Ingrid 't Hart

86 Chapter 4 4 4.83 (1H, d, J = 12.5 Hz, CH H ), 4.72 (1H, d, J = 10.1 Hz, H-1), 4.65 (1H, d, J = 12.5 Hz, CH H ), 4.60 (2H, s, CH 2 ), 4.22 (1H, d, J = 2.8 Hz, H-4), 3.89 – 3.78 (2H, m, H-6a,b), 3.73 – 3.66 (2H, m, H-3; H-5). 13 C NMR (151 MHz, CDCl 3 ) δ 165.4 (C=O), 138.0, 134.4, 133.3, 133.2, 133.0, 132.2, 129.9, 128.8, 128.5, 128.4, 128.4, 127.9, 127.8, 127.7, 127.7, 126.9, 126.2, 126.1, 125.8, 86.7 (C-1), 79.1 (C-3), 77.5 (C-5), 73.8 (CH 2 ), 71.3 (CH 2 ), 69.6 (C-2), 69.3 (C- 6), 66.3 (C-4). ESI HRMS (m/z): [M + NH] + calcd for C 37 H 34 O 6 S; 624.2430 found 624.2420. Phenyl 2- O -benzoyl-6- O -benzyl-4- O -levulenoyl-3- O -(2-naphthyl)methyl-1-thio-β-D- galactopyranoside (28). A mixture of levulinic acid (0.21 mL, 2.0 mmol), EDCHCl (391 mg, 2.0 mmol), NEt 3 (0.28 mL, 2.0 mmol) and DMAP (30 mg, 0.24 mmol) was s�rred in DCM (3 mL) for 1 h. This mixture was added to compound 27 (495 mg, 0.82 mmol) in DCM (2 mL). The reac�on mixture was s�rred overnight and a fresh LevOH/EDC mix was made and a�er s�rring for an addi�onal 1 h, added to the reac�on mixture. This was repeated once more and then the mixture was washed with H 2 O, brine, extracted with DCM and the organic layer was dried (Na 2 SO 4 ), filtered and and the filtrate concentrated in vacuo . The obtained residue was purified by silica column chromatography using Toluene:Acetone (1:0 to 100:10 v/v) as the eluent to afford compound 28 (294 mg, 51 %) and star�ng material 27 (257 mg). The star�ng material was submi�ed for Lev protec�on as described above to obtain more compound 28 (140mg, 47%). (Total overall yield: 434mg, 75%). 1 HNMR (600MHz, CDCl 3 ) δ 7.95 (2H, d, J = 7.9 Hz, H-Ar), 7.70 (1H, d, J = 8.0 Hz, H-Ar), 7.64 – 7.53 (2H, m, J = 19.5, 12.1 Hz, H-Ar), 7.51 (1H, d, J = 8.0 Hz, H-Ar), 7.47 – 7.12 (16H, m, H-Ar), 5.73 (1H, d, J = 3.0 Hz, H-4), 5.42 (1H, t, J = 9.8 Hz, H-2), 4.79 – 4.72 (2H, m, CH H ; H-1), 4.57 – 4.51 (3H, m, CH H ; CH 2 ), 3.82 (1H, t, J = 6.3 Hz, H-5), 3.73 – 3.68 (2H, m, H-6a; H-3), 3.61 (1H, dd, J = 9.5, 6.9 Hz, H-6b), 2.85 – 2.56 (4H, m, 2x CH 2 , Lev), 2.17 (3H, s, CH 3 , Lev). 13 C NMR (151 MHz, CDCl 3 ) δ 206.4 (H 3 C-C =O, Lev), 172.1 (O- C =O, Lev), 165.3 (C=O, Bz), 134.6, 133.2, 132.4, 130.0, 128.8, 128.5, 128.4, 128.2, 127.8, 127.6, 126.9, 126.0, 125.9, 86.8 (C-1), 77.1 (C-3), 76.3 (C-5), 73.8 (CH 2 ), 70.8 (CH 2 ), 69.5 (C-2), 68.2 (C-6), 66.4 (C-4), 38.1 (CH 2 , Lev), 29.9 (CH 3 , Lev), 28.1 (CH 2 , Lev). ESI HRMS (m/z): [M + NH] + calcd for C 42 H 40 O 8 S; 722.2788 found 722.2799. 2,2,2-Trichloroace�midate 2- O -benzoyl-6- O -benzyl-4- O -levulenoyl-3- O -(2-naphthyl) methyl-α/β-D-galactopyranoside (7). N -iodosuccinimide (255 mg, 1.13 mmol) and TFA (87 µL, 1.13 mmol) were added to a cooled (0 °C) mixture of compound 28 (400 mg, 0.57 mmol) in DCM (10 mL). A�er 2 h the mixture was washed with sat. aq. NaHCO 3 , extracted with DCM, washed with 5 % NaS 2 O 3 , dried (Na 2 SO 4 ), filtered and concentrated in vacuo . The obtained residue was purified by silica column chromatography using Hexane:EtOAc (1:0 to 1:1 v/v) as the eluent to afford the free reducing intermediate (236 mg, 68 %). 2,2,2-trichloroacetonitrile (192 µL, 1.92 mmol) and DBU (11 µL, 0.077 mmol) were added to this intermediate (235 mg, 0.38 mmol) in DCM (10 mL) at 0 °C. A�er 1 h the mixture was concentrated in vacuo and the residue was purified by silica column chromatography using Hexane (1% Et 3 N):EtOAc (1:0 to 1:1 v/v) as the eluent to afford compound 7 as an α/β mixture (230 mg, 79 %). 1 H NMR (α/β mixture 2/1) (600 MHz, CDCl 3 ) δ 8.56 (0.5H, s, N H , β), 8.40 (1H, s, N H , α), 7.90 – 7.83 (3H, m, H-Ar), 7.79 – 7.27 (24H, m, H-Ar), 7.20 (0.5H, dd, J = 8.4, 1.6 Hz, H-Ar), 6.63 (1H, d, J = 3.5 Hz, H-1, α), 5.90 – 5.86 (1H, m, H-4, α), 5.83 (0.5H, d, J = 8.4 Hz, H-1, β), 5.79 (0.5H, dd, J = 3.3, 1.0 Hz, H-4, β), 5.66 (0.5H, O OBn LevO NapO OBz SPh O OBn LevO NapO OBz O CCl 3 NH