ࡱ> y{xM @zbjbj== "WWfUl,,,,,,,@4@ #........< > > > > > > $# %b a,.....b X,,.."XXX. ,.,.< X.< XX< ,,< ." `,@< < "0 #< o'o'< X@@,,,,Supporting Information Monomer synthesis: (2-Hydroxy-1-isobutyl-pent-4-enyl)-carbamic acid 9H-fluoren-9-ylmethyl ester (3): To a stirred solution of Boc-L-Leu-OMe (1.3 g, 5.3 mmole) in toluene (9 mL) at 78 (C was added DIBAL-H (1.5 M in toluene, 8.8 mL, 13.2 mmole) dropwise over 30 minutes. The reaction was stirred for 30 minutes, then quenched by slow addition of MeOH (1.0 mL, 26.3 mmole), and then warmed to room temperature. Rochelles salt (7.4 g, 26.3 mmole) in water (30 mL) was added, and the mixture was stirred for 1 hour. The mixture was filtered, extracted with Et2O (30 mL), dried over MgSO4, filtered, and concentrated under vacuum to give crude aldehyde (S)-6 (1.17 g, 103%). To a stirred solution of (+) Ipc2BOMe (1.6 g, 5 mmole) in ether (5.0 mL) at 78 (C was added dropwise allyl magnesium bromide (1.0 M in Et2O, 5.0 mL, 5.0 mmole). The reaction was stirred for 15 minutes at 78 (C, then allowed to warm to room temperature and stirred for 1 hour, during which time a white precipitate formed. The reaction was cooled to 78 (C, and aldehyde (S)-6 in Et2O (5.3 mL) was added slowly. The reaction was stirred for 3 hours, then allowed to warm to room temperature and quenched with 3N NaOH (aq.) (5 mL) and 30% H2O2 (1.7 mL). The mixture was stirred for 2 hours, then extracted with Et2O, washed with water, and brine, dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (6:1 hexanes:EtOAc to 4:1 hexanes:EtOAc) and concentrated under vacuum, then heated under high vacuum at 120 (C for 30 minutes to distill out most of the 3-pinanol byproduct, giving 0.82 g of compound (S,S)-7 (64%). The expected stereochemistry of the major product was confirmed by 1H NMR in CDCl3 by comparison with published data (J. Org. Chem. 1997, 62, 4293-4301.). The ratio of (S,S)-7 and (S,R)-7 (92:8) was determined by 1H NMR in C6D6 based on the integration of the protons on N (d = 4.55 ppm for (S,S)-7 and 4.3 ppm for (S,R)-7) and C1 (d = 3.3 ppm for (S,S)-7 and 3.5 ppm for (S,R)-7. To (S,S)-7 was added CH2Cl2 (6.4 mL) and trifluoroacetic acid (6.4 mL). The solution was stirred for 30 minutes, then concentrated under vacuum. To the residue was added dioxane (4.0 mL), water (4.0 mL), sodium carbonate (1.3 g, 12.6 mmole), and Fmoc-OSu (1.1 g, 3.2 mmole). The reaction was stirred for 14 hours, then quenched by addition of 1N HCl (aq.), extracted with Et2O, washed with water and saturated NaHCO3 (aq.), dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (2:1 Hexanes:EtOAc) to give 1.0 g (44% for 3 steps) of compound (S,S)-3 in a 97:3 mixture with (S,R)-3 (based on 1H NMR). The product could be further purified by recrystallization from hexanes/EtOAc. Allylation of aldehyde (S)-6 using(-) Ipc2BOMe followed by deprotection and reprotection gave (S,R)-3. Boc-D-Leu-OMe was used to generate (R,R)-3 and (R,S)-3. (S,S)-3: mp (157-158 (C). Rf (hexanes:EtOAc 1:1) 0.70. 1H NMR (500 MHz, CDCl3) d 7.77 (d, J = 7.3 Hz, 2H), 7.60 (d, J = 7.8 Hz, 2H), 7.41 (t, J = 7.3 Hz, 2H), 7.32 (t, J = 7.3 Hz, 2H), 5.87-5.79 (m, 1H), 5.17-5.13 (m, 2H), 4.77 (d, J = 8.8 Hz, 1H), 4.47 (d, J = 6.8 Hz, 2H), 4.22 (t, J = 6.9 Hz, 1H), 3.73 (t, J = 10.0 Hz, 1H), 3.67 (dd, J = 4.4, 8.7 Hz, 1H), 2.26-2.23 (m, 1H), 2.18-2.14 (m, 1H), 2.12 (d, J = 4.4 Hz, 1H), 1.63-1.59 (m, 1H), 1.54-1.28 (m, 2H), 0.94 (d, J = 6.4 Hz, 3H), 0.91 (d, J = 6.8 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 156.5, 143.8, 141.3, 134.6, 127.6, 127.0, 125.0, 124.9, 119.9, 118.2, 73.6, 66.3, 53.4, 47.4, 38.1, 38.0, 24.6, 23.7, 21.5; HRMS (ES+) Calcd for [C24H30NO3]+ 380.2225. Found 380.2236. (S, R)-3: Rf (hexanes:EtOAc 1:1) 0.67. 1H NMR (500 MHz, CDCl3) d 7.77 (d, J = 7.3 Hz, 2H), 7.61 (d, J = 7.8 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.32 (t, J = 7.6 Hz, 2H), 5.86-5.78 (m, 1H), 5.17-5.13 (m, 2H), 4.84 (d, J = 9.8 Hz, 1H), 4.46 (d, J = 6.8 Hz, 2H), 4.22 (t, J = 6.6 Hz, 1H), 3.74-3.68 (m, 1H), 3.63-3.60 (m, 1H), 2.29 (ddd, J = 5.4, 5.4, 14.1 Hz, 1H), 2.14 (ddd, J = 8.8, 8.8, 14.2 Hz, 1H), 1.82 (br s, 1H), 1.64-1.57 (m, 1H), 1.53 (ddd, J = 5.4, 9.8, 14.2, 1H), 1.31 (ddd, J = 4.4, 8.3, 13.2 Hz, 1H), 0.93 (d, J = 6.3 Hz, 3H), 0.92 (d, J = 6.3 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 156.6, 143.9, 141.3, 134.4, 127.6, 127.0, 125.0, 119.9, 118.5, 72.4, 66.3, 52.4, 47.3, 41.9, 39.0, 24.7, 23.2, 22.1; HRMS (ES+) Calcd for [C24H30NO3]+ 380.2225. Found 380.2210. Silyl tethering: 3-({1-[1-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-methyl-butyl]-but-3-enyloxy}-dimethyl-silanyloxy)-2-isobutyl-pent-4-enethioic acid S-benzyl ester (2): To a stirred solution of distilled dichlorodimethylsilane (1.35 mL, 11.2 mmole) in pyridine (5.6 mL) was added slowly monomer (R,S)-4 (156 mg, 0.56 mmole) in pyridine (5.6 mL). The reaction was stirred for 1 hour, then concentrated under high vacuum to remove pyridine and excess dichlorodimethylsilane. To the residue was added compound (R,R)-3 (255 mg, 0.67 mmole) in pyridine (6.7 mL). The reaction was stirred for 1 hour, then concentrated under high vacuum. The residue was dissolved in Et2O (25 mL), washed with water (2x) and saturated NaHCO3 (aq.), dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (10:1 hexanes:EtOAc to 6:1 hexanes:EtOAc) to yield 220 mg (55%) of compound (R,R,R,S-2). The procedure was repeated with all permutations of 3 and 4 to give 16 stereoisomers of 2. (R,R,R,S)-2: Rf (hexanes:EtOAc 4:1) 0.54. 1H NMR (500 MHz, CDCl3) d 7.76 (d, J = 7.8 Hz, 2H), 7.60 (dd, J = 2.0, 7.8 Hz, 2H), 7.39 (t, J = 7.3 Hz, 2H), 7.30 (t, J = 7.3 Hz, 2H), 7.28-7.19 (m, 5H), 5.84 (ddd, J = 7.3, 10.3, 17.6 Hz, 1H), 5.76 (dddd, J = 7.3, 10.2, 14.6, 17.5 Hz, 1H), 5.18 (d, J = 9.8 Hz, 1H), 5.13 (d, J = 17.1 Hz, 1H), 5.10-5.06 (m, 3H), 4.43 (dd, J = 6.9, 10.3 Hz, 1H), 4.36-4.30 (m, 2H), 4.24 (t, 6.9 Hz, 1H), 4.10 (d, J = 13.7 Hz, 1H), 4.06 (d, J = 14.2 Hz, 1H), 3.91 (ddd, J = 2.5, 7.3, 7.3 Hz, 1H), 3.73 (ddd, J = 2.4, 4.9, 11.7 Hz 1H), 2.83 (ddd, J = 3.9, 6.9, 10.8 Hz, 1H), 2.27 (ddd, J = 7.4, 7.4, 14.4 Hz, 1H), 2.19 (ddd, J = 6.8, 6.8, 14.1 Hz, 1H), 1.68 (ddd, J = 4.4, 10.8, 13.7 Hz, 1H), 1.64-1.58 (m, 1H), 1.56-1.50 (m, 1H), 1.42-1.31 (m, 2H), 1.22 ( ddd, J = 2.9, 10.8, 13.7 Hz, 1H), 0.92 (d, J = 6.8 Hz, 3H), 0.89 (d, J = 6.3 Hz, 3H), 0.84 (d, J = 6.3 Hz, 3H), 0.83 (d, J = 6.3 Hz, 3H), 0.11 (s, 3H), 0.10 (s, 3H); HRMS (ES+) Calcd for [C42H56NO5SSi]+ 714.3648. Found 714.3666. (R,R,S,R)-2: Rf (hexanes:EtOAc 4:1) 0.54. 1H NMR (500 MHz, CDCl3) d 7.76 (d, J = 7.3 Hz, 2H), 7.60 (d, J = 7.8 Hz, 2H), 7.39 (t, J = 7.3 Hz, 2H), 7.30 (ddd, J = 1.0, 7.3, 7.3 Hz, 2H), 7.27-7.20 (m, 5H), 5.80-5.73 (m, 2H), 5.38 (d, J = 9.8 Hz, 1H), 5.14-5.04 (m, 4H), 4.44-4.37 (m, 2H), 4.30 (t, J = 6.6 Hz, 1H), 4.24 (t, J = 7.1 Hz, 1H), 4.10 (d, J = 14.2 Hz, 1H), 4.06 (d, J = 13.6 Hz, 1H), 3.90 (ddd, J = 2.4, 5.4, 7.8 Hz, 1H), 3.74 (ddd, J = 2.0, 9.8, 9.8 Hz, 1H), 2.82 (ddd, J = 3.4, 6.4, 10.3 Hz, 1H), 2.27 (ddd, J = 7.3, 7.3, 14.1 Hz, 1H), 2.14 (ddd, J = 7.3, 7.3, 13.7 Hz, 1H), 1.74 (ddd, J = 4.4, 10.7, 13.7 Hz, 1H), 1.66-1.62 (m, 1H), 1.57-1.52 (m, 1H), 1.46 (ddd, J = 3.4, 11.7, 14.6 Hz, 1H), 1.37 (ddd, J = 3.4, 9.8, 13.2 Hz, 1H), 1.23 (ddd, J = 2.5, 10.3, 13.2 Hz, 1H), 0.93 (d, J = 6.4 Hz, 3H), 0.89 (d, J = 6.4 Hz, 3H), 0.87-0.84 (m, 6H), 0.11 (s, 3H), 0.07 (s, 3H); HRMS (ES+) Calcd for [C42H56NO5SSi]+ 714.3648. Found 714.3668. (R,R,R,R)-2: Rf (hexanes:EtOAc 4:1) 0.54. 1H NMR (500 MHz, CDCl3) d 7.73 (d, J = 7.3 Hz, 2H), 7.62 (dd, J = 7.8, 12.2 Hz, 2H), 7.39 (t, J = 7.5 Hz, 2H), 7.32-7.21 (m, 7H), 5.77-5.68 (m, 2H), 5.58 (d, J = 9.3 Hz, 1H), 5.19-5.15 (m, 2H), 5.10-5.06 (m, 2H), 4.51 (dd, J = 6.9, 10.3 Hz, 1H), 4.38 (t, J = 7.8 Hz, 1H), 4.30-4.22 (m, 2H), 4.14 (s, 2H), 3.90 (ddd, J = 2.4, 6.8, 6.8 Hz, 1H), 3.73 (ddd, J = 2.4, 9.7, 9.7 Hz, 1H), 2.81 (ddd, J = 3.4, 8.8, 11.7 Hz, 1H), 2.26-2.15 (m, 2H), 1.68-1.63 (m, 1H), 1.58 (ddd, J = 3.9, 11.2, 13.7 Hz, 1H), 1.51-1.43 (m, 2H), 1.20 (ddd, J = 2.9, 10.7, 13.6 Hz, 1H), 1.10 (ddd, J = 4.2, 10.6, 13.7 Hz, 1H), 0.92 (d, J = 6.9 Hz, 3H), 0.89 (d, J = 6.3 Hz, 3H), 0.80 (d, J = 6.9 Hz, 3H), 0.76 (d, J = 6.3 Hz, 3H), 0.07 (s, 3H), 0.02 (s, 3H); HRMS (ES+) Calcd for [C42H56NO5SSi]+ 714.3648. Found 714.3622. (R,R,S,S)-2: Rf (hexanes:EtOAc 4:1) 0.54. 1H NMR (500 MHz, CDCl3) d 7.77 (d, J = 7.3 Hz, 2H), 7.63 (t, J = 6.6 Hz, 2H), 7.40 (ddd, J = 2.9, 7.3, 7.3 Hz, 2H), 7.32-7.22 (m, 7H), 5.78-5.68 (m, 2H), 5.54 (d, J = 9.8 Hz, 1H), 5.18-5.06 (m, 4H), 4.50 (dd, J = 6.8, 10.7 Hz, 1H), 4.33-4.28 (m, 2H), 4.25 (t, J = 6.8 Hz, 1H), 4.20 (d, J = 13.7 Hz, 1H), 4.11 (d, J = 14.1 Hz, 1H), 3.90 (ddd, J = 2.0, 8.3, 8.3 Hz, 1H), 3.75 (ddd, J = 2.0, 9.7, 9.7 Hz, 1H), 2.82 (ddd, J = 3.4, 8.3, 11.3 Hz, 1H), 2.27 (ddd, J = 7.3, 7.3, 14.1 Hz, 1H), 2.20 (ddd, J = 6.7, 6.7, 10.4 Hz, 1H), 1.69-1.67 (m, 1H), 1.62-1.56 (m, 1H), 1.52-1.44 (m, 2H), 1.23 (ddd, J = 2.9, 10.8, 13.7 Hz, 1H), 1.12 (ddd, J = 3.4, 9.8, 13.7 Hz, 1H), 0.94 (d, J = 6.8 Hz, 3H), 0.91 (d, J = 6.4 Hz, 3H), 0.83 (d, J = 6.4 Hz, 3H), 0.80 (d, J = 6.8 Hz, 3H), 0.052 (s, 3H), 0.049 (s, 3H); HRMS (ES+) Calcd for [C42H56NO5SSi]+ 714.3648. Found 714.3616. (R,S,S,S)-2: Rf (hexanes:EtOAc 4:1) 0.54. 1H NMR (500 MHz, CDCl3) d 7.77 (d, J = 7.3 Hz, 2H), 7.65 (dd, J = 7.8, 11.7 Hz, 2H), 7.40 (t, J = 7.6 Hz, 2H), 7.31-7.20 (m, 7H), 5.81-5.69 (m, 2H), 5.27 (d, J = 9.8 Hz, 1H), 5.19-5.18 (m, 2H), 5.16-5.06 (m, 2H), 4.43 (dd, J = 7.3, 10.8 Hz, 1H), 4.40-4.35 (m, 2H), 4.22 (t, J = 7.1 Hz, 1H), 4.15 (AB q, J = 13.7 Hz, 2H), 3.77 (ddd, J = 4.9, 8.8, 8.8 Hz, 1H), 3.71 (t, J = 7.1 Hz, 1H), 2.81 (ddd, J = 2.9, 8.3, 10.8 Hz, 1H), 2.25-2.21 (m, 2H), 1.64-1.56 (m, 2H), 1.49 (ddd, J = 5.8, 9.2, 13.6 Hz, 1H), 1.28-1.21 (m, 2H), 1.14 (ddd, J = 3.4, 10.2, 13.6 Hz, 1H), 0.94 (d, J = 6.8 Hz, 3H), 0.93 (d, J = 6.4 Hz, 3H), 0.89 (d, J = 6.3 Hz, 3H), 0.88 (d, J = 6.9 Hz, 3H), 0.07 (s, 3H), 0.04 (s, 3H); HRMS (ES+) Calcd for [C42H56NO5SSi]+ 714.3648. Found 714.3617. (R,S,R,R)-2: Rf (hexanes:EtOAc 4:1) 0.54. 1H NMR (500 MHz, CDCl3) d 7.77 (d, J = 7.4 Hz, 2H), 7.64 (d, J = 7.8 Hz, 2H), 7.40 (t, J = 7.3 Hz, 2H), 7.33-7.22 (m, 7H), 5.81-5.70 (m, 2H), 5.21-5.05 (m, 5H), 4.43-4.41 (m, 2H), 4.38 (t, J = 7.5 Hz, 1H), 4.24 (t, J = 7.3 Hz, 1H), 4.19 (d, J = 13.7 Hz, 1H), 4.11 (d, J = 13.7 Hz, 1H), 3.77 (dddd, J = 1.0, 4.9, 8.8, 8.8 Hz, 1H), 3.71 (ddd, J = 1.0, 6.6, 6.8, 1H), 2.81 (dd, J = 3.0, 8.3, 11.3), 2.26-2.22 (m, 2H), 1.64-1.53 (m, 3H), 1.43 (ddd, J = 5.9, 9.3, 14.2 Hz, 1H), 1.21 (ddd, J = 5.3, 7.8, 13.6 Hz, 1H), 1.15 (ddd, J = 3.5, 9.8, 13.2 Hz, 1H), 0.94 (d, J = 6.3 Hz, 3H), 0.92 (d, J = 6.9 Hz, 3H), 0.88 (d, J = 6.3 Hz, 3H), 0.85 (d, J = 6.9Hz, 3H), 0.08 (s, 3H), 0.05 (s, 3H); HRMS (ES+) Calcd for [C42H56NO5SSi]+ 714.3648. Found 714.3662. (R,S,S,R)-2: Rf (hexanes:EtOAc 4:1) 0.54. 1H NMR (500 MHz, CDCl3) d 7.78 (d, J = 7.8 Hz, 2H), 7.62 (d, J = 7.3 Hz, 2H), 7.41 (t, J = 7.3 Hz, 2H), 7.32 (ddd, J = 1.0, 7.3, 7.3 Hz, 2H), 7.29-7.22 (m, 5H), 5.85-5.76 (m, 2H), 5.15-5.06 (m, 4H), 4.95 (d, J = 9.7 Hz, 1H), 4.43 (d, J = 7.3 Hz, 2H), 4.33 (t, J = 6.6 Hz, 1H), 4.24 (t, J = 6.8 Hz, 1H), 4.15 (d, J = 13.7 Hz, 1H), 4.09 (d, J = 13.7 Hz, 1H), 3.79-3.75 (m, 2H), 2.81 (ddd, J = 3.4, 6.3, 10.2 Hz, 1H), 2.24 (t, J = 6.5 Hz, 2H), 1.73 (ddd, J = 4.3, 10.7, 13.7 Hz, 1H), 1.60-1.55 (m, 2H), 1.46-1.37 (m, 2H), 1.23 (ddd, J = 5.4, 8.3, 13.7 Hz, 1H), 0.93 (d, J = 6.8 Hz, 3H), 0.92 (d, J = 6.8 Hz, 3H), 0.89 (d, J = 6.8 Hz, 6H), 0.12 (s, 3H), 0.11 (s, 3H); HRMS (ES+) Calcd for [C42H56NO5SSi]+ 714.3648. Found 714.3680. (R,S,R,S)-2: Rf (hexanes:EtOAc 4:1) 0.54. 1H NMR (500 MHz, CDCl3) d 7.77 (d, J = 7.8 Hz, 2H), 7.63 (dd, J = 5.4, 7.3 Hz, 2H), 7.40 (t, J = 7.6 Hz, 2H), 7.31 (t, J = 7.3 Hz, 2H), 7.29-7.21 (m, 5H), 5.85-5.76 (m, 2H), 5.15 (d, J = 17 Hz, 1H), 5.11-5.04 (m, 4H), 4.43-4.41 (m, 2H), 4.36 (t, J = 6.6 Hz, 1H), 4.23 (t, J = 6.8 Hz, 1H), 4.17 (d, J = 13.6 Hz, 1H), 4.08 (d, J = 13.6 Hz, 1H), 3.79-3.63 (m, 2H), 2.82 (ddd, J = 3.4, 5.8, 9.7 Hz, 1H), 2.24 (t, J = 7.1 Hz, 2H), 1.75 (ddd, J = 4.4, 10.8, 13.7 Hz, 1H), 1.62-1.56 (m, 2H), 1.46 (ddd, 5.9, 9.3, 13.7 Hz, 1H), 1.38 (ddd, J = 3.4, 9.2, 13.2 Hz, 1H), 1.22 (ddd, J = 5.4, 8.3, 13.7 Hz, 1H), 0.94 (d, J = 6.9 Hz, 3H), 0.92 (d, J = 6.8 Hz, 3H), 0.90 (d, J = 6.8 Hz, 3H), 0.84 (d, J = 6.8 Hz, 3H), 0.11 (s, 6H); HRMS (ES+) Calcd for [C42H56NO5SSi]+ 714.3648. Found 714.3667. Ring closing metathesis and deprotection: 8-(9H-Fluoren-9-ylmethoxycarbonylamino)-3,7-dihydroxy-2-isobutyl-10-methyl-undec-4-enethioic acid S-benzyl ester (1): To compound (R,R,R,S)-2 (117 mg, 0.16 mmole) was added Cl2(PCy3)(IMes)Ru=CHPh (14 mg, 0.016 mmole) in toluene (6.4 mL) at room temperature. The reaction was heated to 95 (C for 1h, cooled to room temperature, and concentrated under vacuum. The residue was purified by flash chromatography (12:1 hexanes:EtOAc to 8:1 hexanes:EtOAc) and concentrated under vacuum to give 98 mg (89%) of RCM product (R,R,R,S)-8, which was dissolved in THF (1.4 mL) and cooled to 0 (C. HF/pyridine (60 (L, 2.1 mmole) was added, and the solution was stirred for 30 minutes. The reaction was quenched by addition of saturated NaHCO3 (aq.), extracted with CH2Cl2 (2 x 5 mL), dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (4:1 hexanes:EtOAc to 2:1 hexanes:EtOAc) to give 79 mg (77% for 2 steps) of compound (R,R,R,S)-1. The procedure was repeated for the other stereoisomers of 2 to give 16 stereoisomers of 1. (R,R,R,S)-1: Rf (hexanes:EtOAc 1:1) 0.54. 1H NMR (500 MHz, CDCl3) d 7.76 (d, J = 7.3 Hz, 2H), 7.59 (d, J = 7.3 Hz, 2H), 7.40 (t, J = 7.3 Hz, 2H), 7.31 (t, J = 7.3Hz, 2H), 7.27-7.21 (m, 5H), 5.60-5.53 (m, 2H), 4.83 (d, J = 9.2 Hz, 1H), 4.53 (t, J = 6.5 Hz, 1H), 4.47-4.41 (m, 2H), 4.20 (t, J = 6.5 Hz, 1H), 4.11 (d, J = 13.7 Hz, 1H), 4.07 (d, J = 13.7 Hz, 1H), 3.70 (t, J = 9.8 Hz, 1H), 3.60 (d, J = 3.0 Hz, 1H), 2.83 (ddd, J = 3.9, 6.4, 10.3 Hz, 1H), 2.63 (br s, 1H), 2.37 (br s, 1H), 2.23 (t, J = 6.3 Hz, 2H), 1.77 (ddd, J = 3.9, 10.7, 14.1 Hz, 1H), 1.62-1.56 (m, 2H), 1.50 (ddd, J = 3.4, 10.3, 13.2 Hz, 1H), 1.40-1.28 (m, 2H), 0.94-0.83 (m, 12H); 13C NMR (100 MHz, CDCl3) d 201.7, 156.6, 144.0, 143.9, 141.4, 137.2, 131.6, 129.6, 128.7, 128.5, 127.6, 127.2, 127.0, 124.9, 119.9, 74.1, 69.1, 66.6, 58.3, 54.2, 47.6, 38.8, 37.8, 33.5, 32.1, 26.2, 24.9, 23.5, 21.9, 21.7; HRMS (ES+) Calcd for [C38H48NO5S]+ 630.3253. Found 630.3281. (R,R,S,R)-1: Rf (hexanes:EtOAc 1:1) 0.46. 1H NMR (500 MHz, CDCl3) d 7.76 (d, J = 7.3 Hz, 2H), 7.59 (dd, J = 4.9, 6.8 Hz, 2H), 7.40 (t, J = 7.3 Hz, 2H), 7.32 (t, J = 7.6 Hz, 2H), 7.29-7.21 (m, 5H), 5.68 (t, J = 9.6 Hz, 1H), 5.58 (ddd, J = 6.4, 9.8, 9.8 Hz, 1H), 4.82 (d, J = 8.8 Hz, 1H), 4.59-4.43 (m, 3H), 4.21 (t, J = 6.4 Hz, 1H), 4.11 (s, 2H), 3.70 (t, J = 9.3 Hz, 1H), 3.56 (d, J = 8.8 Hz, 1H), 3.21 (br s, 1H), 3.09 (br s, 1H), 2.83 (ddd, J = 3.9, 6.8, 10.8 Hz, 1H), 2.34 (ddd, J = 9.8, 14.2, 14.2 Hz, 1H), 1.96 (dd, J = 3.9, 13.7 Hz, 1H), 1.74 (ddd, J = 3.9, 10.7, 13.6 Hz 1H), 1.62-1.54 (m, 2H), 1.50 (ddd, J = 3.4, 9.8, 13.2 Hz, 1H), 1.35 (ddd, J = 3.9, 11.3, 14.7 Hz, 1H), 1.30 1.26 (m, 1H), 0.94-0.88 (m, 12 H); 13C NMR (100 MHz, CDCl3) d 200.9, 156.7, 143.94, 143.88, 141.4, 137.3, 132.3, 129.9, 128.7, 128.5, 127.6, 127.1, 127.0, 124.8, 119.9, 73.6, 68.4, 66.7, 58.0, 54.3, 47.6, 38.8, 38.0, 33.5, 31.6, 26.2, 25.0, 23.7, 23.6, 21.9, 21.7; HRMS (ES+) Calcd for [C38H48NO5S]+ 630.3253. Found 630.3240. (R,R,R,R)-1: Rf (hexanes:EtOAc 1:1) 0.50. 1H NMR (500 MHz, CDCl3) d 7.75 (d, J = 7.3 Hz, 2H), 7.58 (d, J = 6.9 Hz, 2H), 7.39 (t, J = 7.3 Hz, 2H), 7.30 (ddd, J = 1.0, 7.3, 7.3 Hz, 2H), 7.27-7.21 (m, 5H), 5.64 (ddd, J = 7.3, 7.3, 10.7 Hz, 1H), 5.50 (t, J = 9.3 Hz, 1H), 4.79 (d, J = 8.8 Hz, 1H), 4.52 (t, J = 7.4 Hz, 1H), 4.44 (d, J = 6.9 Hz, 2H), 4.19 (t, J = 6.3 Hz, 1H), 4.17 (d, J = 13.7 Hz, 1H), 4.12 (d, J = 13.7 Hz, 1H), 3.70 (m, 1H), 3.63 (br s, 1H), 2.82 (ddd, J = 6.8, 6.8, 14.2 Hz, 1H), 2.63 (br s, 2H), 2.23 (ddd, J = 4.8, 7.8, 14.1 Hz, 1H), 2.20 (ddd, J = 7.8, 7.8, 14.2 Hz, 1H), 1.67-1.54 (m, 3H), 1.36-1.25 (m, 3H), 0.91 (d, J = 6.8 Hz, 3H), 0.88 (d, J = 6.4 Hz, 6H), 0.85 (d, J = 6.3 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 202.1, 156.8, 143.99, 143.95, 141.5, 137.3, 132.5, 129.5, 128.8, 128.6, 127.7, 127.2, 127.1, 124.9, 119.9, 74.1, 69.3, 66.6, 58.0, 54.1, 47.5, 38.8, 38.6, 33.4, 32.1, 25.8, 24.8, 23.6, 23.2 21.9, 21.6; HRMS (ES+) Calcd for [C38H48NO5S]+ 630.3253. Found 630.3266. (R,R,S,S)-1: Rf (hexanes:EtOAc 1:1) 0.43. 1H NMR (500 MHz, CDCl3) d 7.75 (d, J = 7.3 Hz, 2H), 7.58 (t, J = 6.4 Hz, 2H), 7.39 (t, J = 7.3 Hz, 2H), 7.31 (t, J = 7.3 Hz, 2H), 7.27-7.20 (m, 5H), 5.65 (ddd, J = 5.4, 9.8, 9.8 Hz, 1H), 5.58 (t, J = 9.8 Hz, 1H), 4.76 (d, J = 8.8 Hz, 1H), 4.51-4.43 (m, 3H), 4.21-4.18 (m, 2H), 4.12 (d, J = 13.7 Hz, 1H), 3.68 (dd, J = 8.8, 10.7 Hz, 1H), 3.57 (d, J = 8.3 Hz, 1H), 3.18 (br s, 1H), 2.92 (br s, 1H), 2.80 (ddd, J = 3.9, 8.3, 10.8 Hz, 1H), 2.36 (ddd, J = 9.7, 9.7, 13.7 Hz, 1H), 2.02 (dd, J = 2.9, 13.1 Hz, 1H), 1.67-1.55 (m, 3H), 1.36 (ddd, J = 3.4, 11.2, 14.2 Hz, 1H), 1.29-1.24 (m, 1H), 1.18 (ddd, J = 3.9, 9.2, 13.1 Hz, 1H), 0.93-0.84 (m, 12H); 13C NMR (100 MHz, CDCl3) d 201.6, 156.6, 144.0, 143.9, 141.4, 137.3, 133.0, 130.1, 128.7, 128.5, 127.6, 127.1, 127.0, 124.9, 124.8, 119.9, 73.6, 68.7, 66.6, 57.9, 54.2, 47.6, 38.7, 38.6, 33.5, 31.7, 26.0, 24.9, 23.7, 23.5, 22.0, 21.7; HRMS (ES+) Calcd for [C38H48NO5S]+ 630.3253. Found 630.3224. (R,S,S,S)-1: Rf (hexanes:EtOAc 1:1) 0.61. 1H NMR (500 MHz, CDCl3) d 7.77 (t, J = 6.6 Hz, 2H), 7.64 (t, J = 7.8 Hz, 2H), 7.40 (ddd, J = 7.4, 7.4, 11.2 Hz, 2H), 7.34 (t, J = 7.3 Hz, 1H), 7.30 (t, J = 7.3 Hz, 1H), 7.26-71.9 (m, 5H), 5.53-5.44 (m, 2H), 4.96 (d, J = 10.3 Hz, 1H), 4.51-4.44 (m, 2H), 4.40 (dd, J = 7.3, 10.7 Hz, 1H), 4.24 (t, J = 6.6 Hz, 1H), 4.08 (d, J = 13.7 Hz, 1H), 4.03 (d, J = 13.7 Hz, 1H), 3.76-3.71 (m, 1H), 3.68 (t, J = 4.4 Hz, 1H), 3.60 (d, J = 3.4 Hz, 1H), 2.79 (ddd, J = 3.9, 8.3, 11.2 Hz, 1H), 2.53 (ddd, J = 9.7, 9.7, 13.7 Hz, 1H), 2.07 (ddd, J = 4.4, 4.4, 14.1 Hz, 1H), 1.77 (br s, 1H), 1.60-1.50, (m, 4H), 1.29-1.23 (m, 1H), 1.13 (ddd, J = 3.9, 9.8, 13.7 Hz, 1H), 0.91 (d, J = 6.4 Hz, 3H), 0.90 (d, J = 6.4 Hz, 3H), 0.87 (d, J = 6.4 Hz, 3H), 0.83 (d, J = 6.4 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 201.8, 157.3, 144.3, 143.6, 141.31, 141.25, 137.7, 133.8, 128.8, 128.4, 127.6, 127.3, 127.1, 127.0, 125.1, 125.0, 119.89, 119.86, 73.1, 68.7, 66.7, 57.4, 50.7, 47.4, 42.3, 38.4, 33.2, 25.6, 24.7, 23.7, 23.1, 22.2, 21.6; HRMS (ES+) Calcd for [C38H48NO5S]+ 630.3253. Found 630.3232. (R,S,R,R)-1: Rf (hexanes:EtOAc 1:1) 0.50. 1H NMR (500 MHz, CDCl3) d 7.78 (d, J = 7.3 Hz, 2H), 7.62 (dd, J = 4.9, 7.4 Hz, 2H), 7.41 (t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.3 Hz, 2H), 7.31-7.23 (m, 5H), 5.71 (ddd, J = 5.9, 10.7, 10.7 Hz, 1H), 5.56 (t, J = 9.8 Hz, 1H), 4.91 (d, J = 9.7 Hz, 1H), 4.51 (t, J = 8.1 Hz, 1H), 4.48-4.41 (m, 2H), 4.24 (t, J = 6.9 Hz, 1H), 4.20 (d, J = 13.7 Hz, 1H), 4.15 (d, J = 14.2 Hz, 1H), 3.73-3.69 (m, 1H), 3.59 (d, J = 8.3 Hz, 1H), 2.79 (ddd, J = 4.4, 7.3, 10.7, 1H), 2.61 (br s, 1H), 2.47 (ddd, J = 9.7, 9.7, 13.7 Hz, 1H), 2.15 (d, J = 13.6 Hz, 1H), 1.69-1.56 (m, 3H), 1.51 (ddd, J = 4.9, 9.8, 13.7, 1H), 1.31 (ddd, J = 4.4, 8.8, 13.2 Hz, 1H), 1.21 (ddd, J = 4.3, 9.2, 13.6 Hz, 1H), 0.93 (d, J = 6.8 Hz, 6H), 0.89 (d, J = 6.4 Hz, 3H), 0.85 (d, J = 6.8 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 202.2, 156.7, 144.0, 143.8, 141.3, 137.2, 132.8, 130.4, 128.8, 128.5, 127.6, 127.2, 127.0, 125.1, 125.0, 119.9, 72.3, 68.5, 66.5, 57.4, 53.4, 47.3, 41.8, 38.7, 33.4, 33.0, 25.6, 24.7, 23.5, 23.3, 22.1, 21.7; HRMS (ES+) Calcd for [C38H48NO5S]+ 630.3253. Found 630.3243. (R,S,S,R)-1: Rf (hexanes:EtOAc 1:1) 0.64. 1H NMR (500 MHz, CDCl3) d 7.78 (dd, J = 3.5, 7.9 Hz, 2H), 7.62 (t, J = 7.4 Hz, 2H), 7.42 (ddd, J = 4.4, 7.4, 7.4 Hz, 2H), 7.34 (ddd, J = 4.9, 7.4, 7.8 Hz, 2H), 7.28-7.21 (m, 5H), 5.56 (t, J = 10.3 Hz, 1H), 5.34 (ddd, J = 6.8, 14.2, 14.2 Hz, 1H), 4.99 (d, J = 9.8 Hz, 1H), 4.47 (dd, J = 6.8, 10.7 Hz, 1H), 4.41 (dd, J = 6.8, 10.7 Hz, 1H), 4.33 (t, J = 7.8 Hz, 1H), 4.24 (t, J = 6.8 Hz, 1H), 4.08 (d, J = 13.7 Hz, 1H), 4.04 (d, J = 14.2 Hz, 1H), 3.74-3.69 (m, 1H), 3.61 (br t, J = 3.4 Hz, 1H), 3.38 (d, J = 2.4 Hz, 1H), 2.78 (ddd J = 3.4, 7.8, 10.7 Hz, 1H), 2.43 (ddd, J = 9.3, 9.3, 14.1 Hz, 1H), 1.92 (dddd, J = 1.5, 4.7, 4.7, 14.2 Hz, 1H), 1.80 (d, J = 3.9 Hz, 1H), 1.60-1.46 (m, 5H), 1.30-1.24 (m, 1H), 0.92 (d, J = 6.4 Hz, 3H), 0.91 (d, J = 6.4 Hz, 3H), 0.86 (d, J = 5.9 Hz, 3H), 0.80 (d, J = 5.9 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 201.2, 157.3, 144.0, 143.6, 141.3, 137.5, 133.1, 128.8, 128.4, 127.7, 127.1, 125.0, 120.0, 119.9, 73.1, 68.2, 66.8, 57.8, 51.0, 47.3, 42.4, 38.4, 33.14, 33.09, 25.8, 24.7, 23.6, 23.2, 22.3, 21.6; HRMS (ES+) Calcd for [C38H48NO5S]+ 630.3253. Found 630.3225. (R,S,R,S)-1: Rf (hexanes:EtOAc 1:1) 0.50. 1H NMR (500 MHz, CDCl3) d 7.78 (d, J = 7.8 Hz, 2H), 7.61 (dd, J = 3.9, 7.3 Hz, 2H), 7.41 (t, J = 7.3 Hz, 2H), 7.33 (t, J = 7.3 Hz, 2H), 7.28-7.21 (m, 5H), 5.66-5.61 (m, 2H), 4.93 (d, J = 9.3 Hz, 1H), 4.50 (t, J = 6.1 Hz, 1H), 4.43 (d, J = 6.8 Hz, 2H), 4.23 (t, J = 6.8 Hz, 1H), 4.11 (d, J = 14.1 Hz, 1H), 4.06 (d, J = 14.1 Hz, 1H), 3.70-3.66 (m, 1H), 3.57 (d, J = 7.8 Hz, 1H), 2.94 (br s, 1H), 2.81 (ddd, J = 3.9, 5.9, 9.8 Hz, 1H), 2.64 ( br s, 1H), 2.44 (ddd, J = 8.8, 8.8, 14.2 Hz, 1H), 2.09 (ddd, J = 3.4, 4.9, 13.1 Hz, 1H), 1.74 (ddd, J = 4.4, 10.8, 14.7 Hz, 1H), 1.61-1.50 (m, 3H), 1.44 (ddd, J = 3.4, 9.7, 13.1 Hz, 1H), 1.30 (ddd, J = 4.9, 8.8, 13.6 Hz, 1H), 0.93 (d, J = 6.8 Hz, 6H), 0.89 (d, J = 6.3 Hz, 3H), 0.87 (d, J = 6.4 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 201.5, 156.7, 144.0, 143.8, 141.3, 137.2, 131.8, 130.1, 128.8, 128.5, 127.6, 127.2, 127.0, 125.0, 120.0, 119.9, 72.3, 68.0, 66.5, 57.4, 53.3, 47.3, 41.8, 37.6, 33.2, 33.0, 25.9, 24.7, 23.6, 23.3, 22.0, 21.6; HRMS (ES+) Calcd for [C38H48NO5S]+ 630.3253. 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