1. General information 1 H NMR spectra were recorded at 400 MHz with JEOL ECS-400 instruments. Coupling constants (J) are reported in Hz. 13 C NMR spe

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1 Stereoselective Synthesis of Tabtoxinine-β-lactam by using the Vinylogous Mukaiyama Aldol Reaction with Acetate-type Vinylketene Silyl N,O-Acetal and α-keto-β-lactam Hirotaka Ejima, Fumihiro Wakita, Ryo Imamura, Takuya Kato, and Seijiro Hosokawa* Department of Applied Chemistry, Faculty of Science and Engineering, Waseda University Ohkubo, Shunjuku-ku, Tokyo , Japan Supporting Information Table of Contents 1. General information 2. Experimental details 3. References 4. 1 H NMR and 13 C NMR spectra of new compounds S2 S3-S16 S17 S18-S48 S1

2 1. General information 1 H NMR spectra were recorded at 400 MHz with JEOL ECS-400 instruments. Coupling constants (J) are reported in Hz. 13 C NMR spectra were recorded at 100 MHz with JEOL ECS-400 instruments. Chemical shifts (δ) are quoted in parts per million (ppm) and referenced to the residual solvent peak (CDCl ppm for 1 H, ppm for 13 C; C 6 D ppm for 1 H, D 2 O 4.72 ppm for 1 H, ppm (MeOH as internal standard) for 13 C). The following abbreviations were used for multiplicities (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet). Melting point (mp) determinations were performed by using a Yanako MP-S3 instrument. FT-IR spectra were recorded with ThermoFisher SCIENTIFIC NICOLET 6700 FT-IR. HR-MS and MS were obtained with a ThermoFisher EXACTIVE PLUS and JEOL JMS-GCMATEII, respectively. Optical rotations were measured with a JASCO P X-ray crystallographic analysis was performed with Rigaku RAXIS-RAPID. All reactions were monitored by TLC (silica gel 60 F 254, Merck). THF was distilled from Na before use. CH 2 Cl 2 was distilled from P 2 O 5 immediately before use. Molecular sieves 4A was activated by heating at 250 C in vacuo before use. All moisture sensitive reactions were performed under a static argon atmosphere in glassware with magnetic stirring. S2

3 2. Experimental details -Keto- -lactam 6 was prepared from S1 according to the Paquette s procedure. S1 Synthesis of compound S2 To a solution of methyl 3-hydroxy-2-methylene butyrate S1 (9.38 ml, 77.3 mmol) in MeOH (100 ml) was added p-methoxybenzylamine (10.0 ml, 77.3 mmol). After stirring for 2 d at room temperature, the resulting mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 1:4) to give compound S2 as a colorless oil (16.1 g, 60.3 mmol, 78%). R f value: 0.27 (n-hexane/ethyl acetate = 1:4); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (2H, m), (2H, m), 4.19 (1H, dq, J = 6.8, 6.5 Hz), 3.77 (3H, s), 3.70 (2H, s), 3.68 (3H, s), 3.07 (1H, dd, J = 12.2, 7.0 Hz), 2.98 (1H, dd, J = 12.2, 4.0 Hz), 2.45 (1H, ddd, J = 7.0, 6.8, 4.0 Hz), 1.16 (3H, d, J = 6.5 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 173.5, 158.8, 131.0, 129.4, 113.8, 70.1, 55.2, 53.1, 51.7, 50.8, 48.4, 21.8; HRMS (ESI) m/z calcd for C 14 H 22 O 4 N [M+H] +, ; found ; IR (thin film, KBr) 3317, 2952, 2837, 1731, 1513, 1247, 1174, 1034, 818 cm -1. S3

4 Synthesis of compound S3 To a solution of compound S2 (6.77 g, 25.3 mmol) in THF (33.9 ml) was added t-bumgcl solution (101 ml, 101 mmol, 1.0 M in THF) at 0 C and warmed to room temperature. After stirring for 3 h, saturated aqueous solution of NH 4 Cl (67.7 ml) was added at 0 C. The resulting mixture was filtered through a pad of celite and concentrated under reduced pressure to a volume of 70 ml. Ethyl acetate (100 ml) was added to the mixture and phases were separated. The aqueous layer was extracted with ethyl acetate (100 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/acetone = 3:2) to give the compound S3 as a white solid (5.73 g, 24.4 mmol, 96%). R f value: 0.28 (n-hexane/acetone = 3:2); mp C; 1 H NMR (C 6 D 6, 400 MHz): δ (ppm) (2H, m), (2H, m), 4.16 (1H, d, J = 15.0 Hz), 3.95 (1H, d, J = 15.0 Hz), 3.82 (1H, qd, J = 6.5, 5.5 Hz), 3.27 (3H, s), 2.80 (1H, dd, J = 5.5, 2.5 Hz), 2.76 (1H, ddd, J = 5.5, 5.5, 2.5 Hz), 2.58 (1H, dd, J = 5.5, 5.5 Hz), (1H, brs), 1.01 (3H, d, J = 6.5 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 168.2, 159.1, 129.4, 127.5, 114.1, 65.0, 56.8, 55.2, 45.3, 40.9, 21.3; HRMS (ESI) m/z calcd for C 13 H 17 O 3 NNa [M+Na] +, ; found ; IR (thin film, KBr) 3406, 2966, 1727, 1514, 1247 cm -1. Synthesis of compound S4 To a solution of compound S3 (7.21 g, 30.6 mmol) in dichlorormethane (72.1 ml) was added triethylamine (6.42 ml, 46.0 mmol) and methanesulfonyl chloride (2.84 ml, 36.7 mmol) at 0 C. S4

5 After stirring for 5 min, the resulting mixture was diluted with water (70.0 ml) and layers were separated. The aqueous layer was extracted with dichloromethane (70.0 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flush column chromatography on silica gel (ethyl acetate) to give the mesylated compound, which was immediately used to the next reaction. To a solution of the resulting mesylated compound in toluene (72.1 ml) was added DBU (4.86 ml, 32.2 mmol) and warmed to 70 C. After stirring for 2 h, the reaction mixture cooled to room temperature, and acidified to ph 2 with 1 M HCl. The layers were separated and the aqueous layer was extracted with toluene (70.0 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flush column chromatography on silica gel (n-hexane/ethyl acetate = 3:2) to give E/Z mixture of compound S4 (E/Z 5:1) as a pale yellow solid (5.79 g, 26.7 mmol, 87% in 2 steps). [(E)-isomer]: white solid; R f value: 0.38 (n-hexane/ethyl acetate = 1:1); mp C; 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (2H, m), (2H, m), 6.16 (1H, qt, J = 7.0, 1.5 Hz), 4.43 (2H, s), 3.80 (3H, s), 3.60 (2H, d. J = 1.5 Hz), 1.70 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 163.8, 159.1, 138.1, 129.4, 127.7, 121.3, 114.1, 55.3, 46.3, 45.3, 14.2; HRMS (ESI) m/z calcd for C 13 H 15 O 2 NNa [M+Na] +, ; found ; IR (thin film, KBr) 2944, 1744, 1513, 1386, 1246, 1032, 772 cm -1. [(Z)-isomer]: pale yellow oil; R f value: 0.55 (n-hexane/ethyl acetate = 1:1); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (2H, m), (2H, m), 5.59 (1H, qt, J = 7.0, 1.0 Hz), 4.42 (2H, s), 3.80 (3H, s), 3.51 (2H, d. J = 1.0 Hz), 2.04 (3H, d, J = 7.0 Hz) ; 13 C NMR (CDCl 3, 400MHz): δ (ppm) 164.3, 159.0, 136.7, 129.4, 127.8, 124.8, 114.0, 55.2, 46.9, 45.1, 14.6; HRMS (ESI) m/z calcd for C 13 H 15 O 2 NNa [M+Na] +, ; found ; IR (thin film, KBr) 2942, 1733, 1513, 1390, 1246, 1033, 795 cm -1. Synthesis of compound 6 To a solution of compound S4 (5.92 g, 27.3 mmol) in 1,4-dioxane (118 ml) and water (39.4 ml) were added 2,6-lutidine (6.31 ml, 54.5 mmol), 4% osmium tetroxide in water (3.46 ml, mmol) and sodium periodate (23.3 g, 109 mmol) at 0 C. After strirring 2.5 h at room temperature, S5

6 the resulting mixture was diluted with water (195 ml) and dichloromethane (390 ml). Layers were separated and the aqueous layer was extracted with dichloromethane (390 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 2:3) to give compound 6 as a pale yellow solid (4.32 g, 22.6 mmol, 83%). R f value: 0.27 (n-hexane/ethyl acetate = 2:3); mp C; 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (2H, m), (2H, m), 4.70 (2H, s), 3.81 (3H, s), 3.76 (2H, s); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 192.9, 163.3, 159.7, 129.8, 125.4, 114.5, 58.8, 55.3, 46.4; HRMS (ESI) m/z calcd for C 11 H 11 O 3 NNa [M+Na] +, ; found ; IR (thin film, KBr) 1821, 1764, 1514, 1247, 1219, 772 cm -1. S6

7 Synthesis of compound 12 A solution of compound 6 in dichloromethane (5.0 w/v%) was dried over molecular sieves 4A (500 wt%)for 4 h at room temperature. The supernatant solution was transferred by syringe to another flask and concentrated under reduced pressure. To a solution of compound 6 (25.5 mg, mmol) and compound 3 (87.7mg, mmol) in dichloromethane (1.02 ml) was added tin(iv) chloride (43.6 μl, mmol) at -78 C. After stirring for 12 h, pyridine (120 μl, 1.49 mmol) was added to the reaction mixture and the resulting mixture was warmed to room temperature. Then, a mixture of sat. NaHCO 3 aq. and sat. Rochelle salt aq. (1:1, 2.04 ml) was added to the solution. The resulting two-phase mixture was stirred vigorously for 1 h. After the layers were separated, the aqueous layer was extracted with dichloromethane (1.2 ml 3). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 1:1) to give compound 12 as colorless oil (66.8 mg, 97%). R f value: 0.20 (n-hexane / ethyl acetate = 1:1); Optical rotation: [α] 24 D (c 1.02, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (2H, m), (9H, m), (2H, m), 7.07 (1H, ddd, J = 15.5, 7.0, 7.0 Hz), (2H, m), 5.45 (1H, d, J = 3.0 Hz), 4.33 (1H, d, J = 15.0 Hz), 4.26 (1H, d, J = 15.0 Hz), 3.80 (3H, s), 3.18 (1H, s), 3.18 (1H, d, J = 6.0 Hz), 3.16 (1H, J = 6.0 Hz), 2.78 (1H, ddd, J = 15.5, 7.0, 1.0 Hz), 2.67 (1H, ddd, J = 15.5, 7.0, 1.0 Hz), 1.98 (1H, qqd, J = 7.0, 7.0, 3.0 Hz), 0.89 (3H, d, J = 7.0 Hz), 0.76 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 169.7, 164.2, 159.2, 152.9, 143.6, 142.2, 138.2, 129.5, 128.9, 128.6, 128.3, 127.9, 126.7, 125.9, 125.6, 124.0, 114.3, 89.4, 83.1, 64.3, 55.3, 53.3, 45.0, 37.8, 30.1, 21.8, 16.3; HRMS (ESI) m/z calcd for C 33 H 34 O 6 N 2 Na [M+Na] +, ; found ; IR (thin film, KBr) 3355, 2965, 1778, 1734, 1514, 1351, 1247, 1176, 760 cm -1. S7

8 Synthesis of compound 15 To a solution of 12 (2.35g, 4.23 mmol) in ethyl acetate (71.0 ml) was added 10% Pd/C (235 mg, mmol) and stirred for 2 h at room temperature. The mixture was filtered through a pad of celite. The filtrate was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 2:3) to give the compound 15 as white solid (2.36 g, 4.23 mmol, quant.). R f value: 0.40 (n-hexane/ethyl acetate = 2:3); mp C; Optical rotation: [α] 23 D (c 1.03, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (2H, m), (8H, m), (2H, m), (2H, m), 5.36 (1H, d, J = 3.0 Hz), 4.31 (2H, s), 3.80 (3H, s), (1H, m), 3.11 (2H, s), (1H, m), (1H, m), 1.96 (1H, qqd, J = 7.0, 7.0, 3.0 Hz), (4H, m), 0.86 (3H, d, J = 7.0 Hz), 0.74 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 172.7, 170.3, 159.2, 153.0, 142.2, 138.0, 129.5, 128.9, 128.6, 128.4, 127.9, 127.0, 125.9, 125.6, 114.2, 89.5, 84.4, 64.4, 55.3, 53.8, 44.9, 34.9, 33.6, 29.8, 21.8, 18.6, 16.4; HRMS (ESI) m/z calcd for C 33 H 36 O 6 N 2 Na [M+Na] +, ; found ; IR (thin film, KBr) 3368, 2964, 1782, 1732, 1514, 1247, 1176, 759 cm -1. The absolute configuration of 15 was determined by X-ray crystallography. Fig. S1. ORTEP drawing of 15 S8

9 Synthesis of compound 16 PMBN OH O O N Ph O O Ph BOMCl TBAI i-pr 2 NEt THF 65 C, 12 h quant. BOMO PMBN O O Ph Ph N O O To a solution of compound 15 (1.98 g, 3.56 mmol) and tetrabutylammonium iodide (1.31 g, 3.56 mmol) in THF (19.8 ml) were added N,N-diisopropylethylamine (1.81 ml, 10.7 mmol) and benzyl chloromethyl ether (1.47 ml, 10.7 mmol). After strirring for 12 h at 65 C, the resulting mixture was added sat. NaHCO 3 aq. (19.8 ml) at 0 C and concentrated under reduced pressure to a volume of 20 ml. Chloroform (20 ml) was added to the mixture and phases were separated. The aqueous layer was extracted with chloroform (20 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/acetone = 4:1) to give the compound 16 as a colorless oil (2.41 g, 3.56 mmol, quant.). R f value: 0.30 (n-hexane/acetone = 3:1); Optical rotation: [α] 23 D 97.2 (c 1.00, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (2H, m), (13H, m), (2H, m), (2H, m), 5.36 (1H, d, J = 3.0 Hz), 4.98 (1H, d, J = 7.0 Hz), 4.90 (1H, d, J = 7.0 Hz), 4.64 (1H, d, J = 12.0 Hz), 4.58 (1H, d, J = 12.0 Hz), 4.36 (1H, d, J = 15.0 Hz), 4.27 (1H, d, J = 15.0 Hz), 3.78 (3H, s), 3.45 (1H, d, J = 6.0 Hz), 2.99 (1H, d, J = 6.0 Hz), 2.96 (1H, ddd, J = 17.0, 6.5, 6.5 Hz), 2.75 (1H, d, J = 17.0, 7.5, 6.0 Hz), 1.96 (1H, qqd, J = 7.0, 7.0, 3.0 Hz), (4H, m), 0.86 (3H, d, J = 7.0 Hz), 0.74 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 172.4, 168.5, 159.1, 153.0, 142.2, 138.1, 137.5, 129.4, 128.9, 128.6, 128.3, 128.3, 127.9, 127.8, 127.6, 127.1, 125.9, 125.5, 114.1, 91.7, 89.3, 88.9, 70.0, 64.3, 55.2, 51.0, 44.9, 35.0, 33.4, 29.8, 21.8, 18.7, 16.4; HRMS (ESI) m/z calcd for C 41 H 44 O 7 N 2 Na [M+Na] +, ; found ; IR (thin film, KBr) 2963, 1782, 1751, 1704, 1514, 1247, 1176, 1035, 751, 699 cm -1. S9

10 Synthesis of compound 17 To a mixture of KHMDS solution (10.1 ml, 5.07 mmol, 0.5 M in toluene) and THF (26.4 ml) was added via cannula a precooled solution of compound 16 (2.64 g, 3.90 mmol) in THF (20.0 ml) at -78 C. Residual 16 was rinsed in with two 3.2 ml of THF, and stirring was continued at -78 C for 30 min. A precooled solution of trisyl azide S2 (1.57g, 5.07 mmol) in THF (26.4 ml) was added via cannula to the solution of potassium enolate at -78 C. After 20 min, the reaction was quenched with glacial acetic acid (1.03 ml, 17.9 mmol). The reaction mixture was immediately warmed to 30 C and stirred for 1 h. Dichloromethane (100 ml) and dilute brine (100 ml) was added to the mixture and layers were separated. The aqueous layer was extracted with dichloromethane (100 ml 2). The combined organic layer was washed with sat. NaHCO 3 aq (100 ml 3) and dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (toluene/ethyl acetate = 12:1) to give the compound 17 as a colorless oil (2.22 g, 3.09 mmol, 82%). The diastereomer of 17 can be separated by column chromatography on silica gel (n-hexane/acetone = 3:1). R f value: 0.27 (toluene/ethyl acetate = 12:1); Optical rotation: [α] 23 D 82.0 (c 1.08, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (2H, m), (13H, m), (2H, m), (2H, m), 5.35 (1H, d, J = 3.5 Hz), 5.02, (1H, dd, J = 8.0, 4.0 Hz), 4.90 (1H, d, J = 7.0 Hz), 4.80 (1H, d, J = 7.0 Hz), 4.57 (1H, d, J = 12.0 Hz), 4.53 (1H, d, J = 12.0 Hz), 4.37 (1H, d, J = 15.0 Hz), 4.21 (1H, d, J = 15.0 Hz), 3.78 (3H, s), 3.40 (1H, d, J = 6.0 Hz), 2.80 (1H, d, J = 6.0 Hz), 2.02 (1H, qqd, J = 7.0, 7.0, 3.5 Hz), (4H, m), 0.90 (3H, d, J = 7.0 Hz), 0.80 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 169.9, 168.1, 159.2, 152.4, 141.9, 137.5, 137.4, 129.4, 129.0, 128.7, 128.5, 128.4, 128.1, 127.9, 127.7, 127.0, 125.7, 125.4, 114.2, 91.7, 90.0, 88.2, 70.1, 65.1, 59.8, 55.2, 50.8, 44.9, 30.6, 29.7, 25.3, 21.6, 16.2; HRMS (ESI) m/z calcd for C 41 H 43 O 7 N 5 Na [M+Na] +, ; found ; IR (thin film, KBr) 2965, 2105, 1783, 1751, 1708, 1514, 1248, 1209, 1177, 1035, 760, 699 cm -1. S10

11 Synthesis of compound 18 To a solution of compound 17 (669 mg, mmol) in MeCN (13.7 ml) was added celium (IV) ammonium nitrate (1.12 g, 2.05 mmol) at room temperature. After stirring for 30 min, H 2 O (4.55 ml) was added dropwise and stirred for 12 h. Na 2 S 2 O 3 (324 mg, 2.05 mmol) and sat. NaHCO 3 aq. (20 ml) were added to the resulting mixture at 0 C. Ethyl acetate (20 ml) was added to the mixture and layers were separated. The aqueous layer was extracted with ethyl acetate (20 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 2:1) to give the compound 18 as a colorless oil (394 mg, mmol, 71%). R f value: 0.23 (n-hexane/ethyl acetate = 2:1); Optical rotation: [α] 23 D 87.6 (c 2.54, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (2H, m), (13H, m), 5.57 (1H, s), 5.37 (1H, d, J = 3.5 Hz), 5.04 (1H, dd, J = 8.0, 4.5 Hz), 4.90 (1H, d, J = 7.0 Hz), 4.85 (1H, d, J = 7.0 Hz), 4.59 (2H, s), 3.58 (1H, d, J = 6.0 Hz), 2.93 (1H, d, J = 6.0 Hz), 2.02 (1H, qqd, J = 7.0, 7.0, 3.5 Hz), (4H, m), 0.91 (3H, d, J = 7.0 Hz), 0.81 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 169.9, 169.2, 152.5, 142.0, 137.5, 137.3, 129.0, 128.7, 128.5, 128.4, 128.2, 128.0, 127.8, 125.7, 125.4, 91.6, 90.0, 89.9, 70.2, 65.1, 59.8, 47.5, 30.7, 29.7, 25.3, 21.6, 16.3; HRMS (ESI) m/z calcd for C 33 H 35 O 6 N 5 Na [M+Na] +, ; found ; IR (thin film, KBr) 3306, 2966, 2104, 1779, 1709, 1368, 1211, 1178, 1051, 761, 699 cm -1. S11

12 Synthesis of compound 19 A mixture of titanium tetraisopropoxide (365 μl, 1.23 mmol) and benzyl alcohol (2.56 ml) was stirred under the vacuum (10 mmhg) for 30 min in order to remove the 2-propanol and then transferred via cannula to the compound 18 (364 mg, mmol) in a dried flask. The mixture was heated to 80 C for 12 h and was subsequently quenched by the addition of 1 M HCl aq. (10 ml). The solution was extracted with ethyl acetate (10 ml 3). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform/ethyl acetate = 10:1) to give the compound 19 as a colorless oil (229 mg, mmol, 88%). R f value: 0.27 (chloroform/ethyl acetate = 10:1); Optical rotation: [α] 24 D 24.8 (c 2.08, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (10H, m), 5.68 (1H, s), 5.23 (2H, s), 4.98 (1H, d, J = 7.0 Hz), 4.95 (1H, d, J = 7.0 Hz), 4.67 (1H, d, J = 12.0 Hz), 4.63 (1H, d, J = 12.0 Hz), 4.04 (1H, dd, J = 7.5, 4.5 Hz), 3.70 (1H, d, J = 6.0 Hz), 3.16 (1H, d, J = 6.0 Hz), (1H, m), (2H, m), (1H, m); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 170.1, 169.3, 137.2, 135.0, 128.7, 128.6, 128.5, 128.5, , , 91.8, 90.1, 70.4, 67.5, 61.8, 48.0, 31.0, 25.8; HRMS (ESI) m/z calcd for C 22 H 24 O 5 N 4 Na [M+Na] +, ; found ; IR (thin film, KBr) 3284, 2900, 2106, 1759, 1188, 1044, 1027, 739, 698 cm -1. S12

13 The absolute configuration of the C2 position was determined by derivatization to (S)- and (R)- MTPA amides. S3 Synthesis of compound S5 To a solution of compound 19 (11.7 mg, mmol) in THF (292 μl) and H 2 O (59 μl) was added triphenylphosphine (9.7 mg, mmol). After stirring for 12 h at room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform/methanol = 15:1) to give the compound S5 as a white solid (9.0 mg, mmol, 80%). R f value: 0.23 (chloroform/methanol = 15:1); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (10H, m), 5.65 (1H, s), 5.16 (2H, s), 4.98 (1H, d, J = 7.0 Hz), 4.94 (1H, d, J = 7.0 Hz), 4.67 (1H, d, J = 11.5 Hz), 4.63 (1H, d, J =11.5 Hz), 3.67 (1H, d, J = 6.0 Hz), 3.54 (1H, dd, J = 8.0, 5.0 Hz), 3.15 (1H, d, J = 6.0 Hz), (1H, m), (2H, m), (1H, m); HRMS (ESI) m/z calcd for C 22 H 27 O 5 N 2 [M+H] +, ; found Synthesis of compound (S)-MTPA amide S6 To a solution of compound S5 (4.3 mg, mmol) in pyridine (215 μl) was added (R)-MTPACl (3.3 μl, mmol). After stirring for 2 h at room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 1:1) to give the compound S6 as a colorless oil (6.3 mg, mmol, 95%). R f value: 0.33 (n-hexane/ethyl acetate = 1:1); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) (2H, m), (14H, m), 5.63 (1H, s), 5.24 (1H, d, J = 12.0 Hz), 5.14 (1H, d, J = 12.0 S13

14 Hz), 4.88 (1H, d, J = 7.5 Hz), 4.81 (1H, d, J = 7.5 Hz), 4.71 (1H, ddd, J = 7.5, 7.5, 5.5 Hz), 4.59 (1H, d, J = 11.5 Hz), 4.54 (1H, d, J = 11.5 Hz), 3.55 (1H, d, J = 6.0 Hz), 3.48 (3H, s), 2.93 (1H, d, J = 6.0 Hz), (1H, m), (2H, m), (1H, m); HRMS (ESI) m/z calcd for C 32 H 33 O 7 N 2 F 3 Na [M+Na] +, ; found Synthesis of compound (R)-MTPA amide S7 To a solution of compound S5 (4.2 mg, mmol) in pyridine (210 μl) was added (S)-MTPACl (3.2 μl, mmol). After stirring for 12 h at room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 1:1) to give the compound S7 as a colorless oil (5.6 mg, mmol, 86%). R f value: 0.33 (n-hexane/ethyl acetate = 1:1); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.56 (1H, d, J = 7.5 Hz), (2H, m), (13H, m), 5.66 (1H, s), 5.22 (1H, d, J = 12.0 Hz), 5.15 (1H, d, J = 12.0 Hz), 4.98 (1H, d, J = 7.5 Hz), 4.92 (1H, d, J = 7.5 Hz), 4.69 (1H, ddd, J = 7.5, 7.5, 5.5 Hz), 4.67 (1H, d, J = 11.5 Hz), 4.63 (1H, d, J = 11.5 Hz), 3.67 (1H, d, J = 6.0 Hz), 3.33 (3H, s), 3.09 (1H, d, J = 6.0 Hz), (1H, m), (3H, m) ; HRMS (ESI) m/z calcd for C 32 H 33 O 7 N 2 F 3 Na [M+Na] +, ; found Ph O HN O O = S R NHMTPA H 0.02 O O Fig. S2. Δδ values (ppm) obtained for (R) and (S)-MTPA amides Ph S14

15 Synthesis of tabtoxinine-β-lactam (2) To a solution of compound 19 (6.4 mg, mmol) in methanol (256 μl) was added 10% Pd/C (19.2 mg, mmol) and benzylaminehydrochloride (10.8 mg, mmol). After stirring for 12 h at room temperature, the mixture was filtered through a pad of celite. The filtrate was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform/methanol/water = 4:4:1) to give the mixture of tabtoxinine-β-lactam (2) and N-methyltabtoxinine-β-lactam (20) (2/20 =95:5) as white solid (2.4 mg, mmol, 85%). The mixture of 2 and 20 was separated by HPLC (COSMOSIL HILIC Packed Column 4.6mmI.D. 150 mm, MeCN/H 2 O = 4:1, flow rate = 1.0 ml/min, UV = 210 nm, retention time = 20: 8.33 min, 2: min) [tabtoxinine-β-lactam (2)]: R f value: 0.27 (chloroform/methanol/water = 4:4:1); mp C (decomposition); Optical rotation: [α] 24 D 27.1 (c 0.34, H 2 O); 1 H NMR (D 2 O, 400 MHz): δ (ppm) 3.67 (1H, t, J = 5.5 Hz), 3.36 (1H, d, J = 6.5 Hz), 3.24 (1H, d, J = 6.5 Hz), (4H, m); 13 C NMR (D 2 O, 100 MHz, MeOH standard): δ (ppm) 174.8, 174.2, 84.6, 55.1, 51.5, 29.9, 25.5; HRMS (ESI) m/z calcd for C 7 H 12 O 4 N 2 Na [M+Na] +, ; found ; IR (thin film, KBr) 3120, 1735, 1617, 1406, 1205 cm -1. [N-methyltabtoxinine-β-lactam (20)]: R f value: 0.27 (chloroform/methanol/water = 4:4:1); 1 H NMR (D 2 O, 400 MHz): δ (ppm) 3.55 (1H, dd, J = 6.0, 5.0 Hz), 3.35 (1H, d, J = 6.5 Hz), 3.23 (1H, d, J = 6.5 Hz), 2.60 (3H, s), (4H, m); 13 C NMR (D 2 O, 100 MHz, MeOH standard): δ (ppm) 174.1, 173.3, 84.5, 63.2, 51.6, 32.3, 29.6, 24.2; HRMS (ESI) m/z calcd for C 8 H 14 O 4 N 2 Na [M+Na] +, ; found S15

16 [N,N-dimethyltabtoxinine-β-lactam (21)]: R f value: 0.27 (chloroform/methanol /water = 4:4:1); 1 H NMR (D 2 O, 400 MHz): δ (ppm) 3.54 (1H, t, J = 6.0 Hz), 3.36 (1H, d, J = 6.5 Hz), 3.24 (1H, d, J = 6.5 Hz), 2.81 (3H, s), 2.78 (3H, s), (2H, m), (2H, m); 13 C NMR (D 2 O, 100 MHz, MeOH standard): δ (ppm) 174.1, 172.9, 84.5, 70.8, 51.7, 43.8, 40.4, ; HRMS (ESI) m/z calcd for C 9 H 16 O 4 N 2 Na [M+Na] +, ; found HPLC trace COSMOSIL HILIC Packed Column 4.6mmI.D. 150 mm, MeCN/H 2 O = 4:1, flow rate = 1.0 ml/min, UV = 210 nm, retention time = 21: 7.44 min, 20: 8.33 min, 2: min 140 mv Time(min) peak# Ret. Time Area Height Area % Height % S16

17 References (S1) (a) Behrens, C.; Paquette, L. A. Org. Synth., 1998, 75, 106. (b) Paquette, L. A.; Brand, S.; Behrens, C. J. Org. Chem. 1999, 64, (S2) Harmon, R. E; Wellman, G.; Gupta, S. K. J. Org. Chem., 1973, 38, 11. (S3) (a) Kusumi, T.; Fukushima, T.; Ohtani, I; Kakisawa, H. Tetrahedron Lett. 1991, 32, (b) Seco, J. M.; Quiñoá, E.; Riguera, R. Chem. Rev. 2004, 104, 17. S17

18 9HE_1150_michaeladdition_TM2_P_CDCl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1150_michaeladdit Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 2 OCT :37:36 Revision_time = 2 OCT :44:44 Current_time = 2 OCT :45:11 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 26 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 21.7[dC] S X : parts per Million : 1H

19 9HE_1150_michaeladdition_TM2_13C_CDCl3_ jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 21.7[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1150_michaeladdit Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 2 OCT :29:54 Revision_time = 2 OCT :30:00 Current_time = 2 OCT :31:26 Comment = single pulse decouple Dim_size = Dim_title = 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 1000 S X : parts per Million : 13C : parts per Million

20 9HE_1152_lactamization_TM2_P_C6D6_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1152_lactamizatio Experiment = single_pulse.ex2 Solvent = BENZENE D6 Creation_time = 6 DEC :23:16 Revision_time = 6 DEC :26:31 Current_time = 6 DEC :27:06 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 48 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 20.2[dC] S X : parts per Million : 1H

21 9HE_1152_lactamization_TM_13 C_CDCl3_ jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 21.7[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1152_lactamizatio Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 2 OCT :51:40 Revision_time = 2 OCT :51:18 Current_time = 2 OCT :51:58 Comment = single pulse decouple Dim_size = Dim_title = 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 1000 S X : parts per Million : 13C : parts per Million

22 9HE_xx_E1cb(datedori)_P_CDCl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_xx_E1cb(datedori) Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 5 OCT :24:29 Revision_time = 5 OCT :25:08 Current_time = 5 OCT :25: Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 21.1[dC] S X : parts per Million : 1H

23 9HE_xx_E1cb(datedori)_13C_CDCl3_ jdf Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 21.6[dC] Filename = 9HE_xx_E1cb(datedori) Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 5 OCT :07:24 Revision_time = 5 OCT :07:02 Current_time = 5 OCT :07:35 Comment = single pulse decouple Dim_size = Dim_title = 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 500 Total_scans = 500 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ S X : parts per Million : 13C : parts per Million

24 9HE_xx_E1cb_Z product_p_cdcl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_xx_E1cb_Z product Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 12 FEB :39:05 Revision_time = 13 MAR :49:51 Current_time = 13 MAR :50:32 Comment = single_pulse Dim_size = Dim_title = 1H 0.96 X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 36 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 18.9[dC] S X : parts per Million : 1H

25 9HE_xx_E1cb_Z product_13c_cdcl3_ jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 19.2[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_xx_E1cb_Z product Experiment = single_pulse_dec Sample_id = S# Solvent = CHLOROFORM D Creation_time = 12 FEB :32:10 Revision_time = 12 FEB :44:01 Current_time = 12 FEB :45:16 Comment = single pulse decouple Dim_size = Dim_title = 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 1000 S X : parts per Million : 13C : parts per Million

26 9HE_ensyu_sample_P_CDCl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_ensyu_sample_P_CD Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 15 JAN :25:46 Revision_time = 5 OCT :17:24 Current_time = 5 OCT :18:05 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Clipped = TRUE Scans = 16 Total_scans = 16 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 23.1[dC] S X : parts per Million : 1H

27 9HE_ensyu_sample_13C_CDCl3_ jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 23.4[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_ensyu_sample_13C_ Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 15 JAN :54:19 Revision_time = 5 OCT :22:01 Current_time = 5 OCT :22:43 Comment = single pulse decouple Dim_size = Dim_title = 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 1000 S X : parts per Million : 13C : parts per Million

28 HE_1160_VMAR_TM_2ndcolumn_FC20_kyoufutsu_P_CDCl3_ jdf 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1160_VMAR_TM_2ndc Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 20 OCT :43:35 Revision_time = 20 OCT :54:06 Current_time = 20 OCT :54: Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 21[dC] S X : parts per Million : 1H

29 9HE_1160_VMAR_TM_13C_CDCl3_ jdf Total_scans = 600 9HE_1160_VMAR_TM_13C_CDCl3_ jdf X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 50 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 21.6[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1160_VMAR_TM_13C_ Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 19 OCT :10:02 Revision_time = 19 OCT :51:11 Current_time = 19 OCT :54:33 Comment = single pulse decouple Dim_size = Dim_title = 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = X : parts per Million : 13C S X : parts per Million : 13C : parts per Million

30 9HE_1161_H2add_TM_P_CDCl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1161_H2add_TM_P_C Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 20 OCT :12:00 Revision_time = 20 OCT :15:45 Current_time = 20 OCT :16: Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 46 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 21.2[dC] S X : parts per Million : 1H

31 9HE_xx_H2add(datedori)_13C_P_CDCl3_ jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 21.6[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_xx_H2add(datedori Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 2 OCT :30:12 Revision_time = 4 OCT :17:28 Current_time = 4 OCT :18: Comment = single pulse decouple Dim_size = Dim_title = 13C X : parts per Million : 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 1000 S X : parts per Million : 13C : parts per Million

32 9HE_1201_protection(BOM)_TM_kyoufutsu2_P_CDCl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1201_protection(B Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 22 OCT :30:22 Revision_time = 23 OCT :42:16 Current_time = 23 OCT :43: Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 48 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 21.3[dC] S X : parts per Million : 1H

33 9HE_1201_protection(BOM)_TM_13C_CDCl3_ jdf 9HE_1201_protection(BOM)_TM_13C_CDCl3_ jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 21.3[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1201_protection(B Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 23 OCT :37:01 Revision_time = 23 OCT :38:28 Current_time = 23 OCT :41:34 Comment = single pulse decouple Dim_size = Dim_title = 13C X : parts per Million : 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 1000 S X : parts per Million : 13C : parts per Million

34 9HE_1202_azidation_column3_FC18_kyoufutsu_P_CDCl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1202_azidation_co Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 27 OCT :05:46 Revision_time = 27 OCT :10:34 Current_time = 27 OCT :11:15 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 21[dC] S X : parts per Million : 1H

35 9HE_1202_azidation_column2_FC5_13C_CDCl3_ jdf Total_scans = 500 9HE_1202_azidation_column2_FC5_13C_CDCl3_ jdf X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 21.2[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1202_azidation_co Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 26 OCT :52:33 Revision_time = 26 OCT :53:08 Current_time = 26 OCT :54:07 Comment = single pulse decouple Dim_size = Dim_title = 13C X : parts per Million : 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Clipped = TRUE Scans = 500 S X : parts per Million : 13C : parts per Million

36 9HE_1203_dePMB_TM_P_CDCl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1203_dePMB_TM_P_C Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 29 OCT :59:41 Revision_time = 29 OCT :03:41 Current_time = 29 OCT :04: Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 21.2[dC] S X : parts per Million : 1H

37 9HE_1203_dePMB_TM_13C_CDCl3_ jdf 9HE_1203_dePMB_TM_13C_CDCl3_ jdf Total_scans = 500 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 21.2[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1203_dePMB_TM_13C Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 29 OCT :16:06 Revision_time = 22 JAN :54:49 Current_time = 22 JAN :57:17 Comment = single pulse decouple Dim_size = Dim_title = 13C X : parts per Million : 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 500 S X : parts per Million : 13C : parts per Million

38 9HE_1204_deXN_TM_column3_hexEA53_FC16 18_kyofutsu_P_CDCl3_ jdf Filename = 9HE_1204_deXN_TM_colu Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 3 NOV :14:07 Revision_time = 3 NOV :17:10 Current_time = 3 NOV :17:31 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 16 Total_scans = 16 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 20.7[dC] S X : parts per Million : 1H

39 9HE_1204_deXN_TM_column4_hexEA53_kyoufutsu_13C_CDCl3_ jdf 9HE_1204_deXN_TM_column4_hexEA53_kyoufutsu_13C_CDCl3_ jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 21.1[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1204_deXN_TM_colu Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 3 NOV :48:28 Revision_time = 14 FEB :50:44 Current_time = 14 FEB :52:35 Comment = single pulse decouple Dim_size = Dim_title = 13C X : parts per Million : 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 1000 S X : parts per Million : 13C : parts per Million

40 9HE_0813_staudinger_TM_P_CDCl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_0813_staudinger_T Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 11 OCT :08:53 Revision_time = 14 MAR :39:16 Current_time = 14 MAR :39:44 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 16 Total_scans = 16 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 20.9[dC] S X : parts per Million : 1H

41 9HE_0813_Mosher_( )_TM_purified_kyoufutsu_P_CDCl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_0813_Mosher_( )_T Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 14 MAR :29:06 Revision_time = 14 MAR :35:12 Current_time = 14 MAR :35:57 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 46 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 20.1[dC] S X : parts per Million : 1H

42 9HE_0813_Mosher_(+)_TM_purified_P_CDCl3_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_0813_Mosher_(+)_T Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 16 OCT :54:47 Revision_time = 24 JAN :03:32 Current_time = 24 JAN :04:08 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 16 Total_scans = 16 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 48 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 20.7[dC] S X : parts per Million : 1H

43 9HE_12xx_HPLC_separation_kyoufutsu_MeCN_H2O_4_1_nakarai_mae_P_D2O_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_12xx_HPLC_separat Experiment = single_pulse.ex2 Solvent = D2O Creation_time = 24 DEC :39:35 Revision_time = 24 DEC :40:28 Current_time = 24 DEC :40:56 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 1 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 19.7[dC] S X : parts per Million : 1H

44 9HE_1208_H2add_TM_MeOHstandard_13C_D2O_ jdf Total_scans = 600 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 20.9[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1208_H2add_TM_MeO Experiment = single_pulse_dec Solvent = D2O Creation_time = 16 NOV :57:37 Revision_time = 16 NOV :58:52 Current_time = 16 NOV :00:02 Comment = single pulse decouple Dim_size = Dim_title = 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 600 S X : parts per Million : 13C : parts per Million

45 9HE_1308_H2add_Me_TM_P_D2O_ jdf sexp : 0.2[Hz] : 0.0[s] 2.99 Filename = 9HE_1308_H2add_Me_TM_ Experiment = single_pulse.ex2 Solvent = D2O Creation_time = 12 MAR :13:00 Revision_time = 12 MAR :18:28 Current_time = 12 MAR :19:33 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 32 Total_scans = 32 X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 19.5[dC] S X : parts per Million : 1H

46 9HE_1236_H2add_Me_TM_13C_D2O_ jdf Total_scans = 7000 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 20.1[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1236_H2add_Me_TM_ Experiment = single_pulse_dec Solvent = D2O Creation_time = 4 MAR :13:12 Revision_time = 13 MAR :54:12 Current_time = 13 MAR :55:47 Comment = single pulse decouple Dim_size = Dim_title = 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 7000 S X : parts per Million : 13C : parts per Million

47 9HE_1236_H2add_diMe_TM_kyoufutsu_P_D2O_ jdf sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1236_H2add_diMe_T Experiment = single_pulse.ex2 Solvent = D2O Creation_time = 4 MAR :08:26 Revision_time = 14 MAR :49:09 Current_time = 14 MAR :49:40 Comment = single_pulse Dim_size = Dim_title = 1H X_acq_duration = [s] X_domain = 1H X_freq = [MHz] X_offset = 5[ppm] X_points = X_prescans = 1 X_resolution = [Hz] X_sweep = [kHz] Tri_domain = 1H Tri_freq = [MHz] Tri_offset = 5[ppm] Scans = 16 Total_scans = X_90_width = 10[us] X_acq_time = [s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 48 Relaxation_delay = 5[s] Repetition_time = [s] Temp_get = 19.9[dC] S X : parts per Million : 1H

48 9HE_1236_H2add_diMe_TM_13C_D2O_ jdf Total_scans = 5000 X_90_width = 8.9[us] X_acq_time = [s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = [us] Irr_atn_dec = [dB] Irr_atn_noe = [dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = [s] Temp_get = 20.1[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1236_H2add_diMe_T Experiment = single_pulse_dec Solvent = D2O Creation_time = 4 MAR :07:28 Revision_time = 4 MAR :11:39 Current_time = 4 MAR :13:49 Comment = single pulse decouple Dim_size = Dim_title = 13C X_acq_duration = [s] X_domain = 13C X_freq = [MHz] X_offset = 100[ppm] X_points = X_prescans = 4 X_resolution = [Hz] X_sweep = 31.25[kHz] Scans = 5000 S X : parts per Million : 13C : parts per Million