Enantioselective total synthesis of fluvirucinin B 1

Transcription

1 Enantioselective total synthesis of fluvirucinin B 1 Guillaume Guignard, Núria Llor, Elies Molins, Joan Bosch*, and Mercedes Amat* Laboratory of Organic Chemistry, Faculty of Pharmacy, and Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain Institut de Ciència de Materials (CSIC), Campus UAB, Cerdanyola, Spain Supporting Information Available I) Experimental procedures and spectroscopic data: pages S1-S17 II) III) Copies of 1 H and 13 C NMR spectra: pages S18-S48 X- ray crystallographic data for compound 18: pages S49-S59 Experimental procedures and spectroscopic data General Procedures. All air sensitive reactions were performed under a dry argon or nitrogen atmosphere with dry, freshly distilled solvents using standard procedures. Drying of organic extracts during the work-up of reactions was performed over anhydrous Na 2 SO 4 or MgSO 4. Evaporation of solvent was accomphished with a rotatory evaporator. Thin-layer chromatography was done on SiO 2 (silica gel 60 F 254 ), and the spots were located by UV and either a 1% KMnO 4 solution or hexachloroplatinate reagent. Chromatography refers to flash column chromatography and was carried out on SiO 2 (silica gel 60, mesh). Melting points were determined in a capillary tube and are uncorrected. NMR spectra were recorded at 400 MHz (1H) and MHz (13C), and chemical shifts are reported in values, in parts per million (ppm) relative to Me 4 Si (0 ppm) or relative to residual chloroform (7.26 ppm, 77.0 ppm) or benzene (7.15 ppm, ppm) as an internal standard. Data are reported in the following manner: chemical shift, multiplicity, coupling constant (J) in hertz (Hz), integrated intensity, and assignment (when possible). Assignments and stereochemical determinations are given only when they are derived from definitive two-dimensional NMR experiments (HSQC-COSY). IR spectra were performed in a spectrophotometer Nicolet Avatar 320 FT-IR and only noteworthy IR absorptions (cm -1 ) are listed. Optical rotation were measured on Perlin-Elmer 241 polarimeter. [ ] D values are given in 10-1 deg cm 2 g -1. High resolution mass spectra (HMRS) were performed by Centres Científics i Tecnològics de la Universitat de Barcelona. S1

2 5-{[(1R)-2-Hydroxy-1-phenylethyl]amino}-1-pentanol (4e): n-buli (3.56 ml of a 2.5 M solution in hexanes, 8.9 mmol) was added to a solution of NH. 3 BH 3 (275 mg, 8.9 mmol) in anhydrous THF (5 ml) at 0 ºC, and the resulting mixture was stirred at this temperature for 10 min and at room temperature for 15 minutes. Then, the mixture was added to a solution of 3e 1 (450 mg, 2.07 mmol) in anhydrous THF (10 ml), and the stirring was continued at 40 ºC for 1 h. The reaction mixture was quenched with H 2 O, and the resulting solution was extracted with Et 2 O. The combined organic extracts were dried, filtered, and concentrated. Flash chromatography (from 1:1 hexane EtOAc to 8:2 EtOAc EtOH) of the residue gave aminodiol 4e (310 mg, 67%): [ ] 22 D 54.2 (c 1.25 in CHCl 3 ); H (400 MHz; CDCl 3 ; Me 4 Si) (m, 2H, H-3), (m, 4H, H-2, H-4), (m, 2H, H-5), 3.45 (br.s, 3H, OH, NH), 3.55 (dd, J = 10.5, 8.5 Hz, 1H, CH 2 O), 3.62 (t, J = 6.4 Hz, 2H, H-1), 3.71 (dd, J = 10.5, 4.4 Hz, 1H, CH 2 O), 3.76 (dd, J = 8.5, 4.4 Hz, 1H, CH), (m, 3H, ArH), (m, 2H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 23.2 (C-3), 29.2 (C-4), 32.1 (C-2), 47.0 (C-5), 61.9 (C-1), 64.6 (CH), 66.4 (CH 2 O), (C-o), (C-p), (C-m), (C-i); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 13 H 22 NO , found (S)-5-[(tert-Butyldiphenylsilyl)oxy]-N-{(R)-2-[(tertbutyldiphenylsilyl)oxy]-1-phenylethyl}-4-ethyl-1-pentanamine (5a): tert-butyldiphenylsilyl chloride (9.1 ml, 34.8 mmol) and imidazole (3.39 g, 34.8 mmol) were added to a solution of aminodiol 4a 2 (4.18 g, 16.6 mmol) in anhydrous CH 2 Cl 2 (140 ml), and the mixture was heated at reflux for 17 h. Saturated aqueous NH 4 Cl was added, and the mixture was extracted with CH 2 Cl 2. The combined organic extracts were dried, filtered, and concentrated. The resulting residue was chromatographed (from hexane to 9:1 hexane Et 2 O) to afford pure compound 5a (9.7 g, 81%) as a colorless oil: [ ] 22 D (c 1.0 in CHCl 3 ); IR (film): = 3070, 2958, 2858, 1471, 1427, 1112 cm - 1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.82 (t, J = 7.2 Hz, 3H, CH 3 CH 2 ), 1.05 [s, 18H, 2(CH 3 ) 3 ], (m, 3H, H-2, CH 3 CH 2 ), (m, 4H, H-3, H-4, CH 3 CH 2,), 1.90 (br.s, 1H, NH), (m, 2H, H-1), 3.53 (dd, J = 4.5, 2.0 Hz, 2H, H-5), (m, 2H, CH 2 O), 3.77 (dd, J = 8.1, 4.7 Hz, 1H, CHN), (m, 5H, ArH), (m, 12H, ArH), (m, 8H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 11.2 (CH 3 CH 2 ), 19.2 and 19.3 (CMe 3 ), 23.5 (CH 3 CH 2 ), 26.8 and 26.9 [(CH 3 ) 3 ], 27.7 (C-3), 28.8 (C-2), 42.0 (C-4), 48.2 (C-1), 65.1 (CHN), 65.8 (C-5), 69.0 (CH 2 O), (CHAr), S2

3 127.5 (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (C-i), (C-i), (C-i), (C-i), (CHAr), (CHAr), (C-i); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 47 H 62 NO 2 Si , found (S)-4-Benzyl-5-[(tert-butyldiphenylsilyl)oxy]-N-{(R)-2- [(tert-butyldiphenylsilyl)oxy]-1-phenylethyl}-1-pentanamine (5b): Following the procedure described for the preparation of 5a, from aminodiol 4b 2 (510 mg, 1.63 mmol), tert-butyldiphenylsilyl chloride (0.97 ml, 3.75 mmol), and imidazole (333 mg, 4.88 mmol) in anhydrous CH 2 Cl 2 (15 ml), amine 5b was obtained (990 mg, 77%) after column chromatography (96:4 hexane EtOAc): [ ] 22 D (c 1.0 in CHCl 3 ); IR (film): = 2930, 2857, 1428, 1112 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.96 [s, 9H, (CH 3 ) 3 ], 0.99 [s, 9H, (CH 3 ) 3 ], (m, 4H, H-2, H-3), 1.58 (br.s, 1H, NH), (m, 1H, H-4), (m, 2H, H-1), 2.48 (dd, J = 13.5, 6.8 Hz, 1H, CH 2 Ar), 2.73 (dd, J = 13.5, 7.1 Hz, 1H, CH 2 Ar), 3.41 (dd, J = 10.1, 5.4 Hz, 1H, H-5), 3.48 (dd, J = 10.1, 4.5 Hz, 1H, H-5), (m, 2H, CH 2 O), (m, 1H, CHN), (m, 12H, ArH), (m, 12H, ArH), (m, 6H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 19.2 and 19.3 (CMe 3 ), 26.8 and 27.0 [(CH 3 ) 3 ], 27.7 (C-3), 28.4 (C-2), 37.6 (CH 2 Ar), 42.6 (C-4), 48.0 (C-1), 64.9 (C-5), 65.0 (CHN), 68.9 (CH 2 O), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (C-i), (C-i), (C-i), (C-i), (CHAr), (CHAr), (CHAr), (CHAr), (C-i), (C-i); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 52 H 64 NO 2 Si , found (S)-4-Benzyl-5-[(tert-butyldiphenylsilyl)oxy]-N-{(R)-2-[(tertbutyldiphenylsilyl)oxy]-1-phenylethyl}-4-ethyl-1-pentanamine (5c): Following the procedure described for the preparation of 5a, from aminodiol 4c 2 (240 mg, 0.70 mmol), tert-butyldiphenylsilyl chloride (0.37 ml, 1.41 mmol), and imidazole (144 mg, 2.11 mmol) in anhydrous CH 2 Cl 2 (6 ml), amine 5c was obtained (414 mg, 72%) after column chromatography (from hexane to 95:5 hexane EtOAc): [ ] 22 D 5.67 (c 1.15 in CHCl 3 ); IR (film): = 3070, 2930, 2857, 1471, 1428, 1112 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.86 (t, J = 7.4 Hz, 3H, CH 3 CH 2 ), 1.18 [s, 9H, (CH 3 ) 3 ], S3

4 (m, 2H, H-3), 1.27 [s, 9H, (CH 3 ) 3 ], (m, 1H, H-2), (m, 2H, H-2, CH 2 CH 3 ), (m, 1H, CH 2 CH 3 ), (m, 2H, H-1), 2.75 (d, J = 13.2 Hz, 1H, CH 2 Ar), 2.81 (d, J = 13.2 Hz, 1H, CH 2 Ar), 3.38 (d, J = 10.0 Hz, 1H, H-5), 3.42 (d, J = 10.0 Hz, 1H, H-5), (m, 2H, CH 2 O), 3.89 (dd, J = 8.0, 4.8 Hz, 1H, CHN), (m, 10H, ArH), (m, 12H, ArH), (m, 4H, ArH), (m, 4H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 7.6 (CH 3 CH 2 ), 19.2 and 19.4 (CMe 3 ), 23.7 (CH 3 CH 2 ), 25.4 (C-2), 26.9 and 27.1 [(CH 3 ) 3 ], 30.0 (C-3), 39.8 (CH 2 Ar), 41.8 (C-1), 48.5 (C-4), 65.0 (CHN), 66.1 (C-5), 68.9 (CH 2 O), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (C-i), (C-i), (C-i), (CHAr), (CHAr), (CHAr), (CHAr), (C-i); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 54 H 68 NO 2 Si , found (3R,4S)-5-[(tert-Butyldiphenylsilyl)oxy]-N- {(R)-2-[(tert-butyldiphenylsilyl)oxy]-1-phenylethyl}-3,4-(isopropylidenedioxy)-1-pentanamine (5d): Following the procedure described for the preparation of 5a, from aminodiol 4d 2 (95 mg, 0.32 mmol), tert-butyldiphenylsilyl chloride (0.17 ml, 0.64 mmol), and imidazole (22 mg, 0.97 mmol) in anhydrous CH 2 Cl 2 (3.5 ml), amine 5d was obtained (174 mg, 70%) after column chromatography (from 95:5 hexane EtOAc to EtOAc): [ ] 22 D 4.32 (c 1.35 in CHCl 3 ); IR (film): = 2930, 2857, 1428, 1112 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 1.03 [s, 9H, (CH 3 ) 3 ], 1.04 [s, 9H, (CH 3 ) 3 ], 1.82 (br.s, 2H, H-2), 2.67 (br.s, 2H, H-1), 3.60 (dd, J = 10.5, 5.1 Hz, 1H, H-5), (m, 3H, H-5, CH 2 O), 3.79 (br.s, 1H, CHN), (m, 1H, H-4), (m, 1H, H-3), (m, 5H, ArH), (m, 12H, ArH), (m, 8H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 19.1 and 19.2 (CMe 3 ), 25.5 (CH 3 ), 26.8 and 26.9 [(CH 3 ) 3 ], 28.0 (CH 3 ), 29.6 (C-2), 45.2 (C-1), 62.5 (C-5), 64.5 (CHN), 67.8 (CH 2 O), 76.5 (C-3), 77.7 (C-4), (CMe 2 ), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (C-i), (C-i), (C-i), (C-i), (CHAr); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 48 H 62 NO 4 Si , found S4

5 (R)-5-[(tert-Butyldiphenylsilyl)oxy]-N- {2-[(tert-butyldiphenylsilyl)oxy]-1-phenylethyl}-1-pentanamine (5e): Following the procedure described for the preparation of 5a, from aminodiol 4e (430 mg, 1.93 mmol), tert-butyldiphenylsilyl chloride (1.1 ml, 4.24 mmol), and imidazole (289 mg, 4.24 mmol) in anhydrous CH 2 Cl 2 (16 ml), amine 5e was obtained (890 mg, 72%) after column chromatography (from hexane to 8:2 hexane EtOAc): [ ] 22 D 13.3 (c 1.3 in CHCl 3 ); H (400 MHz; CDCl 3 ; Me 4 Si) 1.10 [s, 9H, (CH 3 ) 3 ], 1.11 [s, 9H, (CH 3 ) 3 ], 1.46 (m, 2H, CH 2 ), 1.53 (m, 2H, CH 2 ), 1.63 (m, 2H, CH 2 ), 2.52 (m, 2H, H-1), 3.71 (t, J = 6.5 Hz, 2H, H-5), 3.74 (m, 2H, CH 2 O), 3.83 (dd, J = 8.4, 4.0 Hz, 1H, CHN), (m, 4H, ArH), (m, 13H, ArH), (m, 8H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 19.2 (CMe 3 ), 23.5 (C-3), 26.8 and 26.9 [(CH 3 ) 3 ], 30.0 (C-2), 32.5 (C-4), 47.6 (C-1), 63.9 and 65.1 (C-5, CH 2 O), 68.9 (CH), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (C-i), (C-i), (C-i), (C-i), (CHAr), (C-i); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 45 H 58 NO 2 Si , found (S)-5-[(tert-Butyldiphenylsilyl)oxy]-4-ethylpentanoic acid (6a): A solution of amine 5a (2.15 g, 2.96 mmol) in CH 2 Cl 2 (5 ml) was added to a solution of m-chloroperbenzoic acid (70% of purity, 3.06 g, 12.4 mmol) in CH 2 Cl 2 (28 ml) at reflux temperature, and the resulting mixture was stirred at this temperature for 3 h. The reaction was quenched by addition of saturated aqueous NaHCO 3, and the mixture was extracted with CH 2 Cl 2. The combined organic extracts were dried, filtered, and concentrated, and the resulting residue (350 mg) was chromatographed (from 1:1 hexane CH 2 Cl 2, CH 2 Cl 2 to EtOAc) to afford the nitroso dimer 8 (420 mg) and carboxylic acid 6a (yellow oil; 930 mg, 82%). 8: IR (film): = 3070, 2857, 1589, 1495, 1471, 1427, 1211, 1104 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 1.00 [s, 9H, (CH 3 ) 3 ], 3.82 (dd, J = 10.8, 5.2 Hz, 1H, CH 2 O), 4.50 (dd, J = 10.8, 8.6 Hz, 1H, CH 2 O), 6.29 (dd, J = 8.6, 5.2 Hz, 1H, CHN), (m, 2H, ArH), (m, 2H, ArH), (m, 1H, ArH), (m, 6H, ArH), (m, 2H, ArH), (m, 2H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 19.1 (CMe 3 ), 26.7 [(CH 3 ) 3 ], 63.8 (CH 2 ), 72.4 (CHN), (CHAr), 127.7(CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (C-i), (C-i), (C-i), (CHAr), (CHAr); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 48 H 55 N 2 O 4 Si , found a: [ ] 22 D 1.96 (c 1.36 in CHCl 3 ); IR (film): = 2960, 2931, 1709 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) S5

6 0.86 (t, J = 7.3 Hz, 3H, CH 3 CH 2 ), 1.08 [s, 9H, (CH 3 ) 3 ], (m, 2H, CH 3 CH 2 ), (m, 1H, H-4), (m, 2H, H-3), (m, 2H, H-2), 3.58 (dd, J = 10.2, 5.2 Hz, 1H, H-5), 3.59 (dd, J = 10.2, 5.2 Hz, 1H, H-5), (m, 6H, ArH), (m, 4H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 11.2 (CH 3 CH 2 ), 19.3 (CMe 3 ), 23.5 (CH 3 CH 2 ), 25.9 (C-3), 26.9 [(CH 3 ) 3 ], 31.7 (C-2), 41.5 (C-4), 65.3 (C-5), (C-o), (C-p), (C-i), (C-i), (C-m), (CO); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 23 H 33 O 3 Si , found (S)-4-Benzyl-5-[(tert-butyldiphenylsilyl)oxy]pentanoic acid (6b): Operating as described in the preparation of 6a, from amine 5b (320 mg, 0.41 mmol) in CH 2 Cl 2 (1.8 ml) and m-chloroperbenzoic acid (70% of purity, 420 mg, 1.70 mmol) in CH 2 Cl 2 (4 ml), the nitroso dimer 8 (55 mg) and carboxylic acid 6b (119 mg, 66%) were obtained after flash chromatography (from 1:1 hexane CH 2 Cl 2, CH 2 Cl 2 to EtOAc). 6b: [ ] 22 D 6.91 (c 1.0 in CHCl 3 ); IR (film): = 3069, 2930, 1708 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 1.01 [s, 9H, (CH 3 ) 3 ], (m, 2H, H-3), (m, 1H, H-4), (m, 2H, H-2), 2.51 (dd, J = 13.6, 6.6 Hz, 1H, CH 2 Ar), 2.71 (dd, J = 13.6, 7.2 Hz, 1H, CH 2 Ar), 3.46 (dd, J = 4.5, 1.2 Hz, 2H, H-5), (m, 5H, ArH), (m, 6H, ArH), (m, 4H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 19.3 (CMe 3 ), 25.9 (C-3), 26.9 [(CH 3 ) 3 ], 31.7 (C-2), 37.5 (CH 2 Ar), 41.9 (C-4), 64.6 (C-5), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (C-i), (CHAr), (CHAr), (C-i), (CO); HRMS (ESI-TOF) m/z [M - H] - Calcd for C 28 H 33 O 3 Si , found (S)-4-Benzyl-5-[(tert-butyldiphenylsilyl)oxy]-4-ethylpentanoic acid (6c): Operating as described in the preparation of 6a, from amine 5c (300 mg, 0.37 mmol) in CH 2 Cl 2 (1.5 ml) and m-chloroperbenzoic acid (70% of purity, 380 mg, 1.54 mmol) in CH 2 Cl 2 (3.5 ml), the nitroso dimer 8 (57 mg) and carboxylic acid 6c (130 mg, 75%) were obtained after flash chromatography (from 1:1 hexane CH 2 Cl 2, CH 2 Cl 2 to EtOAc). 6c: [ ] 22 D (c 0.65 in CHCl 3 ); IR (film): = 3074, 2933, 2861, 1707 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.83 (t, J = 7.4 Hz, 3H, CH 3 CH 2 ), 1.19 [s, 9H, (CH 3 ) 3 ], 1.22 (q, J = 7.4 Hz, 2H, CH 3 CH 2 ), 1.54 (ddd, J = 14.0, 14.0, 5.0 Hz, 1H, H-3), 1.63 (ddd, J = 14.0, 14.0, 5.0 Hz, 1H, H-3), (m, 1H, H-2), (m, 1H, H- S6

7 2), 2.66 (d, J = 13.0 Hz, 1H, CH 2 Ar), 2.72 (d, J = 13.0 Hz, 1H, CH 2 Ar), 3.29 (d, J = 10.3 Hz, 1H, H- 5), 3.34 (d, J = 10.3 Hz, 1H, H-5), (m, 5H, ArH), (m, 6H, ArH), (m, 4H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 7.4 (CH 3 CH 2 ), 19.4 (CMe 3 ), 24.7 (CH 3 CH 2 ), 27.2 [(CH 3 ) 3 ], 27.8 (C-3), 28.4 (C-2), 39.6 (CH 2 Ar), 41.5 (C-4), 65.9 (C-5), (C-p), (CHAr), (CHAr), (CHAr), (C-p), (C-p), (CHAr), (C-i), (C-i), (CHAr), (CHAr), (C-i), (CO); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 30 H 39 O 3 Si , found (3R,4S)-5-[(tert-Butyldiphenylsilyl)oxy]3,4-(isopropylidenedioxy)pentanoic acid (6d): Operating as described in the preparation of 6a, from amine 5d (70 mg, 0.09 mmol) in CH 2 Cl 2 (0.8 ml) and m-chloroperbenzoic acid (70% of purity, 94 mg, 0.38 mmol) in CH 2 Cl 2 (1 ml), the nitroso dimer 8 (8 mg) and carboxylic acid 6d (21 mg, 54%) were obtained after flash chromatography (from 1:1 hexane CH 2 Cl 2, CH 2 Cl 2 to EtOAc). 6d: [ ] 22 D (c 0.6 in CHCl 3 ); IR (film): = 3071, 2931, 2858, 1714, 1112 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.98 [s, 9H, (CH 3 ) 3 ], 1.27 (s, 3H, CH 3 ), 1.31 (s, 3H, CH 3 ), 2.61 (dd, J = 16.1, 9.1 Hz, 1H, H-2), 2.79 (dd, J = 16.1, 4.5 Hz, 1H, H-2), (m, 2H, H-5), 4.18 (m, 1H, H-4), 4.60 (m, 1H, H-3), (m, 6H, ArH), (m, 4H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 19.1 (CMe 3 ), 25.4 (CH 3 ), 26.8 [(CH 3 ) 3 ], 27.9 (CH 3 ), 34.9 (C-2), 62.2 (C-5), 73.5 (C-3), 76.8 (C-4), (CMe 2 ), (C-o), (C-p), (C-i), (C-m), (CO); HRMS (ESI-TOF) m/z [M - H] - Calcd for C 24 H 31 O 5 Si , found [(tert-Butyldiphenylsilyl)oxy]pentanoic acid (6e). From lactam 5e: Operating as described in the preparation of 6a, from amine 5e (285 mg, 0.41 mmol) in CH 2 Cl 2 (1.5 ml) and m-chloroperbenzoic acid (70% of purity, 422 mg, 1.71 mmol) in CH 2 Cl 2 (4 ml), the nitroso dimer 8 (70 mg) and carboxylic acid 6e (103 mg, 71%) were obtained after flash chromatography (from 1:1 hexane CH 2 Cl 2, CH 2 Cl 2 to EtOAc). From nitrone 7e: UHP (202 mg, 2.09 mmol) and Na 2 WO 4.2H 2 O (8.7 mg, mmol) were added at room temperature to a solution of amine 5e (365 mg, 0.52 mmol) in 1:1 CH 2 Cl 2 methanol (3.4 ml), and the mixture was stirred at this temperature for 21 h. Solvents were removed under reduced pressure, and the S7

8 crude residue was taken up with CH 2 Cl 2. The resulting white solid was filtered, and the solvent was removed under reduced pressure to afford nitrone 7e (320 mg), which was used without purification in the next step: H (400 MHz; CDCl 3 ; Me 4 Si) 0.79 (m, 2H, H-3), 0.93 [s, 9H, (CH 3 ) 3 ], 0.96 [s, 9H, (CH 3 ) 3 ], 1.50 (br.s, 2H, H-4), 2.40 (m, 1H, H-2), 2.47 (m, 1H, H-2), 3.58 (br.s, 2H, H- 5), 3.77 (dd, J = 10.0, 4.0 Hz, 1H, CHAr), 4.57 (t, J = 10.0 Hz, 1H, CH 2 O), 4.65 (dd, J = 10.0, 4.0 Hz, 1H, CH 2 O), 6.75 (m. 1H, H-1), (m, 17H, ArH), (m, 8H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 19.1 and 19.2 (CMe 3 ), 22.1 (C-3), 26.5 (C-2), 26.7 and 26.8 [(CH 3 ) 3 ], 32.4 (C- 4), 63.4 (C-5), 63.7 (CH), 79.6 (CH 2 O), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr), (CHAr),129.5 (CHAr), (CHAr), (CHAr), (C-i), (C-i), (C-i), (C-i), (C-i), (CHAr), (CHAr), (CHAr), (C-1). Operating as described in the preparation of 6a, from crude nitrone 7e (320 mg, 0.45 mmol) in CH 2 Cl 2 (1.5 ml) and m-chloroperbenzoic acid (70% of purity, 276 mg, 1.12 mmol) in CH 2 Cl 2 (4 ml), the nitroso dimer 8 (41 mg) and carboxylic acid 6e (yellow oil; 84 mg, 45% from 5e) were obtained after flash chromatography (from 1:1 hexane CH 2 Cl 2, CH 2 Cl 2 to EtOAc). 6e: IR (film): = 3071, 2931, 2858, 1709 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 1.05 [s, 9H, (CH 3 ) 3 ], (m, 2H, H-4), (m, 2H, H-3), 2.35 (t, J = 7.6 Hz, 2H, H-2), 3.67 (t, J = 5.6 Hz, 2H, H-5), (m, 6H, ArH), (m, 4H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 19.2 (CMe 3 ), 21.1 (C-3), 26.8 [(CH 3 ) 3 ], 31.8 (C-4), 33.7 (C-2), 63.3 (C-5), (C-o), (C-p), (C-i),135.5 (C-m), (CO); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 21 H 29 O 3 Si , found (S)-5-[(tert-Butyldiphenylsilyl)oxy]-4-ethylpentanenitrile (9): 20% Aqueous solution of NH 3 (6 ml) and iodine (228 mg, 0.90 mmol) were added to a solution of amine 5a (70 mg, 0.01 mmol) in anhydrous THF (2 ml) at room temperature, and the resulting mixture was stirred at 60 ºC for 21 h. The mixture was washed with saturated aqueous Na 2 SO 3 and extracted with Et 2 O. The combined organic phases were dried, filtered, and concentrated to give an oil. Flash chromatography (from hexane to 6:4 hexane CH 2 Cl 2 ) afforded pure nitrile 9 (25 mg, 71%) as a yellow oil: [ ] 22 D (c 0.5 in CHCl 3 ); IR (film): = 2960, 1471, 1427, 1112 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.83 (t, J = 7.4 Hz, 3H, CH 3 ), 1.06 [s, 9H, (CH 3 ) 3 ], (m, 2H, CH 2 CH 3 ), (m, 1H, H-4), (m, 1H, H-3), (m, 1H, H-3), (m, 2H, H-2), 3.53 (dd, J = 10.4, 5.6 Hz, 1H, H-5), 3.59 (dd, J = 10.4, 4.4 Hz, 1H, H-5), (m, 6H, ArH), (m, 4H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 11.2 (CH 3 ), 14.9 (C-2), 19.2 (CMe 3 ), 23.3 (CH 2 ), 26.9 [(CH 3 ) 3 ], 27.1 (C-3), 41.1 (C-4), 64.9 (C-5), (CN), (C-o), S8

9 129.7 (C-p), (C-i), (C-m); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 23 H 32 NOSi , found Synthesis of fluvirucinin B 1 (R)-5-{[(1S)-2-Hydroxy-1-phenylethyl]amino}-2-ethyl-1-pentanol (ent-4a = 2) was prepared from lactam 1 3 by the same procedure as described for 4a. 2 Ent-4a: [ ] 22 D (c 0.8 in MeOH). (R)-5-[(tert-Butyldiphenylsilyl)oxy]-N-{(S)-2-[(tertbutyldiphenylsilyl)oxy]-1-phenylethyl}-4-ethyl-1-pentanamine (ent-5a) was prepared from aminodiol ent-4a operating as in the above preparation of 5a. Ent-5a: [ ] 22 D (c 1.0 in CHCl 3 ). (R)-5-[(tert-Butyldiphenylsilyl)oxy]-4-ethylpentanoic acid (ent-6a) was prepared from amine ent-5a operating as in the above preparation of carboxylic acid 6a. Ent- 6a: [ ] 22 D (c 1.38 in CHCl 3 ). (R)-5-[(tert-Butyldiphenylsilyl)oxy]-4-ethyl-1-pentanol: BH 3 -THF (3.83 ml of a 1.0 M solution in THF, 3.83 mmol) was added to a cooled (0 ºC) solution of ent-6a (490 mg, 1.28 mmol) in anhydrous THF (15 ml), and the mixture was stirred at room temperature for 4 h. The reaction was quenched with 8 ml of a 1:1 H 2 O Et 2 O mixture, poured into saturated aqueous K 2 CO 3, and extracted with Et 2 O. The combined organic extracts were dried, filtered, and concentrated. The resulting residue was purified by flash chromatography (85:15 hexane EtOAc) S9

10 to gave the title alcohol (423 mg, 90%) as a colorless oil: [ ] 22 D (c 3.9 in CHCl 3 ) {Lit 4 [ ] 23 D +2.7 (c 0.05 in CHCl 3 ); Lit 5 (for the enantiomer) [ ] 22 D 2.00 (c 3.9 in CHCl 3 )}; IR (film): = 3400, 2930, 1427, 1112 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.83 (t, J = 7.3 Hz, 3H, CH 3 ), 1.05 [s, 9H, (CH 3 ) 3 ], (m, 2H, H-3, CH 2 CH 3 ), (m, 3H, H-3, H-4, CH 2 CH 3 ), (m, 2H, H-2), 1.55 (br.s, 1H, OH), 3.56 (d, J = 4.5 Hz, 2H, H-5), 3.59 (t, J = 6.5 Hz, 2H, H-1), (m, 6H, ArH), (m, 4H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 11.2 (CH 3 ), 19.3 (CMe 3 ), 23.6 (CH 2 ), 26.6 [(CH 3 ) 3 ], 26.9 (C-3), 30.1 (C-2), 41.8 (C-4), 63.3 (C-1), 64.3 (C-5), (C-o), (C-p), (C-i), (C-m); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 23 H 35 O 2 Si , found (R)-1-[(tert-Butyldiphenylsilyl)oxy]-2-ethyl-5-iodopentane (10): Triphenylphosphine (300 mg, 1.13 mmol) and imidazole (80 mg, 1.13 mmol) were added to a solution of the above alcohol (200 mg, 0.54 mmol) in CH 2 Cl 2 (7 ml) at room temperature. Then, iodine (290 mg, 1.13 mmol) was added at 0 C, and the mixture was stirred at room temperature for 15 h. The solvent was evaporated under reduced pressure to afford a brown residue. Flash chromatography (from hexane to 95:5 hexane CH 2 Cl 2 ) of the residue gave iodide 10 (232 mg, 90%) as a colorless oil: [ ] 22 D (c 0.75 in CHCl 3 ); IR (film): = 2929, 1111 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.83 (t, J = 7.4 Hz, 3H, CH 3 ), 1.06 [s, 9H, (CH 3 ) 3 ], (m, 5H, H-2, H-3, CH 2 CH 3 ), (quint, J = 7.5 Hz, 2H, H-4), 3.13 (t, J = 7.5 Hz, 2H, H-5), 3.51 (dd, J = 10.1, 4.5 Hz, 1H, H-1), 3.55 (dd, J = 10.1, 4.8 Hz, 1H, H-1), (m, 6H, ArH), (m, 4H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 7.5 (C-5), 11.3 (CH 3 ), 19.3 (CMe 3 ), 23.6 (CH 2 ), 26.6 [(CH 3 ) 3 ], 31.1 (C-4), 31.8 (C-3), 41.3 (C-2), 65.6 (C-1), (C-o), (C-p), (C-i), (C-m); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 23 H 34 IOSi , found (R)-7-[(tert-Butyldiphenylsilyl)oxy]-6-ethyl-2-methyl-1-heptene (11): Isopropenylmagnesium bromide (3.62 ml of a 0.5 M solution in THF, 1.81 mmol) was added at 0 ºC to a suspension of iodide 10 (290 mg, 0.60 mmol) and CuI (12.6 mg, mmol) in anhydrous THF (3.5 ml), and the resulting mixture was stirred at room temperature for 2 h. Then, saturated aqueous NH 4 Cl was added, and the mixture was extracted with EtOAc. The combined organic extracts were dried, filtered, and evaporated. The resulting residue was chromatographed (hexane) to afford alkene 11 (211 mg, 89%) as a colorless oil: [ ] 22 D (c 1.05 in CHCl 3 ); IR S10

11 (film): = 2927, 1425, 1113 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.82 (t, J = 7.3 Hz, 3H, CH 3 CH 2 ), 1.05 [s, 9H, (CH 3 ) 3 ], (m, 1H, H-5), (m, 6H, H-4, H-5, H-6, CH 3 CH 2 ), 1.69 (s, 3H, CH 3 ), (brt, J = 7.0 Hz, 2H, H-3), 3.54 (d, J = 4.9 Hz, 2H, H-7), (m, 2H, H- 1), (m, 6H, ArH), (m, 4H, ArH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 11.3 (CH 3 CH 2 ), 19.3 (CMe 3 ), 22.4 (CH 3 ), 23.6 (CH 3 CH 2 ), 24.9 (C-4), 26.9 [(CH 3 ) 3 ], 30.3 (C-5), 38.2 (C-3), 42.0 (C- 6), 65.8 (C-7), (C-1), (C-o), (C-p), (C-i), (C-m), (C-2); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 26 H 39 OSi , found (R)-2-Ethyl-6-methyl-6-hepten-1-ol: Tetrabutylammonium fluoride (3.83 ml of a 1.0 M solution in THF, 3.83 mmol) was added to a solution of 11 (378 mg, 0.96 mmol) in anhydrous THF (6 ml) at 0 ºC, and the mixture was stirred at room temperature for 17 h. The solvent was eliminated under reduced pressure and the crude residue was purified by flash chromatography (from hexane to 8:2 hexane EtOAc) to give the title alcohol (187 mg, 80%) as a colorless liquid: [ ] 22 D 1.41 (c 0.7 in CHCl 3 ); IR (film): = 3336, 1649, 1460 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.90 (t, J = 7.3 Hz, 3H, CH 2 CH 3 ), (m, 2H, CH 3 CH 2 ), (m, 5H, H- 2, H-3, H-4), 1.71 (s, 3H, CH 3 ), 2.01 (t, J = 7.5 Hz, 2H, H-5), 3.55 (d, J = 5.2 Hz, 2H, H-1), (m, 2H, H-7); C (100.6 MHz; CDCl 3 ; Me 4 Si) 11.1 (CH 3 CH 2 ), 22.3 (CH 3 ), 23.3 (CH 3 CH 2 ), 24.8 (C-4), 30.0 (C-3), 38.1 (C-5), 41.9 (C-2), 65.2 (C-1), (C-7), (C-6). (R) 2-Ethyl-6-methyl-6-heptenoic acid (12): DMSO (0.46 ml, 6.47 mmol) was added to a cooled ( 78 ºC) solution of oxalyl chloride (0.27 ml, 3.23 mmol) in CH 2 Cl 2 (16 ml), and the mixture was stirred at this temperature for 10 min. Then, a solution of the above alcohol (459 mg, 2.94 mmol) in CH 2 Cl 2 (16 ml) was added, and the mixture was stirred at 78 ºC for 30 min. Triethylamine (2.05 ml, 14.7 mmol) was added and, after 40 min, the mixture was allowed to warm to room temperature and was washed with saturated NaHCO 3. The organic extract was dried, filtered, and concentrated, to give the corresponding aldehyde (460 mg) as a yellow oil, which was used without further purification: H (400 MHz; CDCl 3 ; Me 4 Si) 0.92 (t, J = 7.5 Hz, 3H, CH 3 CH 2 ), (m, 3H), (m, 1H), (m, 2H), 1.70 (s, 3H, CH 3 ), 2.02 (t, J = 7.0 Hz, 2H, H-5), (m, 1H), (m, 1H, H-7), (m, 1H, H-7), 9.58 (d, J = 3.0 Hz, 1H, CHO). A solution of NaClO 2 (3.19 g, mmol) and NaH 2 PO 4 (3.24 g, 27.0 mmol) in water (14 ml) was added to a solution of the above crude aldehyde (460 mg) and 2-methyl-2- butene (14.7 ml of a 2.0 M solution in THF, 29.4 mmol) in t-buoh (28 ml), and the mixture was S11

12 stirred at room temperature for 3 h. The reaction was quenched by addition of H 2 O, and the aqueous layer was extracted with CH 2 Cl 2. The combined organic extracts were dried, filtered, and concentrated. Flash chromatography (from 8:2 hexane CH 2 Cl 2 to CH 2 Cl 2 ) of the residue gave carboxylic acid 12 (370 mg, 74%) as a colorless liquid: [ ] 22 D 6.87 (c 1.2 in CHCl 3 ); IR (film): = 3074, 2938, 1707 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.94 (t, J = 7.4 Hz, 3H, CH 3 CH 2 ), (m, 6H, CH 3 CH 2, H-3, H-4), 1.70 (s, 3H, CH 3 ), 2.02 (brt, J = 7.0 Hz, 2H, H-5), 2.30 (m, 1H, H-2), 4.67 (br.s, 1H, H-7), 4.70 (br.s, 1H, H-7); C (100.6 MHz; CDCl 3 ; Me 4 Si) 11.7 (CH 3 CH 2 ), 22.2 (CH 3 ), 25.2 (CH 3 CH 2, C-4), 31.2 (C-3), 37.6 (C-5), 47.0 (C-2), (C-7), (C-6), (CO); HRMS (ESI-TOF) m/z [M - H] - Calcd for C 10 H 17 O , found (R)-4-(Hydroxymethyl)hexanenitrile: 20% Aqueous solution of NH 3 (196 ml) and iodine (11.59 g, 45.7 mol) were added to a solution of amine ent-5a (4.11 g, 5.65 mol) in anhydrous THF (10 ml) at room temperature, and the resulting mixture was stirred at 60 ºC for 21 h. The mixture was washed with a saturated aqueous Na 2 SO 3 and extracted with Et 2 O. The combined organic phases were dried, filtered, and concentrated to give crude ent-9 as an oil, which was used without purification in the next step. An aliquot was chromatographed (from hexane to 6:4 hexane CH 2 Cl 2 ) to give pure ent-9 {[ ] 22 D 4.00 (c 0.5 in CHCl 3 )}. Tetrabutylammonium fluoride (17.6 ml of a 1.0 M solution in THF, 17.6 mmol) was added to a solution of the above crude ent-9 (2.06 g) in anhydrous THF (36 ml) at 0 ºC, and the mixture was stirred at room temperature for 3.5 h. The solvent was eliminated under reduced pressure and the crude residue was purified by flash chromatography (from 9:1 to 1:1 hexane EtOAc) to give (R)-4- (hydroxymethyl)hexanenitrile (540 mg, 75% from ent-5a) as a yellow oil: [ ] 22 D 5.26 (c 1.25 in CHCl 3 ) {Lit 6 [ ] 22 D 7.1 (c 0.97 in CHCl 3 )}; IR (film): = 3440, 2247 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.93 (t, J = 7.5 Hz, 3H, H-6), (m, 2H, H-5), (m, 1H, H-4), (m, 2H, H-3), 2.05 (br.s, 1H, OH), (m, 2H, H-2), 3.54 (dd, J = 10.9, 6.1 Hz, 1H, CH 2 O), 3.65 (dd, J = 10.9, 4.6 Hz, 1H, CH 2 O); C (100.6 MHz; CDCl 3 ; Me 4 Si) 11.0 (C-6), 15.0 (C-2), 23.1 (C-5), 26.8 (C-3), 40.8 (C-4), 64.1 (CH 2 O), (CN); HRMS (ESI-TOF) m/z [M + NH 4 ] + Calcd for C 7 H 17 N 2 O , found (R)-4-Formylhexanenitrile (13): DMSO (0.25 ml, 3.55 mmol) was added to a cooled ( 78 ºC) solution of oxalyl chloride (0.15 ml, 1.77 mmol) in CH 2 Cl 2 (7 ml), and the mixture S12

13 was stirred at this temperature for 10 min. Then, a solution of (R)-4-(hydroxymethyl)hexanenitrile (205 mg, 1.61 mmol) in CH 2 Cl 2 (7 ml) was slowly added, and the yellow mixture was stirred at 78 ºC for 30 min. Triethylamine (1.12 ml, 8.06 mmol) was added and, after 1 h, the mixture was allowed to warm to room temperature and washed with saturated NaHCO 3. The organic layer was dried, filtered, and concentrated, and the resulting residue was chromatographed (9:1 hexane EtOAc) to afford aldehyde 13 (152 mg, 75%): [ ] 22 D +9.1 (c 0.35 in CHCl 3 ); H (400 MHz; CDCl 3 ; Me 4 Si) 0.99 (t, J = 7.5 Hz, 3H, CH 3 ), (m, 1H), (m, 2H), (m, 1H), (m, 3H, H-4, H-2), 9.67 (s, 1H, CHO); HRMS (ESI-TOF) m/z [M + NH 4 ] + Calcd for C 7 H 15 N 2 O , found (4R,5R)-4-Ethyl-5-hydroxy-7-octenenitrile (14): (S,S)-2-Allyl-1,3-bis-(4- bromobenzyl)-2-chlorooctahydro-2-1h-1,3,2-benzodiazasilole (Leighton reagent; 1.30 g, 2.30 mmol) and scandium triflate (49 mg, mmol) were added to a solution of aldehyde 13 (240 mg, 1.92 mmol) in anhydrous CH 2 Cl 2 (19 ml), and the resulting mixture was stirred at 0 ºC for 5 h, and at room temperature for 12 h. Then, a solution of tetrabutylammonium fluoride (1.9 ml, 1.9 mmol) was added, and the mixture was stirred at room temperature for 30 min. The solvent was evaporated, and the resulting residue was chromatographed (from 8:2 hexane CH 2 Cl 2 to CH 2 Cl 2 ) to give alcohol 14 together with minor amounts of 5-epi-14 (dr 9:1, 284 mg, 85% yield): IR (film): = 3468, 2247 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si, from the mixture) 0.95 (t, J = 7.5 Hz, 3H, CH 3 CH 2 ), (m, 1H), (m, 1H), (m, 3H, 2H, OH), (m, 1H), (m, 1H), (m, 1H), 2.45 (m, 2H, CH 2 CN), (m, 1H, H-5), (m, 2H, H-8), (m, 1H, H-7); C (100.6 MHz; CDCl 3 ; Me 4 Si, from the mixture) 14: 11.6 (CH 3 CH 2 ), 15.4 (CH 2 CN), 21.4 (CH 2 ), 25.5 (CH 2 ), 37.9 (CH 2 CH=CH 2 ), 43.3 (CH), 71.3 (CHOH), (CH 2 =CH), (CN), (CH 2 =CH); 5-epi-14: 11.0 (CH 3 CH 2 ), 15.2 (CH 2 CN), 22.4 (CH 2 ), 24.9 (CH 2 ), 39.5 (CH 2 CH=CH 2 ), 43.2 (CH), 71.4 (CHOH), (CH 2 =CH), (CN), (CH 2 =CH); HRMS (ESI-TOF) m/z [M + NH 4 ] + Calcd for C 10 H 21 N 2 O , found (4R,5R)-5-[(tert-Butyldimethylsilyl)oxy]-4-ethyl-7- octenenitrile: tert-butyldimethylsilyl chloride (760 mg, 5.04 mmol) and imidazole (458 mg, 6.73 mmol) were added to a solution of the above mixture of epimeric alcohols 14 (281 mg, 1.68 mmol) in CH 2 Cl 2 (5 ml). The solution was stirred at reflux temperature for 15 h. Then, saturated aqueous S13

14 NH 4 Cl was added, and the mixture was extracted with CH 2 Cl 2. The combined organic extracts were dried, filtered, and concentrated. Flash chromatography (from 9:1 to 8:2 hexane-ch 2 Cl 2 ) of the residue afforded the protected alcohol (9:1 mixture of C-5 epimers; 365 mg, 77% yield) as a colorless oil: IR (film): = 2959, 2246 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si, from the mixture) 0.05 (s, 3H, CH 3 Si), 0.06 (s, 3H, CH 3 Si), 0.89 [s, 9H, (CH 3 ) 3 ], 0.94 (t, J = 7.4 Hz, 3H, CH 3 CH 2 ), (m, 2H, CH 2 ), (m, 2H, H-4, CH 2 ), (m, 1H, CH 2 ), (m, 2H, H-6), 2.41 (t, J = 7.5 Hz, 2H, H-2), (m, 1H, H-5), (m, 2H, H-8), (m, 1H, H-7); C (100.6 MHz; CDCl 3 ; Me 4 Si, from the mixture) 5R (major epimer): 4.5 (CH 3 Si), 4.4 (CH 3 Si), 12.0 (CH 3 CH 2 ), 15.8 (C-2), 18.0 (CMe 3 ), 22.7 (CH 2 ), 25.6 (CH 2 ), 25.8 [(CH 3 ) 3 ], 37.3 (C-6), 44.4 (C-4), 73.4 (C-5), (C-8), (C-1), (C-7); 5S (minor epimer): 4.8 (CH 3 Si), 4.2 (CH 3 Si), 11.6 (CH 3 CH 2 ), 15.3 (C-2), 18.0 (CMe 3 ), 22.6 (CH 2 ), 24.8 (CH 2 ), 25.8 [(CH 3 ) 3 ], 39.5 (C-6), 42.6 (C- 4), 72.8 (C-5), (C-8), (C-1), (C-7); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 16 H 32 NOSi , found (4R,5R)-5-[(tert-Butyldimethylsilyl)oxy]-4-ethyl-7-octenamine (15): A solution of the above mixture of epimeric nitriles (345 mg, 1.23 mmol) in anhydrous Et 2 O (1.0 ml) was slowly added to a cooled (0 ºC) solution of LiAlH 4 (2.1 ml of a 1.0 M solution in THF, 2.09 mmol) in anhydrous Et 2 O (1.0 ml), and the resulting mixture was stirred at room temperature for 2 h. After cooling to 0 ºC, H 2 O (132 L), 10% aqueous NaOH (250 L), and H 2 O (573 L) were successively added. The insoluble white precipitate was removed by filtration and washed with Et 2 O. The filtrate was dried, filtered, and concentrated to give pure amine 15 (305 mg, 87%) as a colorless oil: [ ] 22 D (c 1.0 in MeOH); IR (film): = 2957, 2930, 2858 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.03 (s, 3H, CH 3 Si), 0.04 (s, 3H, CH 3 Si), (m, 3H, CH 3 CH 2 ), 0.88 [s, 9H, (CH 3 ) 3 ], (m, 7H, H-2, H-3, H-4, CH 3 CH 2 ), (m, 2H, H-6), 2.67 (t, J = 7.0 Hz, 2H, H-1), (m, 1H, H-5), (m, 2H, H-8), (dddd, J = 14.2, 10.3, 7.2, 7.2 Hz, 1H, H-7); C (100.6 MHz; CDCl 3 ; Me 4 Si) 4.7 (CH 3 Si), 4.4 (CH 3 Si), 12.1 (CH 3 CH 2 ), 17.9 (CMe 3 ), 22.3 (CH 2 ), 25.7 [(CH 3 ) 3 ], 26.3 (CH 2 ), 31.9 (CH 2 ), 37.8 (C-6), 42.5 (C-1), 44.7 (C-4), 73.4 (C-5), (C-8), (C-7); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 16 H 36 NOSi , found S14

15 (R)-N-{(4R,5R)-5-[(tert-Butyldimethylsilyl)oxy]-4-ethyl-7-octen-1-yl}-2-ethyl- 6-methyl-6-heptenamide (16): N-(3-Dimethylaminopropyl)-N -ethylcarbodiimide hydrochloride (189 mg, 0.99 mmol) was added to a cooled solution (0 ºC) of amine 15 (268 mg, 0.94 mmol) and 1-hydroxybenzotriazole (159 mg, 1.17 mmol) in anhydrous DMF (5.5 ml), and the resulting mixture was stirred at 0 ºC for 10 min. Then, a solution of carboxylic acid 12 (176 mg, 10.3 mmol) in anhydrous DMF (1.5 ml) was added, and the stirring was continued at room temperature for 15 h. The solvent was evaporated, the resulting residue was dissolved in Et 2 O, and the solution was washed with H 2 O. The organic layer was dried, filtered, and concentrated to give an oil. Flash chromatography (8:2 hexane EtOAc) afforded amide 16 (325 mg, 79%) as a colorless oil: [ ] 22 D (c 2.05 in CHCl 3 ); IR (film): = 3297, 2963, 1641, 1549, 1462 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.01 (s, 3H, CH 3 Si), 0.01 (s, 3H, CH 3 Si), (m, 15H, 2CH 3 CH 2, (CH 3 ) 3 ), (m, 1H), (m, 3H), (m, 7H), (m, 2H), 1.66 (s, 3H, CH 3 ), 1.88 (m, 1H), 1.96 (t, J = 7.0 Hz, 2H, CH 2 CH 2 =CH), (m, 2H, CH 2 CH 2 =CH), (m, 2H, CH 2 N), (m, 1H, CHO), 4.63 (br.d, J = 14.0 Hz, 2H, CH 2 =CMe), (m, 2H, CH 2 =CH), 5.57 (br.t, J = 5.3 Hz, 1H, NH), (m, 1H, CH 2 =CH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 4.5 (CH 3 Si), 4.3 (CH 3 Si), 12.1 (CH 3 CH 2 ), 12.1 (CH 3 CH 2 ), 18.0 (CMe 3 ), 22.2 (CH 3 ), 22.5 (CH 2 ), 25.6 (CH 2 ), 25.8 [(CH 3 ) 3 ], 26.0 (CH 2 ), 26.6 (CH 2 ), 28.1 (CH 2 ), 32.3 (CH 2 ), 37.7 (CH 2 CH=CH 2 ), 37.8 (CH 2 CH=CH 2 ), 39.7 (CH 2 NH), 44.7 (CH), 49.7 (CH), 73.5 (CHO), (CH 2 =CH), (CH 2 =CH), (CH 2 =CH), (CH 2 =CMe), (CO); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 26 H 52 NO 2 Si , found O-[(tert-Butyldimethylsilyl)oxy]-6,7-didehydrofluvirucinin B 1 (17): A solution of second-generation Hoveyda-Grubbs catalyst (40 mg, mmol) in anhydrous toluene (32 ml) was added to a solution of 16 (138 mg, 0.32 mmol) and 1,4-benzoquinone (3.5 mg, mmol) in anhydrous toluene (160 ml) at room temperature, and the resulting mixture was heated at 80 ºC for 17 h. The solvent was evaporated, and the resulting residue was chromatographed (from CH 2 Cl 2 to 99:1 CH 2 Cl 2 Et 2 O) to yield lactam 17Z (56 mg, 43%) as a brown foam and its diastereoisomer 17E (45 mg, 35%) as a brown oil. 17Z: IR (film): = 3292, 2959, 1641, 1549, 1462 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.03 [s, 6H, Si(CH 3 ) 2 ], 0.82 (t, J = 7.1 Hz, 3H, CH 3 CH 2 ), S15

16 [m, 12H, CH 3 CH 2, (CH 3 ) 3 ], (m, 12H), 1.68 (s, 3H, CH 3 ), (m, 2H), (m, 2H), 2.20 (m, 2H), 2.98 (dm, J = 6.6 Hz, 1H, H-13), (m, 2H, H-9, H-13), 5.19 (brt, J = 7.0 Hz, 1H, H-7), 5.62 (dd, J = 8.1, 3.7 Hz, 1H, NH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 4.6 (CH 3 Si), 4.2 (CH 3 Si), 10.5 (CH 3 CH 2 ), 12.3 (CH 3 CH 2 ), 18.2 (CMe 3 ), 21.9 (CH 2 ), 24.0 (CH 3 ), 25.7 (CH 2 ), 26.0 [(CH 3 ) 3 ], 26.7 (CH 2 ), 26.9 (CH 2 ), 27.5 (CH 2 ), 32.4 (C-5), 32.8 (C-8), 33.6 (CH 2 ), 39.1 (C-13), 43.9 (C-10), 49.7 (C-2), 74.0 (C-9), (C-7), (C-6), (C-1); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 24 H 48 NO 2 Si , found E: IR (film): = 3292, 2959, 1641, 1549, 1462 cm -1 ; H (400 MHz; CDCl 3 ; Me 4 Si) 0.04 (s, 3H, CH 3 Si), 0.06 (s, 3H, CH 3 Si), [m, 15H, 2CH 3 CH 2, (CH 3 ) 3 ], (m, 1H), (m, 8H), (m, 3H), 1.60 (s, 3H, CH 3 ), (m, 1H), (m, 3H, H-2, H-5), (m, 1H, H-8), (m, 1H, H-8), 3.01 (m, 1H, H-13), (m, 1H, H-13), 3.70 (ddd, J = 7.4, 4.3, 3.2 Hz, 1H, H-9), 5.27 (br.t, J = 7.0 Hz, 1H, H-7), 5.32 (br.s, 1H, NH); C (100.6 MHz; CDCl 3 ; Me 4 Si) 4.8 (CH 3 Si), 4.4 (CH 3 Si), 11.4 (CH 3 CH 2 ), 12.4 (CH 3 CH 2 ), 16.9 (CH 3 ), 18.1 (CMe) 3, 22.1 (CH 2 ), 24.8 (CH 2 ), 25.0 (CH 2 ), 25.9 [(CH 3 ) 3 ], 26.3 (CH 2 ), 27.4 (CH 2 ), 31.3 (CH 2 ), 33.2 (C-8), 37.4 (C-5), 39.7 (C-13), 43.6 (C-10), 48.3 (C-2), 73.3 (C-9), (C-7), (C-6), (C-1); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 24 H 48 NO 2 Si , found O-[(tert-Butyldimethylsilyl)oxy]fluvirucinin B 1 (18): From 17Z: A solution of 17Z (30 mg, mmol) in toluene (3 ml) containing Pd/C (26 mg) was hydrogenated at room temperature and atmospheric pressure for 17 h. The catalyst was removed by filtration over Celite. The organic solution was concentrated, and the resulting oil was chromatographed (from CH 2 Cl 2 to 98:2 CH 2 Cl 2 Et 2 O) and then crystallized (9:1 hexane EtOAc) to give pure 18 (27 mg, 90%) as white solid. From a mixture of diastereoisomers E-Z: Operating as above, from a 1.2:1 mixture of macrocycles 17Z-17E (47 mg, 0.11 mmol) and Pd/C (41 mg) in anhydrous toluene (4.7 ml), compound 18 (43 mg, 91%) was obtained after flash chromatography (from CH 2 Cl 2 to 98:2 CH 2 Cl 2 Et 2 O) and crystallization (9:1 hexane EtOAc): mp ºC [Lit 7 mp ºC]; [ ] 22 D (c 0.02, CH 2 Cl 2 ) {Lit 7 [ ] 22 D (c 0.02, CH 2 Cl 2 )}; IR (film): = 3297, 2928, 1642, 1552 cm -1 ; H (400 MHz; C 6 D 6 ; Me 4 Si) 0.11 (s, 3H, CH 3 Si), 0.12 (s, 3H, CH 3 Si), 0.82 (t, J = 7.4 Hz, 3H, CH 3 CH 2 ), 0.89 (t, J = 7.4 Hz, 3H, CH 3 CH 2 ), 0.97 (d, J = 7.0 Hz, 3H, CH 3 CH), 1.04 [s, (CH 3 ) 3, 9H], (m, 9H), (m, 6H), (m, 4H), (m, 2H), 2.47 (dm, J = 13.7 Hz, 1H, H-13), 3.52 (dt, J = 9.1, 3.4 Hz, 1H, H-9), 3.77 (m, 1H, H-13), 4.53 (dd, J = 9.0, 3.0 Hz, 1H, NH); C (100.6 MHz; C 6 D 6 ; Me 4 Si) 7,8 4.7 (CH 3 Si), 3.7 (CH 3 Si), 9.2 (CH 3 CH 2 ), 12.5 (CH 3 CH 2 ), S16

17 18.4 (CMe 3 ), 20.9 (CH 3 ), 21.1 (CH 2 ), 24.4 (CH 2 ), 25.2 (CH 2 ), 25.9 (CH 2 ), 26.2 [(CH 3 ) 3 ], 26.3 (CH 2 ), 27.0 (CH 2 ), 28.5 (CH 2 ), 31.5 (C-6), 34.1 (CH 2 ), 34.8 (CH 2 ), 38.7 (CH 2 ), 42.9 (C-10), 50.9 (C-2), 73.1 (C-9), (C-1); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 24 H 50 NO 2 Si , found Fluvirucinin B 1 : A solution of 18 (9 mg, mmol) in 1% HCl-EtOH (2 ml) was stirred at room temperature for 2 h. Then, the solution was concentrated to give fluvirucinin B 1 (6 mg, 92%) as a white solid: mp ºC [Lit 9 mp ºC]; [ ] 22 D (c in 1:1 CHCl 3 -CH 3 OH); IR (film): = 3308, 2953, 2926, 2872, 2855, 1635 cm -1 ; H (400 MHz; 1:1 CD 3 OD CDCl 3 ; Me 4 Si) 0.88 (t, J = 7.4 Hz, 3H, CH 3 CH 2 ), 0.89 (t, J = 7.3 Hz, 3H, CH 3 CH 2 ), 0.91 (d, J = 6.9 Hz, 3H, CH 3 ), (m, 3H, CH 2, OH), (m, 11H, 5CH 2, H-10), (m, 7H, 3CH 2, H-6), (m, 1H, H-2), 2.69 (m, 1H), (masked, 1H, H-9), 3.75 (m, 1H), 7.88 (dd, J = 8.5, 4.1 Hz, 1H, NH); C (100.6 MHz; CD 3 OD CDCl 3 ; Me 4 Si) 11.7 (CH 3 CH 2 ), 13.2 (CH 3 CH 2 ), 22.2 (CH 3 ), 22.8 (CH 2 ), 23.8 (CH 2 ), 26.7 (CH 2 ), 26.8 (CH 2 ), 30.1 (CH 2 ), 31.1 (CH 2 ), 31.3 (CH 2 ), 32.9 (C-6), 34.5 (CH 2 ), 35.0 (CH 2 ), 40.4 (CH 2 ), 45.5 (C-10), 49.9 (masked, C-2), 75.0 (C-9), (C-1); HRMS (ESI-TOF) m/z [M + H] + Calcd for C 18 H 36 NO , found REFERENCES 1. Amat, M.; Bosch, J.; Hidalgo, J.; Cantó, M.; Pérez, M.; Llor, N.; Molins, E.; Miravitlles, C.; Orozco, M.; Luque, J. J. Org. Chem. 2000, 65, Guignard, G.; Llor, N.; Urbina, A.; Bosch, J.; Amat, M. Eur. J. Org. Chem. 2016, Amat, M.; Escolano, C.; Llor, N.; Lozano, O.; Gómez-Esqué, A.; Griera, R.; Bosch, J. Arkivoc 2005, ix, Panek, J. S.; Jain, N. F. J. Org. Chem. 2001, 66, Paquette, L. A.; Duan, M.; Konetzki, I.; Kempmann, C. J. Am. Chem. Soc. 2002, 124, White, J. D.; Hanselmann, R.; Jackson, R. W.; Porter, W. J.; Ohba, Y.; Tiller, T.; Wang, S. J. Org. Chem. 2001, 66, Trost, B. M.; Ceschi, M. A.; König, B. Angew. Chem. Int. Ed. 1997, 36, Xu, Z.; Johannes, C. W.; Houri, A. F.; La, D. S.; Cogan, D. A.; Hofilena, G. E.; Hoveyda, A. H. J. Am. Chem. Soc. 1997, 119, Naruse, N.; Tsuno, T.; Sawqada, Y.; Konishi, M.; Oki, T. J. Antibiotics 1991, 44, S17

18 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S18

19 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S19

20 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S20

21 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S21

22 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S22

23 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S23

24 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S24

25 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S25

26 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S26

27 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S27

28 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S28

29 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S29

30 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S30

31 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S31

32 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz, CDCl 3 ; Me 4 Si) S32

33 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S33

34 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S34

35 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S35

36 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S36

37 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) S37

38 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S38

39 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S39

40 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) S40

41 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S41

42 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S42

43 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S43

44 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S44

45 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S45

46 1 H NMR (400 MHz; CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; CDCl 3 ; Me 4 Si) S46

47 1 H NMR (400 MHz; C 6 D 6 ; Me 4 Si) 13 C NMR (100.6 MHz; C 6 D 6 ; Me 4 Si) S47

48 1 H NMR (400 MHz; 1:1 CD 3 OD-CDCl 3 ; Me 4 Si) 13 C NMR (100.6 MHz; 1:1 CD 3 OD-CDCl 3 ; Me 4 Si) S48

49 Table 1. Crystal data and structure refinement for 18. Identification code Jb118 Empirical formula C48 H98 N2 O4 Si2 Formula weight Temperature 293(2) K Wavelength Å Crystal system Monoclinic Space group P 21 Unit cell dimensions a = (2) Å = 90. b = (6) Å = (2). c = (3) Å = 90. Volume (11) Å 3 Z 2 Density (calculated) Mg/m 3 Absorption coefficient mm -1 F(000) 920 Theta range for data collection to Index ranges -10<=h<=11, -25<=k<=25, -16<=l<=13 Reflections collected Independent reflections 9939 [R(int) = ] Completeness to theta = % Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 9939 / 58 / 580 Goodness-of-fit on F Final R indices [I>2sigma(I)] R1 = , wr2 = R indices (all data) R1 = , wr2 = Absolute structure parameter 0.02(4) Largest diff. peak and hole and e.å -3 S49

50 Table 2. Atomic coordinates ( x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for jb118. U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. x y z U(eq) Si(2) -710(2) 5453(1) 2042(2) 70(1) O(1) 3295(4) 3332(3) 7669(5) 82(2) O(9) 4788(5) 2287(3) 2857(3) 79(2) O(21) -1802(4) 3400(3) 7072(3) 64(1) O(29) 83(5) 5023(2) 2942(3) 61(1) N(14) 5517(5) 3044(2) 7622(4) 49(1) N(34) 427(5) 3173(2) 6911(4) 50(1) C(1) 4509(6) 3474(3) 7669(5) 52(2) C(2) 4968(7) 4161(3) 7714(6) 62(2) C(3) 4465(8) 4481(4) 6719(6) 75(2) C(4) 5241(8) 4274(4) 5848(6) 66(2) C(5) 4563(7) 4479(4) 4832(6) 73(2) C(6) 5301(8) 4258(5) 3933(6) 80(2) C(7) 5466(7) 3540(4) 3893(5) 69(2) C(8) 4100(6) 3175(4) 3836(5) 63(2) C(9) 4229(7) 2458(4) 3769(5) 62(2) C(10) 5117(7) 2138(3) 4645(5) 56(2) C(11) 4679(6) 2344(3) 5657(4) 51(1) C(12) 5599(7) 2088(3) 6558(5) 56(2) C(13) 5255(8) 2367(3) 7546(5) 58(2) Si(1)* 3750(8) 2341(5) 1733(4) 64(2) C(15)* 3280(30) 3133(12) 1189(15) 96(8) C(16)* 2060(20) 1912(14) 1869(16) 104(8) C(17)* 4870(30) 1941(11) 901(15) 94(12) C(18)* 4050(30) 1752(17) -99(17) 127(11) C(19)* 5450(40) 1343(12) 1410(20) 138(12) Si(1A)** 4061(4) 1944(4) 1821(3) 72(2) C(15A)** 2840(20) 2551(13) 1229(16) 143(9) C(16A)** 3090(20) 1190(10) 2032(13) 127(8) C(17A)** 5450(20) 1774(7) 1023(11) 65(4) C(18A)** 4870(20) 1392(8) 94(10) 84(5) C(19A)** 6620(20) 1418(9) 1615(12) 102(6) C(20) 6068(12) 2366(5) 644(8) 111(4) C(21)* -585(5) 3455(3) 7367(4) 46(1) S50

51 C(21A)** 4421(10) 4483(4) 8621(7) 87(3) C(22)* -104(6) 3859(3) 8279(5) 52(1) C(22A)** 4954(11) 4213(6) 9615(7) 113(4) C(23) -432(8) 4552(3) 8037(5) 60(2) C(24) 426(7) 4824(3) 7252(5) 57(2) C(25) 44(7) 5476(3) 6872(5) 60(2) C(26) 926(7) 5719(3) 6054(5) 59(2) C(27) 882(7) 5269(3) 5145(5) 55(2) C(28) -555(6) 5101(3) 4646(5) 54(2) C(29) -539(7) 4684(3) 3712(5) 54(2) C(30) 221(6) 4053(3) 3894(5) 50(1) C(31) -307(6) 3673(3) 4748(5) 52(1) C(32) 567(7) 3101(3) 5070(5) 57(2) C(33) 165(7) 2783(3) 6018(5) 57(2) C(35) -1664(16) 6134(6) 2550(8) 144(5) C(36) -1990(9) 4971(5) 1246(7) 96(3) C(37) 742(11) 5720(5) 1309(7) 96(3) C(38) 1496(11) 5139(6) 938(8) 109(4) C(39) 1725(15) 6130(6) 1988(10) 152(6) C(40) 131(13) 6110(6) 383(7) 117(4) C(61) 4586(11) 4529(6) 2957(8) 118(4) C(101) 5131(8) 1418(4) 4526(6) 74(2) C(102) 3758(9) 1095(4) 4678(9) 99(3) C(221) -801(8) 3614(4) 9180(5) 70(2) C(222) -486(11) 2930(5) 9430(7) 91(3) C(261) 527(10) 6387(4) 5738(7) 79(2) C(301) 233(7) 3661(4) 2926(5) 60(2) C(302) -1135(8) 3362(4) 2531(6) 79(2) Partial occupation factors of 0.415(12)* and 0.585(12)** S51

52 Table 3. Bond lengths [Å] and angles [ ] for jb118. Si(2)-O(29) 1.636(5) Si(2)-C(36) 1.852(9) Si(2)-C(35) 1.875(11) Si(2)-C(37) 1.878(11) O(1)-C(1) 1.211(7) O(9)-C(9) 1.430(8) O(9)-Si(1A) 1.657(7) O(9)-Si(1) 1.726(9) O(21)-C(21) 1.208(7) O(29)-C(29) 1.435(8) N(14)-C(1) 1.339(8) N(14)-C(13) 1.456(8) N(34)-C(21) 1.343(7) N(34)-C(33) 1.453(8) C(1)-C(2) 1.516(10) C(2)-C(3) 1.528(11) C(2)-C(21A) 1.533(11) C(3)-C(4) 1.514(11) C(4)-C(5) 1.512(11) C(5)-C(6) 1.531(12) C(6)-C(61) 1.526(12) C(6)-C(7) 1.528(13) C(7)-C(8) 1.524(9) C(8)-C(9) 1.524(11) C(9)-C(10) 1.537(9) C(10)-C(11) 1.523(8) C(10)-C(101) 1.530(11) C(11)-C(12) 1.523(8) C(12)-C(13) 1.514(9) Si(1)-C(17) 1.84(2) Si(1)-C(15) 1.86(2) Si(1)-C(16) 1.894(17) C(17)-C(19) 1.52(3) C(17)-C(20) 1.53(2) C(17)-C(18) 1.54(2) Si(1A)-C(17A) 1.835(17) Si(1A)-C(15A) 1.86(2) S52