Bn Bn Bn Bn Bn Bn Bn Bn Bn Bn PMB Bn Bn Bn 22 Bn Bn To a solution of 7 (36 mg, 0.10 mmol) and triethylamine (17 μl, 0.12 mmol) in toluene (0.5 ml) at room temperature was added 2,4,6-trichlorobenzoyl chloride (17 μl, 0.11 mmol). After stirring for 2 h, a solution of S17 (133 mg, 0.050 mmol) and DMAP (17 mg, 0.14 mmol) in toluene (3 ml) was injected to the reaction vessel, and the stirring continued for 1 h. The mixture was concentrated and purified by silica gel column chromatography (petroleum ether/etac, 4:1) to afford 22 (144 mg, 96%) as a white foam. 1 NMR (300 Mz, CDCl 3 ) δ 7.37-7.12 (m, 84), 6.78 (d, J = 7.5 z, 2), 6.76 (d, J = 8.7 z, 2), 5.89 (br s, 1), 5.30-5.29 (m, 1), 5.10-4.12 (m, 50), 4.03 (t, J = 10.4 z, 1), 3.94-3.32 (m, 40), 2.91-2.60 (m, 6), 1.34 (d, J = 5.7 z, 3), 1.22 (s, 3), 1.09 (s, 3), 0.90 (s, 3), 0.86 (s, 3), 0.84 (s, 3), 0.76 (s, 3); RMS (MALDI) calcd for C 193 216 34 Na [M+Na] + : 3100.5039, found 3100.5065. PMB Bn Bn Bn Bn Bn Bn Bn Bn Bn Bn PMB Bn Bn Bn Bn 22 Bn Bn TFA,C 2 Cl 2 /C 6 5 Me, -20 o C, 95% Bn Bn Bn Bn Bn Bn Bn Bn Bn Bn Bn Bn Bn Bn 23 Bn Bn S23
To a solution of 22 (80 mg, 0.026 mmol) in C 2 Cl 2 /C 6 5 Me (2 ml, v/v 1:1) at -20 o C was added trifluoroacetic acid (0.2 ml). The mixture was stirred at this temperature for 3 h, and was then quenched by the addition of NaC 3. The resulting solution was extracted with C 2 Cl 2, and the combined extracts were washed with brine. The organic layer was dried with Na 2 S 4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (C 2 Cl 2 /Me, 20:1) to afford 23 (70 mg, 95%) as a white foam: 1 NMR (300 Mz, CDCl 3 ): δ 7.36-7.13 (m, 80), 5.85 (brs, 1), 5.29 (brs, 1), 5.01-3.39 (m, 68), 2.97-2.83 (m, 2), 2.68-2.39 (m, 3), 1.35 (s, 3), 1.31 (s, 3), 1.23 (s, 3), 1.09 (s, 3), 0.95-0.94 (s, 3), 0.86 (s, 3), 0.87 (s, 3), 0.75 (s, 3). 23 Bn Bn 2,4,6-(C 6 2 Cl 3 )CCl Et Bn Bn 3 N, DMAP. 50% Bn Bn Bn Bn Bn + Bn Bn Bn Bn Bn Bn (S) (R) Bn Bn Bn Bn Bn Bn Bn Bn Bn Bn 24a Bn Bn Bn 24b Bn Bn Bn To a solution of 23 (40 mg, 0.014 mmol) and triethylamine (11 μl, 0.08 mmol) in toluene (1 ml) at room temperature was added 2,4,6-trichlorobenzoyl chloride (11 μl, 0.07 mmol). After stirring for 12 h, the mixture was diluted with toluene (14 ml), and then DMAP (11 mg, 0.09 mmol) was added to the reaction vessel, and the stirring continued for 12 h. The resulting mixture was concentrated and purified by silica gel column chromatography (petroleum ether/etac, 5:1) to afford 24 (20 mg, 50%, 24a:24b = 1 : 1) as a white foam. 24a: 1 NMR (300 Mz, CDCl 3 ): δ 7.40-7.10 (m, 80), 5.73 (brs, 1), 5.48 (t, J = 9.6 z, 1 ), 5.33 (brs, 1), 5.17-5.12 (m, 1 ), 5.02-5.00 (m, 1 ), 4.92-3.35 (m, 68 ), 3.16-3.03 (m, 2 ), 2.87-2.68 (m, 1 ), 2.62-2.43 (m, 1 ), 1.34 (s, 3), 1.23 (s, 3), 1.09 (s, 3), 0.91 (s, 3), 0.90 (s, 3 ), 0.73 (s, 3); RMS (MALDI) calcd for C 177 198 31 Na [M+Na] + : 2842.3791, found 2842.3809. 24b: 1 NMR (300 Mz, CDCl 3 ): δ 7.40-7.10 (m, 80), 5.65 (brs, 1), 5.42-5.30 (m, 3 ), S24
5.13-5.03 (m, 3 ), 4.92-3.35 (m, 70 ), 2.94-2.82 (m, 2 ), 2.57-2.48 (m, 2 ), 2.37-2.32 (m, 1 ), 1.38 (s, 3), 1.23 (s, 3), 1.10 (s, 3), 0.81 (s, 3), 0.73 (s, 3 ); 24a Pd() 2, EA/ethanol, 80% (S) Lobatoside E (1) To a solution of 24a (10 mg, 0.0035 mmol) in EtAc/ethanol (1 ml, v/v 1:1) at room temperature was added Pd() 2 (3 mg). The suspension was stirred under hydrogen pressure for 14 h and then filtered. The filtrate was concentrated, the residue was purified by flash chromatography on DS-silica gel (Me/ 2, 3:1) to afford Lobataside E (1) (4 mg, 80%). Lobataside E (1): [α] 22 D = 6.1 (c 0.20, pyridine) ([α] 22 D = 7.01 (c 0.27, pyridine)) 6 ; 1 NMR (500 Mz, Pyridiene-D 5 / D 2 ): δ 6.09 (s, 1 ), 6.01 (d, J = 6.4 z, 1 ), 6.00 (t, J = 9.7 z, 1 ), 5.48 ( br s, 1 ), 5.17 (br s, 1 ), 5.14 (d, J = 7.4 z, 1 ), 5.09 (d, J = 7.5 z, 1 ), 5.01 (d, J = 7.8 z, 1 ), 4.88 (brs, 1 ), 4.82 (dd, J = 6.8, J = 12.1 z, 1 ), 4.73 (m, 1 ), 4.63-4.60 (m, 2 ), 4.53 (dd, J = 9.8, J = 7.8 z, 1 ), 4.92-4.42 (m, 3 ), 4.36-4.21 (m, 8 ), 4.17-4.00 (m, 6 ), 3.93-3.85 (m, 4 ), 3.75 (m, 1 ), 3.36 (d, J = 15.0 z, 1 ), 3.33 (d, J = 14.7 z, 1 ), 3.23 (d, J = 15.5 z, 1 ), 3.15-3.12 (m, 1 ), 3.04 (d, J = 15.5 z, 1 ), 2.03 (s, 3 ), 1.66 (s, 3 ), 1.54 (s, 3 ), 1.53 (d, J = 6.4 z, 3 ), 1.36 (s, 3 ), 1.24 (s, 3 ), 0.93 (s, 3 ), 0.88 (s, 3 ); 13 C NMR (125 Mz, Pyridiene-D 5 ): δ 176.2, 171.3, 170.8, 144.1, 123.2, 106.1, 105.7, 105.1, 102.0, 94.5, 83.0, 82.2, 79.0, 77.9, 77.6, 77.6, 77.2, 76.7, 75.1, 75.0, 74.9, 73.5, 73.3, 73.1, 72.0, 71.7, 71.5, 70.9, 70.7, 70.3, 68.8, 67.9, 66.7, 66.4, 64.6, 62.6, 62.4, 48.4, 47.6, 47.5, 47.1, 46.9, 46.1, 44.1, 42.7, 42.2, 41.5, 39.9, 36.9, 34.1, 33.3, 33.0, 32.2, 30.7, 28.9, 26.0, 25.5, 23.9, 23.4, 22.8, 18.8, 18.4, 17.7, 17.4, 15.4; RMS (MALDI) calcd for C 65 102 31 Na [M+Na] + : 1404.6276, found 1401.6297. S25
24b Pd() 2, EA/ethanol, 80% (R) 25 To a solution of 24b (10 mg, 0.0035 mmol) in EtAc/ethanol (1 ml, v/v 1:1) at room temperature was added Pd() 2 (3 mg). The suspension was stirred under hydrogen pressure for 14 h and then filtered. The filtrate was concentrated, the residue was purified by flash chromatography on DS-silica gel (Me/ 2, 3:1) to afford 25 (4 mg, 80%). 25: [α] 22 D = 1.3 (c 0.20, pyridine); 1 NMR (500 Mz, pyridiene-d 5 /D 2 ): δ 6.16 (s, 1 ), 6.00 (d, J = 5.5 z, 1 ), 5.97 (t, J = 10.0 z, 1 ), 5.47 ( br s, 1 ), 5.17 (br s, 1 ), 5.13 (d, J = 6.5 z, 1 ), 5.08 (d, J = 7.3 z, 1 ), 5.05 (d, J = 7.8 z, 1 ), 4.88 (brs, 1 ), 4.77 (m, 2 ), 4.63 (m, 2 ), 4.56 (m, 1 ), 4.44-3.89 (m, 20 ), 3.57-3.49 (m, 7 ), 3.40 (d, J = 16.7 z, 1 ), 3.35 (d, J = 14.3 z, 1 ), 3.23 (d, J = 18.0 z, 1 ), 3.19-3.15 (m, 3 ), 1.98 (s, 3 ), 1.68 (s, 3 ), 1.53 (s, 3 ), 1.48 (d, J = 5.2 z, 3 ), 1.28 (s, 3 ), 1.25 (s, 3 ), 0.91 (s, 3 ), 0.87 (s, 3 ); 13 C NMR (125 Mz, pyridine-d 5 ): δ 176.1, 171.2, 170.9, 144.0, 123.1, 106.2, 106.0, 105.0, 101.7, 94.3, 82.8, 81.6, 79.3, 78.0, 77.7, 77.5, 76.9, 76.3, 75.1, 75.0, 74.6, 73.5, 73.3, 73.0, 72.0, 71.4, 70.9, 70.5, 70.4, 69.7, 68.7, 67.7, 66.5, 66.5, 64.2, 62.5, 62.2, 48.4, 47.4, 47.0, 47.0, 46.5, 46.0, 44.1, 42.6, 42.1, 41.1, 39.7, 37.1, 33.9, 33.3, 32.8, 31.9, 30.5, 28.5, 25.9, 25.2, 23.8, 23.3, 22.7, 18.7, 18.3, 17.5, 17.2, 15.2. Table S1. Comparison of the diagnostic 1 NMR signals of the synthetic 1, 25, and the natural Lobatoside E. Position Natural product 6 Synthetic 1 Synthetic 25 28Rha-1 6.09 brs 6.09 brs 6.16 brs 28Ara-1 6.01 d (6) 6.01 d (6.4) 6.00 d (5.5) S26
28Rha-4 6.00 t (10) 6.00 t (9.7) 5.97 t (10) -12 ca. 5.45 5.48 5.47 28Rha-2 5.15 dd (1.5, 3) 5.17 brs 5.17 brs 3Glc-1 5.12 d (8) 5.14 d (7.4) 5.13 d (6.5) 3Gal-1 5.07 d (7.5) 5.09 d (7.5) 5.08 d (7.3) 28Glc-1 5.02 d (8) 5.01 d (7.8) 5.05 d (7.8) -2 4.85 brs 4.88 brs 4.88 brs 3Gla-6 4.73 dd (2, 12) 4.73 m 4.77 m 4.82 dd (7, 12) 4.82 dd (6.8, 12.1) 4.77 m Dicrotalic acid moiety 2 (4 ) 3.01 d (16) 3.04 d (15.5) 3.12 d (17) 3.30 d (16) 3.33 d (14.7) 3.35 d (14.3) 4 (2 ) 3.19 d (17) 3.23 d (15.5) 3.23 d (18) 3.32 d (17) 3.36 d (15) 3.40 d (16.7) 6 2.01 s 2.03 s 1.98 s -24 1.53 s 1.54 s 1.53 s -25 1.65 s 1.66 s 1.68 s -26 1.23 s 1.24 s 1.25 s -27 1.35 s 1.36 s 1.31 s -29 0.92 s 0.93 s 0.91 s -30 0.88 s 0.88 s 0.87 s Table S2. Comparison of the 13 C NMR data of the synthetic 1, 25, and the natural Lobatoside E. Position Natural product 6 Synthetic 1 Synthetic 25 C1 44.2 44.1 44.1 C2 70.7 70.7 70.4 a C3 83.2 83.0 82.8 S27
C4 42.7 42.7 42.6 C5 48.5 48.4 48.4 C6 18.8 18.8 18.7 C7 33.4 33.3 33.3 C8 40.0 39.9 39.7 C9 47.6 47.6 47.4 C10 37.0 36.9 37.1 C11 24.0 23.9 23.8 C12 123.2 123.2 123.2 C13 144.1 144.1 144.0 C14 42.3 42.2 42.1 C15 28.9 28.9 28.5 C16 22.9 22.8 22.7 C17 47.2 47.1 47.0 C18 41.6 41.5 41.1 C19 46.2 46.1 46.0 C20 30.7 30.7 30.5 C21 34.1 34.1 33.9 C22 32.3 32.2 31.9 C23 64.7 64.6 64.2 C24 15.4 15.4 15.2 C25 17.4 17.4 17.2 C26 17.7 17.7 17.5 C27 25.6 25.5 25.2 C28 176.2 176.2 176.1 C29 33.1 33.0 32.8 C30 23.5 23.4 23.3 Dicrotalic acid moiety S28
1 171.3 171.3 171.2 2 47.0 46.9 46.5 3 70.3 70.3 69.7 a 4 47.5 47.5 47.0 5 170.9 170.8 170.9 6 26.1 26.0 25.9 3Glc-1 105.0 105.1 105.0 3Glc-2 82.3 82.2 81.6 3Glc-3 77.2 77.2 76.9 3Glc-4 71.6 71.5 70.9 a 3Glc-5 77.6 77.6 77.5 3Glc-6 62.5 62.4 62.2 3Gal-1 106.1 106.1 106.2 3Gal-2 75.0 75.0 75.0 3Gal-3 73.4 73.3 73.3 3Gal-4 70.9 70.9 70.5 a 3Gal-5 75.1 75.1 75.1 3Gal-6 66.6 66.7 66.5 28Ara-1 94.5 94.5 94.3 28Ara-2 76.6 76.7 76.3 28Ara-3 73.6 73.5 73.5 28Ara-4 68.8 68.8 68.7 28Ara-5 66.5 66.4 66.5 28Rha-1 101.9 102.0 101.7 28Rha-2 72.1 72.2 72.0 28Rha-3 79.1 79.0 79.3 28Rha-4 73.2 73.1 73.0 28Rha-5 67.9 67.9 67.7 S29
28Rha-6 18.4 18.4 18.3 28Glc-1 105.7 105.7 106.0 28Glc-2 74.9 74.9 74.6 28Glc-3 77.9 77.9 78.0 28Glc-4 71.7 71.7 71.4 a 28Glc-5 77.7 77.6 77.5 28Glc-6 62.7 62.6 62.5 a) These values may be interchanged. References (1) Yang, G. B.; Kong, F. Z. Bioorg. Med. Chem. Lett. 2006, 13, 909. (2) Timmers, C. M.; Wigchert, S. C. M.; Leeuwenburgh, M. A.; Van der Marel, G.; Van Boom, J.. Eur.J. rg. Chem. 1998, 58, 91. (3) Yang, Z. Y.; Yu, B. Carbohydr. Res. 2001, 333, 105. (4) Lewer, P.; MacMillan, J. J. Chem. Soc., Perkin Trans. 1 1983, 1417. (5) Nicolaou, K. C.; Koumbis, A. E.; Takayanagi, M.; Natarajan, S.; Jain, N. F.; Bando, T.; ughes, R.; Winssinger, N.; Natarajan, S.; Koumbis, A. E. Chem. Eur. J. 1999, 5, 2648. (6) Fujioka, T.; Iwamoto, M.; Iwase, Y.; achiyama, S.; kabe,.; Yamauchi. T.; Mihashi, K. Chem. Pharm. Bull. 1989, 37, 2355. S30
7.354 7.349 7.341 7.329 7.281 7.260 5.297 5.122 5.082 5.065 5.024 3.113 3.098 3.086 3.061 3.044 3.033 2.935 2.922 2.888 2.875 2.207 2.189 2.165 2.146 2.114 2.095 2.028 2.018 1.983 1.968 1.938 1.922 1.895 1.862 1.851 1.145 1.102 1.048 0.994 0.916 0.892 0.636 9 4.86 1.62 2.02 0.99 1.00 0.98 2.91 6.02 2.852.98 3.02 3.57 2.89 7 6 5 4 3 2 1 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S31
S32
7.344 7.334 7.295 7.261 5.118 5.075 5.302 5.062 5.020 4.203 4.167 4.148 4.112 2.937 2.926 2.892 2.838 2.807 2.797 2.788 2.775 2.753 2.742 2.731 2.719 2.556 2.531 2.521 2.498 2.476 2.465 2.441 2.167 2.047 2.027 2.013 1.980 1.969 1.934 1.925 1.889 1.854 1.160 1.113 0.946 0.916 0.894 0.633 10 9.78 5.08 1.03 2.10 2.05 1.00 1.00 1.01 3.22 3.15 3.17 3.38 2.98 3.08 7 6 5 4 3 2 1 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S33
177.385 170.922 170.556 169.719 143.799 136.400 128.433 128.039 128.016 127.954 122.210 77.488 77.063 76.631 68.104 67.983 65.974 48.491 46.792 46.706 45.826 43.889 41.829 41.525 39.234 37.013 36.468 33.870 33.096 32.328 32.027 30.710 27.557 25.672 23.629 23.463 23.054 20.983 20.247 20.020 19.330 16.786 15.289 10 180 160 140 120 100 80 60 40 20 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S34
7.355 7.341 7.328 7.322 7.300 7.263 5.298 5.293 5.280 5.122 5.080 5.067 5.026 4.135 4.111 3.641 3.629 3.589 3.525 3.488 3.407 3.385 3.361 3.315 3.159 3.150 3.144 3.137 3.098 3.090 3.082 2.935 2.921 2.889 2.877 2.848 2.385 2.107 2.088 2.062 2.047 2.009 1.986 1.970 1.939 1.897 1.871 1.860 1.111 1.027 0.916 0.892 0.640 5.09 1.00 0.96 1.42 2.11 1.01 1.09 1.02 4.40 6.25 3.09 3.03 3.09 3.01 8 7 6 5 4 3 2 1 S35
S36
7.362 7.352 7.311 7.271 5.310 5.307 5.133 5.092 5.080 5.037 3.664 3.626 3.437 3.399 2.951 2.937 2.905 2.892 2.690 2.667 2.647 2.637 2.624 2.613 2.592 2.569 2.300 2.291 2.282 2.253 2.246 2.236 2.049 2.045 1.999 1.985 1.950 1.938 1.915 1.904 1.138 1.114 1.023 0.927 0.903 0.671 29 4.33 1.17 2.05 1.00 1.01 1.00 1.05 1.14 4.18 6.54 3.11 6.10 3.03 7 6 5 4 3 2 1 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S37
7.344 7.331 7.306 7.289 7.264 7.246 5.329 5.128 5.086 5.071 5.029 4.566 4.525 4.393 4.351 3.534 3.505 3.225 3.195 2.957 2.943 2.911 2.896 2.469 2.452 2.440 2.422 1.172 0.953 0.929 0.911 0.655 11 10.28 12.07 1.00 2.03 0.97 0.96 0.97 0.94 0.98 1.91 4.13 2.80 7 6 5 4 3 2 1 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S38
S39
S40
S41
7.344 7.311 7.293 7.258 5.303 5.126 5.084 5.068 5.026 4.660 4.619 4.471 4.446 4.406 3.816 3.785 3.582 3.575 3.183 3.153 2.946 2.934 2.900 2.886 2.393 2.372 2.353 2.330 2.044 2.003 1.958 1.926 1.253 1.209 1.128 0.943 0.923 0.903 0.638 12 9.79 1.06 9.02 4.19 1.00 2.02 3.68 2.18 2.78 0.92 0.94 0.91 0.99 0.93 3.10 7 6 5 4 3 2 1 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S42
S43
7.338 7.290 7.259 5.296 5.119 5.077 5.061 5.020 4.668 4.629 4.470 4.450 4.431 3.430 3.417 3.368 3.352 3.320 3.276 3.245 2.938 2.904 2.894 2.462 2.422 2.105 2.061 2.015 2.003 1.967 1.190 0.925 0.910 0.842 0.572 0.552 13 10.45 1.23 2.31 1.00 2.15 0.99 2.45 1.09 0.94 3.18 4.39 7.05 3.44 6.13 7 6 5 4 3 2 1 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S44
S45
7.351 7.336 7.321 7.305 7.282 7.264 5.421 5.300 5.125 5.083 5.061 5.019 4.548 4.506 4.487 4.445 3.229 3.196 3.016 2.984 2.955 2.941 2.908 2.896 2.400 2.360 2.050 1.628 1.190 0.927 0.915 0.867 0.690 0.573 Bn Ac Bn S5 10.14 1.68 2.13 3.00 2.05 0.97 0.96 0.99 1.00 1.02 3.32 6.07 2.98 2.97 2.98 7 6 5 4 3 2 1 PPM S46
204.880 177.054 169.741 143.555 137.982 136.099 128.167 128.115 127.793 127.708 127.508 127.439 121.606 78.537 77.371 76.944 76.510 72.542 70.907 65.687 53.446 47.026 46.608 46.427 45.533 42.428 41.567 41.108 39.398 33.598 32.881 32.074 31.680 30.471 27.342 25.613 23.411 23.100 22.764 20.343 17.809 16.349 16.251 13.891 32 200 150 100 50 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S47
7.353 7.348 7.338 7.324 7.308 7.290 7.260 5.301 5.123 5.105 5.093 5.081 5.060 5.018 4.491 4.449 4.427 4.386 4.225 4.213 3.079 3.048 2.911 2.879 2.042 1.247 1.130 0.955 0.921 0.904 0.610 14 9.72 8.95 0.99 2.95 3.42 3.68 1.00 3.07 2.70 1.96 1.94 0.95 7 6 5 4 3 2 1 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S48
177.103 170.084 143.336 138.329 136.080 128.109 127.947 127.723 127.629 127.328 127.140 122.322 77.473 77.037 76.616 75.182 72.565 72.366 68.797 65.638 47.644 46.872 46.415 45.498 43.048 41.543 41.118 40.536 39.056 36.212 33.603 32.904 32.133 32.006 30.406 27.216 25.661 23.415 23.237 22.773 20.771 17.285 16.643 14.305 14 180 160 140 120 100 80 60 40 20 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S49
7.340 7.326 7.318 7.297 7.285 7.268 7.259 5.304 5.125 5.084 5.055 5.040 5.027 5.015 4.583 4.543 4.441 4.398 4.358 4.013 4.001 3.093 3.062 2.993 2.960 2.940 2.927 2.894 2.886 2.881 2.139 2.128 2.090 2.079 1.959 1.596 1.221 1.138 0.976 0.924 0.908 0.620 33 15.10 6.21 1.00 3.09 1.99 1.01 1.02 0.98 1.02 1.01 1.01 0.95 2.99 3.27 3.10 3.12 2.91 7 6 5 4 3 2 1 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S50
177.429 170.608 143.755 139.127 138.666 136.359 128.361 128.182 128.130 127.938 127.861 127.566 127.350 127.104 126.957 122.432 77.458 77.032 76.602 76.390 74.935 72.775 72.419 71.739 65.895 47.816 47.081 46.703 45.714 41.843 41.340 40.894 40.063 39.358 36.715 33.809 33.089 32.352 32.248 30.656 27.460 25.916 23.633 23.535 22.988 21.057 17.535 16.965 16.234 14.352 33 180 160 140 120 100 80 60 40 20 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S51
7.281 7.271 7.252 7.242 7.232 7.219 7.207 7.190 5.239 5.055 5.012 5.012 4.989 4.946 4.701 4.663 4.539 4.500 4.367 4.326 4.237 4.199 3.825 3.811 3.711 3.697 3.679 3.663 3.358 3.329 3.045 3.012 2.868 2.854 2.826 2.624 2.591 2.224 2.216 2.174 2.167 1.977 1.948 1.933 1.919 1.888 1.855 1.843 1.106 1.076 0.855 0.837 0.772 0.546 Bn Bn Bn S7 15.10 1.05 2.17 0.93 0.98 1.00 0.97 0.94 0.96 0.93 0.97 0.94 0.89 0.91 3.17 3.17 2.96 3.17 2.98 2.90 2.95 7 6 5 4 3 2 1 PPM S52
177.334 143.739 138.896 138.339 136.298 128.308 128.291 128.109 127.893 127.812 127.387 127.287 127.242 127.176 122.313 77.421 79.228 77.000 76.579 73.540 72.756 71.631 71.229 65.851 47.792 46.789 46.637 45.711 41.862 41.776 41.288 39.255 39.039 36.489 33.772 33.050 32.280 32.174 30.615 29.617 27.423 25.841 23.579 23.478 22.950 17.502 16.829 15.983 13.577 34 180 160 140 120 100 80 60 40 20 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S53
7.373 7.328 7.313 7.289 7.254 7.226 7.226 5.291 4.747 4.708 4.612 4.571 4.431 4.390 4.301 4.262 3.880 3.767 3.753 3.404 3.374 3.075 3.045 2.855 2.845 2.811 2.802 2.279 2.233 2.045 2.022 1.992 1.946 1.191 1.143 0.933 0.912 0.764 0.735 2 10.65 1.06 1.07 1.02 1.01 1.00 0.98 1.02 1.00 0.97 1.12 1.00 3.06 2.95 3.02 6.14 2.87 2.94 7 6 5 4 3 2 1 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S54
184.374 138.876 143.695 138.305 128.417 128.400 128.359 128.324 128.295 128.140 128.101 127.433 127.324 127.294 127.267 127.109 126.869 122.434 79.246 77.421 77.000 76.579 73.458 72.792 71.660 71.351 47.818 46.777 46.444 45.715 41.836 41.585 40.801 39.213 38.925 36.599 33.703 33.028 32.388 31.981 30.599 27.500 25.964 23.534 23.456 22.720 17.441 17.210 15.956 13.448 2 180 160 140 120 100 80 60 40 20 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S55
7.984 7.970 7.960 7.946 7.625 7.614 7.600 7.593 7.556 7.531 7.507 7.482 7.457 7.420 7.394 7.370 7.345 7.318 7.292 7.274 7.253 7.230 5.975 5.947 5.921 5.899 5.077 5.039 4.715 4.690 4.674 4.653 4.633 4.592 4.153 4.147 3.945 3.913 3.885 3.862 3.844 3.828 3.812 3.793 3.757 3.738 3.712 1.065-0.000 Bn Bn TBDPS Bz Bz S10 26.04 9.07 3.97 1.91 1.00 3.14 1.00 4.31 8 7 6 5 4 3 2 1 PPM S56
165.244 164.982 138.345 137.467 135.508 133.437 133.069 133.054 133.023 130.130 129.828 129.780 129.741 129.660 128.736 128.401 128.300 128.271 128.200 128.004 127.890 127.828 127.758 127.740 127.493 93.174 79.684 77.425 77.000 76.566 75.884 74.847 72.676 72.169 70.875 61.712 26.903 19.184 37 160 140 120 100 80 60 40 20 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S57
8.383 7.995 7.968 7.617 7.601 7.595 7.578 7.556 7.531 7.435 7.409 7.396 7.359 7.336 7.313 7.285 7.274 7.263 7.254 6.607 6.595 5.822 5.810 5.785 5.774 5.053 5.015 4.741 4.716 4.676 4.201 4.191 4.175 4.166 4.090 4.068 4.045 3.903 3.869 3.844 3.805 3.786 3.772 3.752 1.044 5 18.84 9.30 5.46 0.88 1.91 0.93 0.95 1.00 2.99 1.98 1.06 1.12 1.16 8 7 6 5 4 3 2 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S58
S59
8.095 8.071 7.609 7.584 7.560 7.484 7.478 7.471 7.459 7.450 7.446 7.435 7.352 7.332 7.307 7.288 7.258 5.614 5.249 5.217 5.184 4.798 4.761 4.596 4.556 4.453 4.433 4.413 4.401 4.381 4.359 4.079 4.076 4.068 4.019 2.522 2.499 1.607 1.290 1.268-0.001 8.01 4.02 3.25 1.96 1.05 1.00 1.00 1.01 1.03 1.02 2.07 0.85 8 7 6 5 4 3 2 1 PPM S60
S61
8 7 6 5 4 3 2 1 8.064 8.040 7.667 7.643 7.619 7.535 7.511 7.485 7.389 7.364 7.329 7.307 7.289 7.254 7.202 7.178 7.154 7.130 5.521 5.501 5.490 5.457 5.292 5.019 4.991 4.961 4.843 4.802 4.781 4.745 4.711 4.671 4.656 4.619 4.564 4.539 4.513 4.493 4.456 4.344 4.323 4.311 4.291 4.219 4.209 4.177 4.169 3.885 3.836 3.769 3.733 3.656 3.640 3.609 3.578 3.494 3.471 3.422 3.414 3.381 3.352 1.601 1.253 1.228 1.208 2.02 2.03 1.03 2.13 26.93 1.09 2.05 1.02 1.06 2.03 3.08 1.00 9.49 3.03 S62
S63
8.075 8.051 8.047 7.627 7.603 7.578 7.499 7.473 7.448 7.383 7.358 7.287 7.275 7.267 7.254 7.185 7.176 7.161 7.155 5.530 5.498 5.470 5.292 4.868 4.830 4.797 4.724 4.685 4.669 4.631 4.530 4.502 4.436 4.416 4.404 4.382 4.337 4.311 4.246 4.241 4.171 4.160 4.139 4.127 4.108 3.758 3.747 3.722 3.648 3.634 3.611 3.598 3.543 3.510 3.486 3.429 3.399 3.371 2.436 2.046 1.645 1.293 1.271 23.92 2.00 1.00 2.03 2.12 1.97 3.01 3.05 2.09 1.03 1.08 1.21 1.00 1.02 1.00 4.38 0.85 3.48 8 7 6 5 4 3 2 S64
S65
7 6 5 4 3 2 PPM 7.421 7.396 7.366 7.339 7.334 7.295 7.287 7.257 7.238 7.216 7.207 7.186 7.152 6.804 6.776 5.454 5.296 5.102 5.064 4.997 4.960 4.869 4.833 4.803 4.785 4.764 4.752 4.723 4.628 4.612 4.588 4.566 4.526 4.396 4.363 4.222 4.180 4.154 4.111 3.777 3.725 3.694 3.655 3.525 3.499 3.469 3.443 2.303 1.592 1.342 1.322 1.254 1.96 0.93 31.57 2.03 0.93 0.96 0.96 2.94 6.92 3.00 2.00 2.99 4.82 3.08 6 S66
S67
7.364 7.335 7.330 7.315 7.289 7.236 7.216 5.967 5.943 5.936 5.918 5.910 5.852 5.828 5.118 5.112 5.081 5.073 5.071 5.066 5.060 4.466 2.391 2.367 2.363 2.348 2.342 1.217 0.000 5.38 4.07 4.10 3.13 2.00 2.04 7 6 5 4 3 2 1 PPM S68
S69
7.327 7.304 7.286 7.263 7.237 6.864 6.835 5.074 4.549 4.535 3.816 3.802 2.918 2.883 2.837 2.783 1.521 1.253 0.000 11.45 3.13 3.38 3.10 1.72 2.00 2.08 8 7 6 5 4 3 2 1 0 PPM S70
7.383 7.339 7.321 7.306 7.280 7.255 5.645 5.630 5.334 5.272 5.255 5.235 5.005 4.764 4.726 4.698 4.660 4.610 4.587 4.570 4.441 4.400 4.309 4.271 4.136 4.114 4.096 4.075 3.885 3.765 3.755 3.743 3.716 3.696 3.686 3.547 3.537 3.508 3.499 3.437 3.407 3.120 3.091 2.883 2.848 2.693 2.668 2.294 2.249 2.033 2.008 1.989 1.943 1.938 1.935 1.900 1.861 1.647 1.198 1.139 0.888 0.877 0.846 0.764 15 20.30 9.05 1.01 0.92 0.97 0.93 2.05 2.96 1.00 0.92 0.99 0.93 2.97 0.98 0.94 0.91 0.92 0.77 0.93 3.00 2.83 3.76 3.27 3.08 7 6 5 4 3 2 1 PPM S71
175.835 169.167 138.886 143.315 138.333 137.757 137.713 128.420 128.297 128.281 128.111 127.702 127.681 127.666 127.389 127.304 127.260 127.182 122.480 91.128 79.211 77.431 77.000 76.579 74.899 73.515 72.754 71.813 71.618 71.319 71.210 71.182 69.025 61.310 47.774 46.784 46.757 45.628 41.870 41.823 40.969 39.259 39.026 36.510 33.669 32.968 32.375 31.883 30.542 27.594 25.663 23.493 23.441 22.534 20.876 17.514 16.924 16.017 13.585 15 180 160 140 120 100 80 60 40 20 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S72
7.399 7.380 7.332 7.308 7.273 7.268 7.253 7.251 7.219 7.190 5.631 5.617 5.321 5.321 5.276 5.255 5.239 5.072 5.045 5.017 4.864 4.824 4.781 4.766 4.725 4.688 4.653 4.616 4.588 4.541 4.529 4.500 4.479 4.462 4.423 4.358 4.330 4.125 4.104 4.087 4.065 4.045 4.045 3.797 3.747 3.735 3.705 3.685 3.672 3.639 3.622 3.608 3.579 3.527 3.496 3.488 3.411 3.402 3.385 3.161 3.131 3.027 2.997 2.874 2.834 2.029 1.206 1.114 0.887 0.874 0.836 0.739 16 36.47 14.45 9.07 8.95 0.96 0.92 0.96 0.98 0.97 1.98 1.05 0.97 0.930.910.95 3.03 3.23 3.00 2.82 8 7 6 5 4 3 2 1 PPM S73
S74
7 6 5 4 3 2 1 PPM 7.413 7.390 7.343 7.312 7.289 7.255 5.637 5.623 5.322 5.278 5.260 5.241 5.007 4.970 4.865 4.836 4.701 4.659 4.592 4.574 4.550 4.534 4.495 4.457 4.419 4.380 4.300 4.278 4.134 4.110 4.093 4.075 3.795 3.764 3.742 3.710 3.666 3.647 3.613 3.589 3.575 3.560 3.534 3.501 3.426 3.397 3.168 3.137 2.876 2.843 2.723 2.696 2.032 1.241 1.119 0.975 0.890 0.877 0.748 1.00 37.41 1.00 0.97 0.99 2.07 11.76 0.98 2.07 9.58 2.03 0.94 0.97 0.90 2.99 2.93 6.14 3.03 3.15 3.13 17 Bn Bn Bn Bn Bn Ac Bn Bn S75
S76
S77
S78
7.893 7.869 7.561 7.539 6.929 6.923 7.033 6.912 5.829 5.803 5.796 5.769 5.532 5.509 5.319 5.293 5.088 5.047 5.021 4.760 4.743 4.365 4.338 4.238 4.213 4.189 4.154 4.133 4.108 4.086 4.059 4.017 4.008 3.953 3.922 3.889 3.783 3.754 3.695 3.589 3.550 3.455 3.433 3.413 3.224 3.217 3.194 2.896 2.856 2.769 2.738 2.254 1.139 1.049 0.902 0.785 0.569 19 66.13 19.43 2.06 3.20 0.95 1.10 1.07 1.95 3.14 1.00 1.14 1.03 1.01 14.64 1.00 1.10 0.88 1.00 9.48 7.24 7.02 3.48 2.99 8 7 6 5 4 3 2 1 PPM S79
S80
S81
S82
7.524 7.286 7.251 7.238 7.136 7.113 6.949 6.936 6.774 6.745 5.907 5.288 5.104 5.005 4.837 4.651 4.538 4.318 4.197 4.173 4.133 4.077 4.044 4.007 3.897 3.683 3.345 2.876 2.862 2.836 2.828 2.745 2.717 1.576 1.379 1.359 1.174 1.071 1.010 0.857 0.837 0.768 0.639 21 84.05 35.86 29.00 2.98 2.08 2.96 0.95 0.88 2.00 0.76 0.73 9.10 6.15 3.11 3.04 2.88 3.00 3.01 7 6 5 4 3 2 1 PPM PDF 文件以 "FinePrint pdffactory Pro" 试用版创建 http://www.pdffactory.com S83
S84
7.360 7.352 7.310 7.304 7.174 7.153 7.118 6.779 6.750 5.093 4.976 4.940 5.881 4.884 4.869 4.802 4.790 5.299 4.772 4.678 4.661 4.639 4.570 4.563 4.530 4.516 4.507 4.448 4.419 4.407 4.322 4.289 4.152 3.930 3.880 3.853 3.831 3.740 3.703 3.679 3.545 3.508 3.481 3.401 1.748 1.684 1.603 1.548 1.343 1.321 1.256 1.238 1.090 0.934 0.867 0.846 0.765 0.000 84.04 38.12 34.24 18.28 2.00 0.93 1.00 1.70 5.90 8 7 6 5 4 3 2 1 0 PPM S85
S86
7.370 7.314 7.134 7.123 6.801 6.784 6.776 5.305 5.297 5.106 5.069 5.893 4.999 4.970 4.955 4.875 4.851 4.840 4.816 4.746 4.700 4.577 4.557 4.538 4.519 4.447 4.418 4.402 4.319 4.224 4.200 4.134 4.115 4.036 3.847 3.829 3.790 3.706 3.620 3.492 3.386 3.342 2.885 2.804 2.776 2.703 1.636 1.410 1.356 1.337 1.261 1.226 1.090 0.906 0.866 0.845 0.759 0.007 91.70 49.23 39.75 11.95 12.05 6.75 4.06 6.03 5.01 1.00 1.20 1.16 3.22 8 7 6 5 4 3 2 1 0 PPM S87
7.358 7.321 7.160 7.131 5.847 5.011 4.990 4.974 4.914 5.290 4.753 4.646 4.610 4.589 4.574 4.548 4.497 4.456 4.437 4.398 4.284 4.243 4.118 4.090 4.062 4.030 3.835 3.807 3.795 3.763 3.723 3.674 3.654 3.600 3.590 3.502 3.415 3.394 3.389 2.607 2.581 2.533 1.349 1.305 1.254 1.229 1.138 1.090 1.009 0.952 0.936 0.868 0.853 0.752 0.000 81.91 68.14 15.98 5.08 0.74 1.74 3.22 3.67 5.45 1.00 9.64 3.37 5.07 7 6 5 4 3 2 1 PPM S88
7.338 7.315 7.294 7.285 7.200 7.190 7.163 7.149 7.132 7.122 7.108 7.084 5.726 4.859 5.486 5.300 4.847 4.821 4.750 4.726 4.647 4.621 4.598 4.581 4.531 4.507 4.496 4.467 4.417 4.381 4.289 4.201 3.988 3.979 3.845 3.576 3.559 3.543 3.516 3.429 1.336 1.565 1.253 1.230 1.197 1.173 1.149 1.125 1.096 1.079 0.913 0.902 0.880 0.855 0.730 0.000 67.92 1.15 1.09 0.96 1.00 1.08 6.67 8.83 2.37 1.28 1.00 3.08 8 7 6 5 4 3 2 1 0 PPM S89
7.356 7.321 7.261 7.238 7.177 7.155 7.133 7.121 7.109 5.664 5.345 5.072 4.961 4.923 4.764 4.651 4.587 4.578 4.548 4.536 4.527 4.500 4.312 3.814 3.598 3.533 3.351 3.248 2.884 2.539 2.362 1.660 1.631 1.606 1.600 1.372 1.332 1.284 1.255 1.180 1.153 1.127 1.104 0.989 0.964 0.903 0.879 0.855 0.829 0.730-0.002 0.98 3.28 3.30 1.81 4.34 7 6 5 4 3 2 1 0 PPM S90
S91
S92
S93