Desymmetrization of 2,4,5,6-Tetra-O-benzyl-D-myo-inositol for the Synthesis of Mycothiol

Desymmetrization of 2,4,5,6-Tetra--benzyl-D-myo-inositol for the Synthesis of Mycothiol Chuan-Chung Chung, Medel Manuel L. Zulueta, Laxmansingh T. Padiyar, and Shang-Cheng Hung* Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei 11529, Taiwan and Department of Applied Chemistry, National Chiao Tung University, 1001, Ta Hsueh Road, Hsinchu 300 Taiwan SUPPRTING INFRMATIN General Procedures. Dichloromethane, tetrahydrofuran (THF), and acetonitrile were purified and dried from a safe purification system filled with anhydrous Al 2 3. Flash column chromatography was carried out on Silica Gel 60 (230-400 mesh, E. Merk). TLC was performed on pre-coated glass plates of Silica Gel 60 F254 (0.25 mm, E. Merck); detection was executed by spraying with a solution of Ce(NH 4 ) 2 (N 3 ) 6, (NH 4 ) 6 Mo 7 24, and H 2 S 4 in water and subsequent heating on a hot plate. 1 H and 13 C NMR spectra were recorded on 600 MHz spectrometer. Chemical shifts are in ppm from Me 4 Si, calibrated using the residual proton and carbon of the deuterated solvent. Proton peak assignments were performed using 2D NMR techniques ( 1 H- 1 H CSY, HMQC and NESY); the hydrogen multiplicity of carbon peaks were determined using DEPT experiments. Bn Bn Bn Bn H H 7 Cl, DMAP pyr., 40 C, 24 h Bn Bn Bn Bn H 6: 69% + Bn Bn Bn Bn H 8: 24% + Bn Bn Bn Bn 9: 0% S1

2,4,5,6-tetra--benzyl-3--(1S)-ketopinyl-D-myo-inositol (6). (1S)-Ketopinyl chloride (21 mg, 0.104 mmol) was added to a solution of the 1,3-diol 7 (51 mg, 0.094 mmol) and N,Ndimethyl-4-aminopyridine (DMAP, 1 mg, 0.009 mmol) in anhydrous pyridine (2 ml) at 40 C under nitrogen atmosphere. After stirring for 24 hours at the same temperature, water (5 ml) was added to the mixture followed by extraction with CH 2 Cl 2 (3 10 ml). The combined organic layer was dried over anhydrous MgS 4, filtered, and concentrated in vacuo. Purification of the residue via flash column chromatography (ethyl acetate/hexanes = 1/4) on silica gel gave compound 6 (46 mg, 69%), together with its regioisomer 8 (16 mg, 24 %). [ ] 28 D +5.1 (c 3.0, CHCl 3 ); IR (CHCl 3 ) 3449, 3030, 2954, 2883, 1751, 1721, 1453 cm 1 ; 1 H NMR (600 MHz, CDCl 3 ) 7.36 7.31 (m, 8H, Ar-H), 7.30 7.25 (m, 9H, Ar-H), 7.24 7.21 (m, 3H, Ar-H), 5.05 (dd, J = 10.3, 2.5 Hz, 1H, H-3), 4.90 (d, J = 11.2 Hz, 1H, CH 2 Ar), 4.86 4.79 (m, 4H, CH 2 Ar), 4.76 4.73 (m, 3H, CH 2 Ar), 4.12 (t, J = 2.3 Hz, 1H, H-2), 4.10 (t, J = 9.5 Hz, 1H, H-4), 3.84 (t, J = 9.5 Hz, 1H, H-6), 3.65 (dd, J = 9.6, 2.2 Hz, 1H, H-1), 3.58 (t, J = 9.2 Hz, 1H, H-5), 2.50 (dt, J = 18.4, 3.6 Hz, 1H, CH 2 ), 2.34 2.27 (m, 1H, CH 2 ), 2.15 (brs, 1H, 1- H), 2.05 (t, J = 4.4 Hz, 1H, CH), 1.98 1.90 (m, 2H, CH 2 ), 1.81 1.75 (m, 1H, CH 2 ), 1.39 1.33 (m, 1H, CH 2 ), 1.13 (s, 3H, CH 3 ), 0.94 (s, 3H, CH 3 ); 13 C NMR (150 MHz, CDCl 3 ) 210.2 (C), 169.5 (C), 138.6 (C), 138.3 (C 2), 138.2 (C), 128.5 (CH 2), 128.3 (CH 2), 128.2 (CH 2), 128.1 (CH 2), 128.0 (CH 2), 127.9 (CH), 127.8 (CH 2), 127.6 (CH), 127.5 (CH), 127.4 (CH 2), 127.38 (CH 2), 127.31 (CH), 83.7 (CH), 81.8 (CH), 79.3 (CH), 78.3 (CH), 75.7 (CH 2 ), 75.5 (CH 2 ), 75.2 (CH 2 ), 74.9 (CH 2 ), 73.9 (CH), 72.2 (CH), 68.1 (C), 49.2 (C), 44.3 (CH), 43.8 (CH 2 ), 26.5 (CH 2 ), 26.3 (CH 2 ), 21.3 (CH 3 ), 19.6 (CH 3 ); HRMS (ESI, MNa + ) calcd for C 44 H 48 8 Na 727.3247, found 727.3244. 2,4,5,6-tetra--benzyl-1--(1S)-ketopinyl-D-myo-inositol (8). [ ] 28 D +4.4 (c 5.0, CHCl 3 ); IR (CHCl 3 ) 3462, 3031, 2954, 2883, 1752, 1724, 1454 cm 1 ; 1 H NMR (600 MHz, CDCl 3 ) 7.36 7.34 (m, 4H, Ar-H), 7.34 7.31 (m, 4H, Ar-H), 7.30 7.24 (m, 12H, Ar-H), 5.06 (dd, J = 10.3, 2.5 Hz, 1H, H-1), 4.90 (d, J = 11.2 Hz, 1H, CH 2 Ar), 4.89 (d, J = 11.4 Hz, 1H, CH 2 Ar), 4.87 4.82 (m, 3H, CH 2 Ar), 4.80 4.75 (m, 3H, CH 2 Ar), 4.15 (t, J = 2.5 Hz, 1H, H-2), 4.10 (t, J = 9.8 Hz, 1H, H-6), 3.84 (t, J = 9.5 Hz, 1H, H-4), 3.65 (dd, J = 9.7, 2.6 Hz, 1H, H-3), 3.57 (t, J = 9.2 Hz, 1H, H-5), 2.50 (dt, J = 18.4, 3.4 Hz, 1H, CH 2 ), 2.20 2.15 (m, 2H, CH 2, 1-H), 2.04 (t, J = 4.3 Hz, 1H, CH), 1.93 1.87 (m, 2H, CH 2 ), 1.78 1.72 (m, 1H, CH 2 ), 1.37 1.32 (m, 1H, CH 2 ), 1.18 (s, 3H, CH 3 ), 0.97 (s, 3H, CH 3 ); 13 C NMR (150 MHz, CDCl 3 ) 210.5 (C), 169.2 (C), 138.8 (C), 138.4 (C), 138.3 (C), 138.2 (C), 128.5 (CH 2), S2

128.3 (CH 2), 128.26 (CH 2), 128.22 (CH 2), 128.1 (CH 2), 127.8 (CH 2), 127.7 (CH), 127.6 (CH 2), 127.5 (CH), 127.4 (CH), 127.3 (CH 2), 83.5 (CH), 82.0 (CH), 79.5 (CH), 78.3 (CH), 75.8 (CH 2 ), 75.5 (CH 2 ), 75.3 (CH 2 ), 75.2 (CH 2 ), 73.7 (CH), 72.2 (CH), 67.8 (C), 48.9 (C), 44.0 (CH), 43.8 (CH 2 ), 26.3 (CH 2 ), 26.2 (CH 2 ), 21.0 (CH 3 ), 19.5 (CH 3 ); HRMS (ESI, MNa + ) calcd for C 44 H 48 8 Na 727.3247, found 727.3242. 2,4,5,6-tetra--benzyl-1,3-di--(1S)-ketopinyl-D-myo-inositol (9). [ ] 28 D +31.7 (c 1.8, CHCl 3 ); IR (CHCl 3 ) 3030, 2966, 2883, 1753, 1727, 1454 cm 1 ; 1 H NMR (600 MHz, CDCl 3 ) 7.46 (d, J = 7.4 Hz, 2H, Ar-H), 7.44 7.37 (m, 4H, Ar-H), 7.36 7.33 (m, 7H, Ar-H), 7.32 7.28 (m, 5H, Ar-H), 7.27 7.23 (m, 2H, Ar-H), 5.26 (dd, J = 10.1, 2.0 Hz, 1H, H-1), 5.24 (dd, J = 10.1, 2.0 Hz, 1H, H-3), 4.99 (d, J = 11.2 Hz, 1H, CH 2 Ar), 4.95 (d, J = 10.7 Hz, 1H, CH 2 Ar), 4.94 4.83 (m, 1H, CH 2 Ar), 4.92 (d, J = 10.7 Hz, 1H, CH 2 Ar), 4.88 (s, 2H, CH 2 Ar), 4.85 (d, J = 11.2 Hz, 1H, CH 2 Ar), 4.84 (d, J = 11.2 Hz, 1H, CH 2 Ar), 4.32 (s, 1H, H-2), 4.27 4.21 (m, 2H, H-4, H-6), 3.75 (t, J = 9.3 Hz, 1H, H-5), 2.58 2.53 (m, 2H, CH 2 ), 2.40 2.34 (m, 1H, CH 2 ), 2.26 2.19 (m, 1H, CH 2 ), 2.12 2.08 (m, 2H, CH), 2.04 1.93 (m, 2H, CH 2 ), 1.97 (dd, J = 18.4, 4.9 Hz, 2H, CH 2 ), 1.86 1.76 (m, 2H, CH 2 ), 1.45 1.35 (m, 2H, CH 2 ), 1.25 (s, 3H, CH 3 ), 1.21 (s, 3H, CH 3 ), (s, 6H, CH 3 ); 13 C NMR (150 MHz, CDCl 3 ) 210.1 (C), 209.7 (C), 168.9 (C), 168.8 (C), 138.8 (C), 138.3 (C), 138.2 (C), 138.0 (C), 128.1 (CH 2), 128.0 (CH 2), 127.98 (CH 2), 127.96 (CH 2), 127.7 (CH 2), 127.4 (CH), 127.3 (CH 2), 127.2 (CH), 127.1 (CH 2), 127.08 (CH 2), 127.06 (CH 2), 83.5 (CH), 79.2 (CH), 79.0 (CH), 77.4 (CH), 75.8 (CH 2 ), 75.2 (CH 2 ), 75.1 (CH 2 ), 74.9 (CH 2 ), 73.1 (CH), 73.0 (CH), 67.8 (C), 67.5 (C), 49.0 (C), 48.8 (C), 44.1 (CH), 43.8 (CH), 43.6 (CH 2 2), 26.4 (CH 2 2), 26.2 (CH 2 2), 21.0 (CH 3 ), 20.9 (CH 3 ), 19.5 (CH 3 ), 19.4 (CH 3 ); HRMS (ESI, MNa + ) calcd for C 54 H 60 10 Na 891.4084, found 891.4075. 2-NAP p-brbn TBDPS + N 3 STol 5 Bn Bn Bn Bn H 6 NIS, TfH CH 2 Cl 2, 60 C 3 h, 84% 2-NAP p-brbn TBDPS Bn Bn N 3 Bn Bn 10 1--[2-Azido-3--(4-bromobenzyl)-6--tert-butyldiphenylsilyl-2-deoxy-4--(2- naphthylmethyl)- -D-glucopyranosyl]-2,4,5,6-tetra--benzyl-3--(1S)-ketopinyl-D-myoinositol (10). A solution of the donor 5 (150 mg, 0.175 mmol) and the acceptor 6 (82 mg, 0.116 mmol) in anhydrous dichloromethane (4 ml) containing freshly dried 4 Å molecular sieves (348 mg) was stirred at room temperature for 30 minutes under nitrogen atmosphere. S3

The solution was cooled to 60 C, and N-iodosuccinimide (NIS, 31 mg, 0.140 mmol) was added to the reaction flask followed by TfH (5 L, 0.058 mmol) 10 min later, and the solution was kept stirring at 60 C for 3 hours. Saturated NaHC 3 (10 ml) and 10% Na 2 S 2 3(aq) (10 ml) were added to quench the reaction, and the mixture was filtered through Celite and extracted with CH 2 Cl 2 (3 20 ml). The combined organic layer was dried over anhydrous MgS 4, filtered, and concentrated in vacuo. Purification of the residue via flash column chromatography (ethyl acetate/hexanes = 1/6) on silica gel furnished the desired adduct 10 (141 mg, 84%). [ ] 28 D +1.0 (c 2.5, CHCl 3 ); IR (CHCl 3 ) 3030, 2930, 2858, 2108, 1753, 1726, 1454 cm 1 ; 1 H NMR (600 MHz, CDCl 3 ) 7.82 7.79 (m, 1H, Ar-H), 7.74 7.70 (m, 2H, Ar-H), 7.68 7.63 (m, 4H, Ar-H), 7.57 7.55 (m, 1H, Ar-H), 7.48 7.45 (m, 2H, Ar-H), 7.41 7.25 (m, 21H, Ar-H), 7.23 7.16 (m, 8H, Ar-H), 7.14 7.11 (m, 2H, Ar-H), 5.42 (d, J = 3.6 Hz, 1H, H-1'), 5.00 (d, J = 10.6 Hz, 1H, CH 2 Ar), 4.97 (dd, J = 10.4, 2.3 Hz, 1H, H-3), 4.95 (d, J = 10.6 Hz, 1H, CH 2 Ar), 4.90 (d, J = 11.1 Hz, 1H, CH 2 Ar), 4.86 4.79 (m, 4H, CH 2 Ar), 4.78 4.70 (m, 4H, CH 2 Ar), 4.67 (d, J = 11.0 Hz, 1H, CH 2 Ar), 4.15 (t, J = 9.7, 1H, H-6), 4.08 (t, J = 9.7 Hz, 1H, H-4), 3.98 (t, J = 2.3 Hz, 1H, H-2), 3.94 (dd, J = 11.7, 2.8 Hz, 1H, H-6'a), 3.91 3.86 (m, 3H, H-3', H-5', H-6'b), 3.78 3.72 (m, 2H, H-5, H-4'), 3.59 (dd, J = 9.4, 2.3 Hz, 1H, H-1), 3.36-3.33 (m, 1H, H-2'), 2.47 (dt, J = 18.3, 3.4 Hz, 1H, CH 2 ), 2.28 2.22 (m, 1H, CH 2 ), 2.01 (t, J = 4.4 Hz, 1H, CH), 1.95 1.87 (m, 2H, CH 2 ), 1.75 1.69 (m, 1H, CH 2 ), 1.36 1.30 (m, 1H, CH 2 ), 1.07 (s, 9H, t-bu), 1.06 (s, 3H, CH 3 ), 0.89 (s, 3H, CH 3 ); 13 C NMR (150 MHz, CDCl 3 ) 209.9 (C), 169.3 (C), 138.6 (C 2), 138.4 (C), 138.2 (C), 136.8 (C), 135.9 (CH 2), 135.6 (CH 2), 135.4 (CH), 133.5 (CH), 133.2 (CH), 133.0 (CH), 132.9 (CH), 131.5 (CH 2), 129.7 (CH), 129.6 (CH), 129.5 (CH 2), 128.4 (CH 2), 128.3 (CH 2), 128.2 (CH 2), 128.1 (CH 2), 127.5 (CH 2), 127.4 (CH), 127.3 (CH), 127.28 (CH 2), 127.24 (CH), 127.1 (CH 2), 126.3 (CH), 126.1 (CH), 125.9 (CH), 125.7 (CH), 121.7 (C), 98.3 (CH), 84.0 (CH), 81.5 (CH), 80.2 (CH), 79.1 (CH), 78.8 (CH), 78.1 (CH), 76.8 (CH), 75.8 (CH 2 ), 75.3 (CH 2 2), 75.2 (CH 2 ), 74.8 (CH 2 ), 74.5 (CH 2 ), 73.6 (CH), 72.8 (CH) 67.9 (C), 63.6 (CH), 62.1 (CH 2 ), 49.1 (C), 44.3 (CH), 43.8 (CH 2 ), 26.9 (CH 3 3), 26.6(CH 2 ), 26.3 (CH 2 ), 21.2 (CH 3 ), 19.6 (CH 3 ), 19.3 (C); HRMS (ESI, MNa + ) calcd for C 84 H 88 N 3 12 NaSi 1460.5218, found 1460.5209. S4

2-NAP p-brbn TBDPS Bn Bn N 3 Bn Bn 10 NaH EtH/CH 2 Cl 2 60 C, 30 min 95% 2-NAP p-brbn TBDPS Bn Bn N 3 Bn Bn H 11 1--[2-Azido-3--(4-bromobenzyl)-6--tert-butyldiphenylsilyl-2-deoxy-4--(2- naphthylmethyl)- -D-glucopyranosyl]-2,4,5,6-tetra--benzyl-D-myo-inositol (11). Sodium hydroxide (54 mg, 1.361 mmol) was added to a solution of compound 10 (98 mg, 0.068 mmol) in a mixed EtH (4 ml) and CH 2 Cl 2 (1 ml) at room temperature. The mixture was stirred at 60 C for 30 min, and the reaction solution was concentrated in vacuo, and extracted with ethyl acetate (3 20 ml). The combined organic layer was dried over anhydrous MgS 4, filtered, and concentrated in vacuo. Purification of this residue via flash column chromatography (ethyl acetate/hexanes = 1/3) on silica gel gave compound 11 (82 mg, 95%). The water layer was acidified with 6 M H 2 S 4 to ph 2, extracted with ethyl acetate (3 10 ml), and dried over anhydrous MgS 4, filtered, and concentrated in vacuo to recover (1S)-ketopinic acid (11 mg, 88%). [ ] 28 D +5.5 (c 4.2, CHCl 3 ); IR (CHCl 3 ) 3447, 3030, 2929, 2857, 2107, 1454 cm 1 ; 1 H NMR (600 MHz, CDCl 3 ) 7.85 7.82 (m, 1H, Ar-H), 7.76 7.72 (m, 2H, Ar-H), 7.69 7.63 (m, 4H, Ar-H), 7.59 7.57 (m, 1H, Ar-H), 7.52 7.48 (m, 2H, Ar-H), 7.44 7.23 (m, 29H, Ar-H), 7.20 7.17 (m, 2H, Ar-H), 5.41 (d, J = 3.7 Hz, 1H, H- 1'), 5.04 (d, J = 10.4 Hz, 1H, CH 2 Ar), 4.98 (d, J = 10.4 Hz, 1H, CH 2 Ar), 4.94 4.86 (m, 5H, CH 2 Ar), 4.82 4.73 (m, 5H, CH 2 Ar), 4.15 (t, J = 2.1 Hz, 1H, H-2), 3.99 3.96 (m, 1H, H-3'), 3.92 (t, J = 9.3 Hz, 1H, H-6), 3.88 3.80 (m, 4H, H6'a, H6'b, H-4, H-5'), 3.77 3.71 (m, 2H, H4', H-1), 3.52 (t, J = 9.3, 1H, H-5), 3.48 (dd, J = 9.7, 2.5 Hz, 1H, H-3), 3.36 (dd, J = 10.4, 3.7 Hz, 1H, H-2'), 1.07 (s, 9H, t-bu); 13 C NMR (150 MHz, CDCl 3 ) 138.6 (C), 138.5 (C), 138.4 (C), 136.7 (C), 135.8 (CH 2), 135.6 (CH 2), 135.3 (C), 133.2 (C), 133.1 (C), 133.0 (C), 132.9 (C), 131.5 (CH), 129.7 (CH), 129.73 (CH), 129.6 (CH), 128.5 (CH), 128.4 (CH 2), 128.2 (CH), 128.1 (CH), 127.9 (CH), 127.8 (CH), 127.71 (CH), 127.68 (CH), 127.61 (CH 2), 127.5 (CH), 126.3 (CH), 126.2 (CH), 125.9 (CH), 125.6 (CH), 121.8 (C), 98.8 (CH), 84.0 (CH), 81.9 (CH), 81.8 (CH), 80.1 (CH), 79.5 (CH), 78.4 (CH), 77.2 (CH), 75.7 (CH 2 ), 75.5 (CH 2 ), 75.4 (CH 2 ), 75.1 (CH 2 ), 75.0 (CH 2 ), 74.5 (CH 2 ), 72.9 (CH), 72.4 (CH), 63.5 (CH), 62.6 (CH 2 ), 26.9 (CH 3 3), 19.2 (C); HRMS (ESI, MNa + ) calcd for C 74 H 76 N 3 10 NaSi 1296.4381, found 1296.4376. S5

TBDPS 2-NAP p-brbn TBDPS N STol 3 5 + Bn Bn Bn Bn H H 7 NIS, TfH CH 2 Cl 2, 4 Å MS 60 to 20 C, 3 h + 2-NAP p-brbn 2-NAP p-brbn Bn Bn N 3 Bn Bn H 11: 41% TBDPS Bn N 3 Bn 12: 49% H Bn Bn Direct D-glucosaminylation of compound 7. A solution of the donor 5 (119 mg, 0.139 mmol) and acceptor 7 (50 mg, 0.092 mmol) in anhydrous dichloromethane (4 ml) containing freshly dried 4 Å molecular sieves (1.69 g) was stirred at room temperature for 30 min under nitrogen atmosphere. Then, NIS (25 mg, 0.111 mmol) was added and the resultant solution was cooled to 60 C. After stirring for 20 minutes, TfH (40 L, 0.046 mmol) was added to the mixture, and the solution was gradually warmed up to 20 C for 3 hours. Saturated NaHC 3 (10 ml) and 10% Na 2 S 2 3(aq) (10 ml) were added to quench the reaction, and the mixture was filtered through Celite, and extracted with CH 2 Cl 2 (3 20 ml). The combined organic layer was dried over anhydrous MgS 4, filtered, and concentrated in vacuo. Purification of the residue via flash column chromatography (ethyl acetate/hexanes = 1/3) on silica gel gave compound 11 (48 mg, 41%), together with its regioisomer 12 (58 mg, 49%). 3--[2-Azido-3--(4-bromobenzyl)-6--tert-butyldiphenylsilyl-2-deoxy-4--(2- naphthylmethyl)- -D-glucopyranosyl]-2,4,5,6-tetra--benzyl-D-myo-inositol (12). [ ] 28 D +2.6 (c 4.2, CHCl 3 ); IR (CHCl 3 ) 3456, 3064, 3030, 2929, 2857, 2107, 1454 cm 1 ; 1 H NMR (600 MHz, CDCl 3 ) 7.88 7.86 (m, 1H, Ar-H), 7.78 7.72 (m, 2H, Ar-H), 7.69 7.62 (m, 4H, Ar-H), 7.57 7.55 (m, 1H, Ar-H), 7.53 7.50 (m, 2H, Ar-H), 7.45 7.37 (m, 8H, Ar-H), 7.36 7.24 (m, 20H, Ar-H), 7.22 7.20 (m, 1H, Ar-H), 7.18 7.15 (m, 2H, Ar-H), 5.12 (d, J = 3.6 Hz, 1H, H-1'), 5.01 (d, J = 11.2 Hz, 1H, CH 2 Ar), 4.93 4.90 (m, 2H, CH 2 Ar), 4.89 4.84 (m, 2H, CH 2 Ar), 4.83 4.74 (m, 7H, CH 2 Ar), 4.15 (t, J = 2.1 Hz, 1H, H-2), 4.08 4.02 (m, 3H, H-6, H- 5', H-3'), 3.88 (t, J = 9.5, 1H, H-4), 3.85 3.79 (m, 3H, H-6'a, H-6'b, H-5), 3.67 (dd, J = 10.0, 2.1 Hz, 1H, H-4'), 3.49 (dd, J = 9.8, 2.1 Hz, 1H, H-1), 3.47 3.42 (m, 2H, H-2', H-3), 2.28 (brs, 1H, 1-H), (s, 9H, t-bu); 13 C NMR (150 MHz, CDCl 3 ) 138.5 (C), 138.4 (C), 138.1 (C), 136.7 (C), 135.8 (CH 2), 135.5 (CH 2), 133.4 (C), 133.2 (C), 133.1 (C), 132.9 (C), 131.5 (CH), 129.7 (CH), 129.6 (CH), 128.5 (CH), 128.3 (CH 2), 128.2 (CH), 128.0 (CH), 127.9 (CH 2), 127.7 (CH), 127.64 (CH), 127.60 (CH), 127.5 (CH), 127.4 (CH), S6

126.1 (CH), 126.0 (CH), 125.9 (CH), 125.6 (CH), 121.8 (C), 93.7 (CH), 83.8 (CH), 81.5 (CH), 80.7 (CH), 80.1 (CH), 78.4 (CH), 76.0 (CH 2 ), 75.6 (CH 2 ), 75.3 (CH 2 ), 75.0 (CH 2 ), 74.8 (CH), 74.7 (CH 2 ), 74.5 (CH 2 ), 74.3 (CH), 72.5 (CH), 71.9 (CH), 63.4 (CH), 62.4 (CH 2 ), 26.9 (CH 3 3), 19.3 (C); HRMS (ESI, MNa + ) calcd for C 74 H 76 N 3 10 NaSi 1296.4381, found 1296.4379. 2-NAP p-brbn TBDPS Bn Bn N 3 Bn N 3 H 11 TBAF 95% 2-NAP p-brbn H Bn Bn N 3 H Bn H S1 1--[2-Azido-3--(4-bromobenzyl)-2-deoxy-4--(2-naphthylmethyl)- -Dglucopyranosyl]-2,4,5,6-tetra--benzyl-D-myo-inositol (S1). Tetra-n-butylammonium fluoride (TBAF, 1 M solution in THF, 0.183 ml, 0.183 mmol) was added to a mixture of compound 11 (78 mg, 0.061 mmol) in THF (1 ml) at room temperature. After stirring for 24 hours, water (5 ml) was added to the mixture followed by extraction with ethyl acetate (3 10 ml), and the combined organic layer was washed with brine, dried over anhydrous MgS 4, filtered, and concentrated in vacuo. Purification of the residue via flash column chromatography (ethyl acetate/hexanes = 1/1) on silica gel furnished the desired diol S1 (60 mg, 95%). [ ] 28 D +9.7 (c 9.4, CHCl 3 ); IR (CHCl 3 ) 3444, 3030, 2922, 2875, 2107, 1454 cm 1 ; 1 H NMR (600 MHz, CDCl 3 ) 7.94 7.86 (m, 3H, Ar-H), 7.80 7.78 (m, 1H, Ar-H), 7.61 7.57 (m, 2H, Ar-H), 7.56 7.53 (m, 2H, Ar-H), 7.49 7.45 (m, 7H, Ar-H), 7.45-7.35 (m, 14H, Ar-H), 7.26 7.23 (m, 2H, Ar-H), 5.51 (d, J = 3.4 Hz, 1H, H-1'), 5.13 (d, J = 10.6 Hz, 1H, CH 2 Ar), 5.09 (d, J = 10.6 Hz, 1H, CH 2 Ar), 5.06 (d, J = 11.5 Hz, 1H, CH 2 Ar), 5.03 4.98 (m, 4H, CH 2 Ar), 4.95 4.91 (m, 2H, CH 2 Ar), 4.90 4.86 (m, 3H, CH 2 Ar), 4.27 (t, J = 9.5 Hz, 1H, H-6), 4.11 4.04 (m, 2H, H-2, H-3'), 3.96 (t, J = 9.5, 1H, H-4), 3.92 3.83 (m, 3H, H-5', H-6'a, H-1), 3.79 (dd, J = 11.9, 3.5 Hz, 1H, H-6'b), 3.74 (t, J = 9.1 Hz, 1H, H-4'), 3.69 (dd, J = 9.7, 2.3 Hz, 1H, H-3), 3.62 (t, J = 9.2 Hz, 1H, H-5), 3.37 (dd, J = 10.3, 3.4 Hz, 1H, H-2'), 2.34 (brs, 2H, H); 13 C NMR (150 MHz, CDCl 3 ) 138.5 (C), 138.4 (C), 138.3 (C), 138.2 (C), 136.6 (C), 135.1 (C), 133.1 (C), 132.9 (C), 131.4 (CH 2), 129.4 (CH 2), 128.43 (CH 2), 128.39 (CH 2), 128.31 (CH 2), 128.28 (CH 2), 128.18 (CH), 127.9 (CH 2), 127.78 (CH), 127.74 (CH 2), 129.71 (CH), 127.6 (CH), 127.55 (CH 2), 127.52 (CH), 127.4 (CH), 127.3 (CH 2), 126.3 (CH), 126.2 (CH), 126.0 (CH), 125.5 (CH), 121.7 (C), 98.7 (CH), 83.9 (CH), 81.7 (CH), 81.6 (CH), 79.7 (CH), 79.5 (CH), 77.9 (CH), 77.0 (CH), 75.6 (CH 2 ), 75.4 (CH 2 ), 75.3 (CH 2 ), 74.94 (CH 2 ), 74.92 (CH 2 ), 74.3 (CH 2 ), 72.4 (CH), 72.2 S7

(CH), 63.2 (CH), 61.2 (CH 2 ); HRMS (ESI, MNa + ) calcd for C 58 H 58 N 3 10 Na 1058.3203, found 1058.3206. 2-NAP p-brbn H Bn Bn Pd(H) 2, H 2, HCl (aq) N 3 Bn Bn H MeH, 98% S1 H H HCl H H 2 N H 4 H H H H 1--(2-amino-2-deoxy- -D-glucopyranosyl)-D-myo-inositol hydrochloride (4). A solution of compound S1 (89 mg, 0.086 mmol) and 20% Pd(H) 2 (536 mg) in a mixed MeH (3 ml), H 2 (0.5 ml) and 0.1 N of HCl aq (0.1 ml) was purged 3 times with a balloon filled with hydrogen gas, and then stirred under hydrogen balloon for 3 days. The reaction was then filtered through Celite, and the filtrate was concentrated in vacuo. After concentration and desalting through a Sephadex G-10 column eluted with water, the collected fraction was concentrated to afford the pseudodisaccharide 4 (32 mg, 98%) as a colorless oil. [ ] 28 D +97.7 (c 1.6, H 2 ); 1 H NMR (600 MHz, D 2 ) 5.37 (d, J = 3.7 Hz, 1H, H-1'), 4.15 (t, J = 2.5 Hz, 1H, H-2), 3.90 3.86 (m, 1H, H-3'), 3.84 3.78 (m, 2H, H-6'a, H-5'), 3.75 3.70 (m, 2H, H-6'b, H-6), 3.65 (dd, J = 10.1, 2.7 Hz, 1H, H-1), 3.57 (t, J = 9.5 Hz, 1H, H-4), 3.50 (dd, J = 10.0, 2.6 Hz, 1H, H-3), 3.45 (t, J = 9.5 Hz, 1H, H-4'), 3.31 (dd, J = 10.7, 3.7 Hz, 1H, H- 2'), 3.26 (t, J = 9.4 Hz, 1H, H-5); 13 C NMR (150 MHz, D 2 ) 97.3 (CH), 78.9 (CH), 74.1 (CH), 72.7 (CH), 72.0 (CH), 71.9 (CH), 71.7 (CH), 70.9 (CH), 69.6 (CH), 69.4 (CH), 60.3 (CH 2 ), 54.3 (CH); HRMS (ESI, MH + ) calcd for C 12 H 24 N 10 342.1400, found 342.1397. This compound has also been previously characterized. 1,2 H H HCl H H 2 N H 4 H H H H NHBoc SAc H 2 C 13 HATU, DIPEA, DMF, 12 h, 78% H H AcS H H HN NHBoc 14 H H H H 1--[2-deoxy-2-(N-tert-butyloxycarbonyl-S-acetyl-L-cysteinyl)amino- -Dglucopyranosyl]-D-myo-inositol (14). To a solution of 4 (21 mg, 0.056 mmol) and 13 (29 mg, 0.111 mmol) in anhydrous N,N-dimethylformamide (DMF, 2 ml) was added -(7- azabenzotriazol-1-yl)-n,n,n',n'-tetramethyluronium hexafluorophosphate (HATU, 42 mg, 0.111 mmol) and diisopropylethylamine (DIPEA, 29 μl, 0.167 mmol) at 4 C under nitrogen atmosphere. After stirring for 12 hours at room temperature, the reaction was concentrated in vacuo. Purification of the residue via flash column chromatography (CH 2 Cl 2 /methanol/acetic S8

acid = 80/20/1) on silica gel gave compound 14 (26 mg, 78%). [ ] 27 D +9.3 (c 1.0, H 2 ); 1 H NMR (600 MHz, D 2 ) 5.12 (d, J = 4.4 Hz, 1H), 4.31 (dd, J = 8.2, 4.7 Hz, 1H), 4.20 4.16 (brs, 1H), 3.94 (dd, J = 10.7, 3.4 Hz, 1H), 3.87 3.79 (m, 3H), 3.78 3.73 (m, 2H), 3.60 (t, J = 9.6 Hz, 1H), 3.57 (dd, J = 10.3, 2.5 Hz, 1H), 3.52 (dd, J = 9.9, 2.6 Hz, 1H), 3.46 (t, J = 9.5 Hz, 1H), 3.39 (dd, J = 14.2, 4.7 Hz, 1H), 3.25 (t, J = 9.4 Hz, 1H), 3.11 (dd, J = 14.2, 8.6 Hz, 1H), 2.38 (s, 3H), 1.42 (s, 9H); 13 C NMR (150 MHz, D 2 ) 200.0 (C), 172.5 (C), 157.4 (C), 99.1 (CH), 81.9 (C), 79.0 (CH), 74.2 (CH), 72.5 (CH), 72.1 (CH 2), 71.7 (CH), 71.0 (CH), 70.7 (CH), 70.0 (CH), 60.5 (CH 2 ), 54.1 (CH), 54.0 (CH), 30.7 (CH 2 ), 29.8 (CH 3 ), 27.5 (CH 3 3); HRMS (ESI, MNa + ) calcd for C 22 H 38 N 2 14 SNa 609.1941, found 609.1953. This compound has also been previously characterized. 2 H H H H H H HN H H 1. TFA 2. pyridine H H H H H H HN H H NHAc AcS NHBoc 14 HS 1 1--[2-deoxy-2-(N-acetyl-L-cysteinyl)amino- -D-glucopyranosyl]-D-myo-inositol (1). Cold trifluoroacetic acid (TFA, 0.4 ml) was added to compound 14 (5.3 mg, 0.009 mmol) and the mixture was stirred for 20 minutes at 4 C. The reaction was, then, concentrated in vacuo, and pyridine (0.6 ml) was added to the residue. After stirred for 30 minutes at room temperature, the reaction was concentrated in vacuo and azeotroped with water and toluene to obtain compound 1 (4.4 mg, 100%). [ ] 27 D +16.2 (c 0.5, H 2 ); 1 H NMR (600 MHz, D 2 ) 5.12 (d, J = 3.6 Hz, 1H), 4.51 (t, J = 6.1 Hz, 1H), 4.18 (t, J = 2.5 Hz, 1H), 3.97 (dd, J = 10.7, 3.7 Hz, 1H), 3.89 3.82 (m, 2H), 3.81 3.73 (m, 3H), 3.62 (t, J = 9.5 Hz, 1H), 3.57 (dd, J = 10.1, 2.8 Hz, 1H), 3.51 (dd, J = 9.9, 2.8 Hz, 1H), 3.46 (t, J = 9.5 Hz, 1H), 3.28 (t, J = 9.5 Hz, 1H), 2.92 (dd, J = 14.3, 5.3 Hz, 1H), 2.88 (dd, J = 14.3, 7.2 Hz, 1H), 2.05 (s, 3H); 13 C NMR (150 MHz, D 2 ) 174.4 (C), 172.0 (C), 99.2 (CH), 79.0 (CH), 74.2 (CH), 72.5 (CH), 72.1 (CH), 72.0 (CH), 71.7 (CH), 71.0 (CH), 70.8 (CH), 70.0 (CH), 60.5 (CH 2 ), 55.7 (CH), 53.8 (CH), 25.6 (CH 2 ), 21.7 (CH 3 ); HRMS (ESI, MNa + ) calcd for C 17 H 30 N 2 12 NaS 509.1417, found 509.1431. This compound has also been previously characterized. 2,3 References: (1) Jardine, M. A.; Spies, H. S. C.; Nkambule, C. M.; Gammon, D. W.; Steenkamp, D. J. Bioorg. Med. Chem. 2002, 10, 875 881. (2) Ajayi, K.; Thakur, V. V.; Lapo, R. C.; Knapp, S. rg. Lett. 2010, 12, 2630 2633. (3) Lee, S.; Rosazza, J. P. N. rg. Lett. 2004, 6, 365 368. S9

0.9440 1.1345 1.3585 1.3645 1.3818 1.7677 1.7832 1.7914 1.9067 1.9374 1.9446 1.9509 2.0405 2.0478 2.0551 2.3151 2.4848 2.5155 3.5644 3.5798 3.5951 3.6407 3.6444 3.6568 3.6604 3.8282 3.8440 3.8598 4.0865 4.1024 4.1142 4.1185 4.1224 4.7433 4.7583 4.8011 4.8029 4.8185 4.8212 4.8298 4.8377 4.8477 4.8561 4.8919 4.9106 5.0389 5.0430 5.0561 5.0602 7.2242 7.2271 7.2366 7.2397 7.2464 7.2537 7.2584 7.2655 7.2708 7.2745 7.2854 7.2971 7.3002 7.3036 7.3135 7.3184 7.3255 7.3329 7.3368 7.3444 7.3573 Bn H Bn Bn Bn NAME CC-80-15 EXPN 1 PRCN 1 Date_ 20110131 Time 16.36 PRBHD 5 mm CPTCI 1H- PULPRG zg TD 32768 SLVENT CDCl3 NS 20 SWH 8370.536 Hz FIDRES 0.255448 Hz AQ 1.9573919 sec RG 9 DW 59.733 usec TD0 1 NUC1 1H P1 7.93 usec PL1 4.20 db PL1W 5.82545519 W SF1 600.1336009 MHz SI 16384 SF 600.1300292 MHz LB 0 Hz 9 8 7 6 5 4 3 2 1 0 ppm 3.07 9.08 8.00 3.05 4.10 1.07 2.04 1.05 1.06 2.06 1.10 1.01 1.11 1.06 3.04 3.04 S10

210.17 169.49 127.31 127.38 127.46 127.55 127.59 127.82 127.85 128.06 128.16 128.28 128.33 128.53 138.26 138.38 138.64 68.14 72.23 73.86 74.94 75.23 75.46 75.71 76.79 77.00 77.21 78.31 79.34 81.75 83.67 43.82 44.33 49.18 19.62 21.29 26.27 26.55 NAME CC-80-15 EXPN 2 PRCN 1 Bn H Bn Bn Bn Date_ 20110201 Time 0.11 PRBHD 5 mm CPTCI 1H- PULPRG zgpg30 TD 131072 SLVENT CDCl3 NS 3000 SWH 39062.500 Hz FIDRES 0.298023 Hz AQ 1.6777716 sec RG 2050 DW 12.800 usec D11 0.03000000 sec TD0 3 NUC1 13C P1 10.00 usec PL1-1.82 db PL1W 122.22216797 W SF1 150.9201600 MHz ======== CHANNEL f2 ======== CPDPRG2 waltz16 NUC2 1H PCPD2 90.00 usec PL2 4.20 db PL12 25.30 db PL13 28.13 db PL2W 5.82545519 W PL12W 0.04522627 W PL13W 0.02356839 W SF2 600.1339008 MHz SI 65536 SF 150.9028205 MHz LB 3.00 Hz 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm S11

0.9655 1.1825 1.3383 1.3442 1.3512 1.7351 1.7425 1.7504 1.7584 1.8998 1.9067 1.9304 2.0342 2.0416 2.0488 2.1681 2.1726 2.1778 2.4875 2.4945 2.5181 3.5536 3.5690 3.5844 3.6423 3.6467 3.6585 3.6628 3.8209 3.8366 3.8525 4.0872 4.1034 4.1198 4.1463 4.1505 4.1547 4.7520 4.7705 4.7775 4.7966 4.8217 4.8397 4.8430 4.8482 4.8616 4.8661 4.8768 4.8862 4.8958 4.9048 5.0511 5.0552 5.0683 5.0724 7.2400 7.2558 7.2603 7.2675 7.2742 7.2788 7.2845 7.2898 7.2939 7.3015 7.3115 7.3248 7.3357 7.3524 7.3598 Bn Bn Bn Bn H NAME CCC-80-5 EXPN 1 PRCN 1 Date_ 20110427 Time 17.49 PRBHD 5 mm CPTCI 1H- PULPRG zg TD 32768 SLVENT CDCl3 NS 20 SWH 8370.536 Hz FIDRES 0.255448 Hz AQ 1.9573919 sec RG 6.35 DW 59.733 usec TD0 1 NUC1 1H P1 8.00 usec PL1 4.20 db PL1W 5.82545519 W SF1 600.1336009 MHz SI 16384 SF 600.1300292 MHz LB 0 Hz 10 9 8 7 6 5 4 3 2 1 ppm 12.00 4.07 4.01 3.02 3.05 1.17 1.01 1.07 1.06 1.10 2.05 1.04 1.07 3.05 3.08 1.02 S12

210.48 169.21 127.27 127.40 127.50 127.57 127.79 127.84 128.06 128.22 128.26 128.33 128.47 138.29 138.39 138.43 138.77 67.78 72.18 73.75 75.16 75.27 75.51 75.76 76.79 77.00 77.21 78.27 79.51 81.98 83.52 43.79 44.00 48.97 19.48 21.02 26.19 26.27 NAME CCC-80-5 EXPN 7 PRCN 1 Bn Bn Bn Bn H Date_ 20110428 Time 5.25 PRBHD 5 mm CPTCI 1H- PULPRG zgpg30 TD 131072 SLVENT CDCl3 NS 5000 SWH 39062.500 Hz FIDRES 0.298023 Hz AQ 1.6777716 sec RG 2050 DW 12.800 usec D11 0.03000000 sec TD0 5 NUC1 13C P1 10.00 usec PL1-1.82 db PL1W 122.22216797 W SF1 150.9201600 MHz ======== CHANNEL f2 ======== CPDPRG2 waltz16 NUC2 1H PCPD2 90.00 usec PL2 4.20 db PL12 25.22 db PL13 28.13 db PL2W 5.82545519 W PL12W 0.04602830 W PL13W 0.02356839 W SF2 600.1339008 MHz SI 65536 SF 150.9028253 MHz LB 3.00 Hz 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm S13

1.0455 1.2137 1.2533 1.3915 1.3970 1.4015 1.4082 1.4131 1.4189 1.4287 1.7925 1.8004 1.8169 1.8256 1.8410 1.8491 1.9526 1.9609 1.9833 1.9914 2.0914 2.0993 2.1057 2.1128 2.2290 2.3722 2.5436 2.5742 3.7390 3.7544 3.7699 4.2155 4.2317 4.2443 4.2600 4.3229 4.8354 4.8455 4.8540 4.8641 4.8751 4.9122 4.9301 4.9450 4.9628 4.9835 5.0022 5.2281 5.2315 5.2450 5.2483 5.2617 5.2651 7.2528 7.2607 7.2655 7.3006 7.3019 7.3099 7.3370 7.3485 7.3558 7.3614 7.3822 7.3943 7.4057 7.4183 7.4308 7.4581 7.4704 Bn Bn Bn Bn NAME CCC-80-1 EXPN 1 PRCN 1 Date_ 20110512 Time 9.53 PRBHD 5 mm CPTCI 1H- PULPRG zg TD 32768 SLVENT CDCl3 NS 16 SWH 8370.536 Hz FIDRES 0.255448 Hz AQ 1.9573919 sec RG 2.56 DW 59.733 usec TD0 1 NUC1 1H P1 8.25 usec PL1 4.20 db PL1W 5.82545519 W SF1 600.1336009 MHz SI 16384 SF 600.1300000 MHz LB 0 Hz 10 9 8 7 6 5 4 3 2 1 ppm 2.01 5.01 7.03 4.04 2.05 4.09 3.10 2.01 2.07 2.09 4.08 2.09 2.08 6.01 3.08 3.08 2.07 S14

209.74 210.15 168.81 168.88 127.06 127.08 127.15 127.24 127.36 127.40 127.68 127.96 127.98 128.08 128.12 138.04 138.26 138.29 138.78 43.63 43.82 44.06 48.78 49.03 67.53 67.80 73.09 73.14 74.86 75.12 75.17 75.77 76.79 77.00 77.21 77.40 79.03 79.23 83.48 19.35 19.48 20.86 2 26.16 26.42 NAME CCC-80-1 EXPN 7 PRCN 1 Bn Bn Bn Bn Date_ 20110513 Time 3.38 PRBHD 5 mm CPTCI 1H- PULPRG zgpg30 TD 131072 SLVENT CDCl3 NS 2000 SWH 39062.500 Hz FIDRES 0.298023 Hz AQ 1.6777716 sec RG 2050 DW 12.800 usec D11 0.03000000 sec TD0 2 NUC1 13C P1 10.00 usec PL1-1.82 db PL1W 122.22216797 W SF1 150.9201600 MHz ======== CHANNEL f2 ======== CPDPRG2 waltz16 NUC2 1H PCPD2 90.00 usec PL2 4.20 db PL12 24.96 db PL13 28.13 db PL2W 5.82545519 W PL12W 0.04895001 W PL13W 0.02356839 W SF2 600.1339008 MHz SI 65536 SF 150.9028509 MHz LB 3.00 Hz 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm S15

0.8925 1.0614 1.0698 1.8764 1.9069 3.5958 3.8901 3.8943 3.9064 3.9802 4.1549 4.6770 4.7188 4.7248 4.7383 4.7569 4.7752 4.8122 4.8161 4.8352 4.8452 4.8950 4.9584 4.9951 5.4160 5.4220 7.1175 7.1314 7.1779 7.1830 7.2157 7.2168 7.2226 7.2254 7.2298 7.2341 7.2398 7.2455 7.2482 7.2646 7.2685 7.2774 7.2878 7.3000 7.3129 7.3259 7.3346 7.3379 7.3462 7.3506 7.3583 7.3643 7.3698 7.3726 7.3840 7.3961 7.4580 7.4633 7.4684 7.4738 7.5552 7.6351 7.6370 7.6483 7.6631 7.6651 7.6762 7.6781 7.7194 7.7336 NAME CC-87 EXPN 1 PRCN 1 2-NAP PBB TBDPS Bn Bn N 3 Bn Bn Date_ 20110127 Time 16.52 PRBHD 5 mm CPTCI 1H- PULPRG zg TD 32768 SLVENT CDCl3 NS 20 SWH 8370.536 Hz FIDRES 0.255448 Hz AQ 1.9573919 sec RG 9 DW 59.733 usec TD0 1 NUC1 1H P1 7.75 usec PL1 4.20 db PL1W 5.82545519 W SF1 600.1336009 MHz SI 16384 SF 600.1300353 MHz LB 0 Hz 10 9 8 7 6 5 4 3 2 1 ppm 2.03 8.06 21.07 2.01 1.03 4.05 2.03 1.04 1.02 1.01 2.07 3.06 1.06 1.01 1.03 1.04 4.03 4.06 1.06 1.10 1.03 1.06 2.10 1.04 1.07 3.00 3.03 9.02 S16

209.97 19.31 19.64 21.21 26.29 26.63 26.94 30.90 43.78 44.31 49.12 62.15 63.66 67.99 72.81 73.64 74.49 74.85 75.17 75.32 75.83 76.79 77.00 77.21 78.14 78.80 79.09 80.19 81.54 84.04 98.30 121.73 125.68 125.94 126.10 126.33 127.18 127.24 127.28 127.37 127.48 127.52 127.63 127.65 127.68 127.90 128.12 128.16 128.31 128.39 129.57 129.66 129.68 131.50 132.94 132.99 133.20 133.48 135.42 135.64 135.86 136.80 138.23 138.42 138.60 169.30 NAME CC-87 EXPN 2 PRCN 1 2-NAP p-brbn TBDPS Bn Bn N 3 Bn Bn Date_ 20110128 Time 5.56 PRBHD 5 mm CPTCI 1H- PULPRG zgpg30 TD 131072 SLVENT CDCl3 NS 5100 SWH 39062.500 Hz FIDRES 0.298023 Hz AQ 1.6777716 sec RG 2050 DW 12.800 usec D11 0.03000000 sec TD0 6 NUC1 13C P1 10.00 usec PL1-1.82 db PL1W 122.22216797 W SF1 150.9201600 MHz ======== CHANNEL f2 ======== CPDPRG2 waltz16 NUC2 1H PCPD2 90.00 usec PL2 4.20 db PL12 25.50 db PL13 28.13 db PL2W 5.82545519 W PL12W 0.04319644 W PL13W 0.02356839 W SF2 600.1339008 MHz SI 65536 SF 150.9028193 MHz LB 3.00 Hz 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm S17

1.0720 3.3447 3.3509 3.3620 3.3681 3.4682 3.4722 3.4843 3.4884 3.5204 3.5359 3.7178 3.7216 3.7350 3.7377 3.7511 3.7663 3.8093 3.8253 3.8407 3.8579 3.8633 3.9185 3.9225 3.9264 3.9616 3.9783 4.1319 4.1480 4.7403 4.7604 4.7797 4.7884 4.7967 4.8108 4.8787 4.8974 4.9208 4.9381 4.9764 4.9937 5.0331 5.0505 5.4108 5.4170 7.1728 7.1866 7.2370 7.2400 7.2533 7.2663 7.3125 7.3194 7.3282 7.3354 7.3688 7.3900 7.4037 7.4204 7.4922 7.4975 7.5025 7.5079 7.5809 7.6408 7.6522 7.6757 7.6870 7.7381 7.7523 NAME CCC-89 EXPN 1 PRCN 1 2-NAP PBB TBDPS N 3 Bn Bn Bn Bn H Date_ 20110503 Time 9.46 PRBHD 5 mm CPTCI 1H- PULPRG zg TD 32768 SLVENT CDCl3 NS 20 SWH 8370.536 Hz FIDRES 0.255448 Hz AQ 1.9573919 sec RG 7.12 DW 59.733 usec TD0 1 NUC1 1H P1 7.85 usec PL1 4.20 db PL1W 5.82545519 W SF1 600.1336009 MHz SI 16384 SF 600.1300287 MHz LB 0 Hz 10 9 8 7 6 5 4 3 2 1 ppm 2.01 29.09 2.01 4.04 2.06 1.01 5.07 5.09 2.07 2.10 2.08 4.06 1.02 1.10 9.08 S18

62.60 63.46 72.41 72.96 74.49 74.96 75.07 75.42 75.50 75.67 76.79 77.00 77.21 78.43 79.50 80.09 81.76 81.89 84.01 98.80 121.80 125.58 125.98 126.17 126.26 127.51 127.61 127.71 127.77 127.82 127.86 128.05 128.15 128.40 128.49 129.61 129.73 131.54 132.93 132.99 133.16 133.24 135.28 135.58 135.79 136.72 138.41 138.45 138.62 26.85 19.24 NAME CCC-89 EXPN 7 PRCN 1 2-NAP PBB TBDPS N 3 Bn Bn Bn Bn H Date_ 20110503 Time 17.53 PRBHD 5 mm CPTCI 1H- PULPRG zgpg30 TD 131072 SLVENT CDCl3 NS 3000 SWH 39062.500 Hz FIDRES 0.298023 Hz AQ 1.6777716 sec RG 2050 DW 12.800 usec D11 0.03000000 sec TD0 3 NUC1 13C P1 10.00 usec PL1-1.82 db PL1W 122.22216797 W SF1 150.9201600 MHz ======== CHANNEL f2 ======== CPDPRG2 waltz16 NUC2 1H PCPD2 90.00 usec PL2 4.20 db PL12 25.39 db PL13 28.13 db PL2W 5.82545519 W PL12W 0.04431837 W PL13W 0.02356839 W SF2 600.1339008 MHz SI 65536 SF 150.9028229 MHz LB 3.00 Hz 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm S19

05 2.2779 3.4236 3.4390 3.4414 3.4478 3.4543 3.4588 3.4648 3.4778 3.4817 3.4942 3.4978 3.6590 3.6625 3.6756 3.6791 3.7957 3.8018 3.8060 3.8090 3.8259 3.8420 3.8622 3.8780 3.8938 4.0272 4.0431 4.0591 4.0746 4.1416 4.1452 4.1486 4.7425 4.7614 4.7765 4.7816 4.7865 4.7983 4.8040 4.8098 4.8219 4.8288 4.8319 4.8502 4.8655 4.8833 4.9092 4.9281 4.9997 5.0183 5.1128 5.1188 7.2909 7.3431 7.3478 7.3801 7.3937 7.5102 7.5258 7.5624 7.6273 7.6386 7.6672 7.6784 7.7555 7.7696 7.8625 7.8726 NAME CCC-71 EXPN 1 PRCN 1 2-NAP p-brbn TBDPS Bn H N 3 Bn Bn Bn Date_ 20110801 Time 10.59 PRBHD 5 mm CPDCH 13C PULPRG zg30 TD 32768 SLVENT CDCl3 NS 30 SWH 8389.262 Hz FIDRES 0.256020 Hz AQ 1.9530228 sec RG 36 DW 59.600 usec TD0 1 NUC1 1H P1 7.70 usec PL1 4.20 db PL1W 5.72995567 W SF1 600.1536010 MHz SI 16384 SF 600.1500283 MHz LB 0 Hz 9 8 7 6 5 4 3 2 1 0 ppm 2.06 1.05 1 9.07 6.03 2.07 2.03 2.03 2.09 1.12 1.02 2.05 1.06 3.09 1.01 3.06 1.21 2.05 2.10 2.02 2.02 2.05 1.06 9.09 S20

62.37 63.39 71.87 72.45 74.27 74.54 74.68 74.77 75.01 75.32 75.61 76.03 76.79 77.00 77.21 78.43 80.13 80.65 81.50 83.75 93.67 121.78 125.65 125.91 126.07 126.11 127.38 127.51 127.60 127.64 127.68 127.73 127.85 128.01 128.06 128.15 128.29 128.31 128.42 128.46 128.53 129.66 131.51 132.88 133.06 133.15 133.37 135.54 135.81 136.70 138.14 138.42 138.50 26.88 19.31 NAME CCC-71 EXPN 2 PRCN 1 2-NAP p-brbn TBDPS Bn H N 3 Bn Bn Bn Date_ 20110801 Time 11.01 PRBHD 5 mm CPDCH 13C PULPRG zgpg30 TD 131072 SLVENT CDCl3 NS 55 SWH 39062.500 Hz FIDRES 0.298023 Hz AQ 1.6777716 sec RG 3640 DW 12.800 usec DE 6.00 usec D11 0.03000000 sec TD0 1 NUC1 13C P1 10.50 usec PL1 2.80 db PL1W 49.17097855 W SF1 150.9251891 MHz ======== CHANNEL f2 ======== CPDPRG2 waltz16 NUC2 1H PCPD2 80.00 usec PL2 0.33 db PL12 17.18 db PL13 20.18 db PL2W 13.96854782 W PL12W 0.28850359 W PL13W 0.14459431 W SF2 600.1539010 MHz SI 65536 SF 150.9078540 MHz LB 2.00 Hz 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm S21

3.3639 3.3695 3.3811 3.3867 3.6202 3.6356 3.6826 3.6950 3.6988 3.7393 3.7545 3.8010 3.8068 3.8421 3.8592 3.8809 3.8831 3.8899 3.9054 3.9430 3.9588 4.0485 4.0653 4.0949 4.0985 4.2695 4.8791 4.8913 4.9120 4.9310 4.9903 4.9939 5.0027 5.0085 5.0223 5.0465 5.0656 5.1032 5.1171 5.5092 5.5149 7.2399 7.2537 7.3792 7.3872 7.3908 7.3989 7.4130 7.4163 7.4300 7.4418 7.4640 7.4682 7.4778 7.4811 7.5344 7.5462 7.5772 7.5828 7.5894 7.5913 7.7869 7.8712 7.8791 7.8858 7.9000 7.9146 7.9169 7.9237 7.9330 2-NAP PBB H N 3 Bn Bn Bn Bn H NAME CCC-141 EXPN 1 PRCN 1 Date_ 20110512 Time 10.11 PRBHD 5 mm CPTCI 1H- PULPRG zg TD 32768 SLVENT CDCl3 NS 16 SWH 8370.536 Hz FIDRES 0.255448 Hz AQ 1.9573919 sec RG 3.2 DW 59.733 usec TD0 1 NUC1 1H P1 7.70 usec PL1 4.20 db PL1W 5.82545519 W SF1 600.1336009 MHz SI 16384 SF 600.1300001 MHz LB 0 Hz 10 9 8 7 6 5 4 3 2 1 ppm 2.02 14.06 7.07 2.09 2.04 1.05 3.08 1.06 1.04 1.06 3.04 2.05 1.02 3.08 2.06 4.00 2.08 2.06 S22

61.17 63.21 72.20 72.37 74.26 74.92 74.94 75.26 75.39 75.61 76.79 77.00 77.04 77.21 77.94 79.52 79.73 81.67 81.75 83.94 98.75 121.68 125.49 126.00 126.19 126.32 127.34 127.39 127.55 127.63 127.74 127.78 127.93 128.18 128.28 128.31 128.39 128.43 129.44 131.42 132.88 133.08 135.08 136.60 138.22 138.32 138.35 138.52 NAME CCC-141 EXPN 7 PRCN 1 2-NAP PBB H N 3 Bn Bn Bn Bn H Date_ 20110512 Time 17.16 PRBHD 5 mm CPTCI 1H- PULPRG zgpg30 TD 131072 SLVENT CDCl3 NS 1600 SWH 39062.500 Hz FIDRES 0.298023 Hz AQ 1.6777716 sec RG 2050 DW 12.800 usec D11 0.03000000 sec TD0 1 NUC1 13C P1 10.00 usec PL1-1.82 db PL1W 122.22216797 W SF1 150.9201600 MHz ======== CHANNEL f2 ======== CPDPRG2 waltz16 NUC2 1H PCPD2 90.00 usec PL2 4.20 db PL12 25.56 db PL13 28.13 db PL2W 5.82545519 W PL12W 0.04264094 W PL13W 0.02356839 W SF2 600.1339008 MHz SI 65536 SF 150.9028455 MHz LB 3.00 Hz 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm S23

3.2460 3.2616 3.2772 3.3014 3.3075 3.3192 3.3253 3.4318 3.4473 3.4631 3.4860 3.4905 3.5028 3.5071 3.5519 3.5678 3.5842 3.6439 3.6482 3.6607 3.6652 3.7131 3.7180 3.7331 3.7405 3.7502 3.7831 3.7862 3.7955 3.7997 3.8030 3.8119 3.8323 3.8655 3.8808 3.8984 4.1489 4.1529 4.1573 4.7002 5.3702 5.3763 H NAME CCC-101 EXPN 1 PRCN 1 Date_ 20110505 Time 16.43 PRBHD 5 mm CPTCI 1H- PULPRG zg TD 32768 SLVENT D2 NS 8 SWH 9615.385 Hz FIDRES 0.293438 Hz AQ 1.7039860 sec RG 1 DW 52.000 usec TE 297.9 K TD0 1 NUC1 1H P1 13.29 usec PL1 3.10 db PL1W 8.25510406 W SF1 600.1428505 MHz SI 32768 SF 600.1399978 MHz LB 0.30 Hz 10 9 8 7 6 5 4 3 2 1 ppm 1.01 1.07 1.07 1.07 1.07 2.08 2.08 H H HCl. NH 2 H H H H H S24

97.35 60.31 69.46 69.66 70.98 71.73 71.94 72.03 72.75 74.15 78.95 54.28 H H NAME CCC-101 EXPN 7 PRCN 1 H HCl. NH 2 H H H H H Date_ 20110429 Time 15.31 PRBHD 5 mm CPTCI 1H- PULPRG zgpg30 TD 131072 SLVENT D2 NS 2000 SWH 39062.500 Hz FIDRES 0.298023 Hz AQ 1.6777716 sec RG 2050 DW 12.800 usec D11 0.03000000 sec TD0 2 NUC1 13C P1 10.00 usec PL1-1.82 db PL1W 122.22216797 W SF1 150.9201600 MHz ======== CHANNEL f2 ======== CPDPRG2 waltz16 NUC2 1H PCPD2 90.00 usec PL2 4.00 db PL12 25.13 db PL13 28.13 db PL2W 6.09999990 W PL12W 0.04702512 W PL13W 0.02356839 W SF2 600.1339008 MHz SI 65536 SF 150.9028090 MHz LB 3.00 Hz 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm S25

1.4168 2.3753 3.0914 3.1057 3.1151 3.1294 3.2392 3.2549 3.2706 3.3785 3.3864 3.4024 3.4102 3.4441 3.4599 3.4757 3.4893 3.4938 3.5059 3.5103 3.5593 3.5629 3.5762 3.5803 3.5883 3.6043 3.6204 3.7514 3.7627 3.7670 3.7718 3.8064 3.8087 3.8239 3.8471 3.8651 3.9241 3.9297 3.9419 3.9475 4.1768 4.3013 4.3093 4.3150 4.3229 4.8003 5.1209 5.1282 H H H HN AcS NHBoc H H H H H NAME CCC-197-30 EXPN 1 PRCN 1 Date_ 20110812 Time 16.46 PRBHD 5 mm CPDCH 13C PULPRG zg30 TD 32768 SLVENT D2 NS 18 SWH 8389.262 Hz FIDRES 0.256020 Hz AQ 1.9530228 sec RG 36 DW 59.600 usec TD0 1 NUC1 1H P1 10.00 usec PL1-0.80 db PL1W 18.11971092 W SF1 600.1536010 MHz SI 16384 SF 600.1499433 MHz LB 0 Hz 9 8 7 6 5 4 3 2 1 0 ppm 1.06 1.01 1.06 1.03 1.04 1.05 2.11 3.07 1.04 3.04 9.02 S26

199.99 172.56 157.42 99.10 53.96 54.13 60.52 70.00 70.71 71.03 71.69 72.05 72.49 74.20 78.97 81.86 27.53 29.83 30.72 NAME CCC-208-P-All EXPN 2 PRCN 1 H H H HN AcS NHBoc H H H H H Date_ 20110818 Time 23.28 PRBHD 5 mm CPDCH 13C PULPRG zgpg30 TD 131072 SLVENT D2 NS 4800 SWH 39062.500 Hz FIDRES 0.298023 Hz AQ 1.6777716 sec RG 3640 DW 12.800 usec D11 0.03000000 sec TD0 1 NUC1 13C P1 10.50 usec PL1 2.80 db PL1W 49.17097855 W SF1 150.9251891 MHz ======== CHANNEL f2 ======== CPDPRG2 waltz16 NUC2 1H PCPD2 80.00 usec PL2 0.33 db PL12 16.95 db PL13 20.18 db PL2W 13.96854782 W PL12W 0.30419436 W PL13W 0.14459431 W SF2 600.1539010 MHz SI 65536 SF 150.9078380 MHz LB 2.00 Hz 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm S27

2.0523 2.8663 2.8774 2.8898 2.9016 2.9051 2.9144 2.9292 2.9379 3.2626 3.2779 3.2937 3.4446 3.4606 3.4764 3.5005 3.5050 3.5169 3.5215 3.5619 3.5665 3.5786 3.5833 3.6015 3.6173 3.6335 3.7528 3.7616 3.7695 3.7819 3.7854 3.7993 3.8147 3.8335 3.8486 3.8666 3.9607 3.9668 3.9786 4.1742 4.1784 4.5013 4.5112 4.5213 5.1190 5.1250 NAME CCC-212 EXPN 1 PRCN 1 H Date_ 20110831 Time 17.32 PRBHD 5 mm CPDCH 13C PULPRG zg30 TD 32768 SLVENT D2 NS 65 SWH 8389.262 Hz FIDRES 0.256020 Hz AQ 1.9530228 sec RG 36 DW 59.600 usec TD0 1 H H H H H H H HN HS NHAc NUC1 1H P1 10.00 usec PL1-0.80 db PL1W 18.11971092 W SF1 600.1536010 MHz S28 SI 16384 SF 600.1499427 MHz LB 0 Hz - 9 8 7 6 5 4 3 2 1 0 ppm 3.08 2.00 1.11 1.03 1.12 3.16 2.07 1.03 1.01

172.03 174.38 99.18 53.85 55.69 60.52 70.03 70.78 71.02 71.69 72.02 72.05 72.51 74.19 79.00 25.63 21.72 NAME CCC-212-P-All EXPN 2 PRCN 1 H H H HN HS NHAc H H H H H Date_ 20110901 Time 22.11 PRBHD 5 mm CPDCH 13C PULPRG zgpg30 TD 131072 SLVENT D2 NS 5352 SWH 39062.500 Hz FIDRES 0.298023 Hz AQ 1.6777716 sec RG 3640 DW 12.800 usec D11 0.03000000 sec TD0 1 NUC1 13C P1 10.50 usec PL1 2.80 db PL1W 49.17097855 W SF1 150.9251891 MHz ======== CHANNEL f2 ======== CPDPRG2 waltz16 NUC2 1H PCPD2 80.00 usec PL2 0.33 db PL12 16.95 db PL13 20.18 db PL2W 13.96854782 W PL12W 0.30419436 W PL13W 0.14459431 W SF2 600.1524006 MHz SI 65536 SF 150.9078380 MHz LB 2.00 Hz 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm S29