Ingrid 't Hart

84 Chapter 4 4 Scheme S1. Chemical glycosyla�on of GlcNAc-II donor 8 and GalNAc-I acceptor 9 and forma�on of disaccharide acceptor 11 . Reagents and condi�ons: (a) TMSOTf, CH 2 Cl 2 , -70 °C; (b) NaOMe, CH 2 Cl 2 / MeOH. N -(Benzyl)-benzyloxycarbonyl-5-aminopentyl 4- O -acetyl-3,6-di- O -benzyl-2-deoxy- 2-phthalimido-β-D-glucopyranosyl-(1→3)-2-azido-4,6- O -benzylidene-2-deoxy-α- D-galactopyranoside (13). A mixture of acceptor 9 (188 mg, 0.31 mmol) and donor 8 (316 mg, 0.47 mmol) and 4 Å molecular sieves was s�rred in DCM (3.6 mL) for 2 h. The reac�on mixture was cooled to -70 °C and a solu�on of TMSOTf (11 µL, 0.06 mmol) in DCM (100 µL) was added. A�er 40 min the reac�on was quenched with Et 3 N, filtered over a pad of Celite and concentrated in vacuo . The obtained residue was purified by silica column chromatography using Toluene:EtOAc (1:0 to 8.5:1.5 v/v) as the eluent to afford compound 13 (251 mg, 72 %). 1 H NMR (600 MHz, CDCl 3 ) δ 7.80 – 7.57 (4H, m, Ar-H), 7.47 (2H, d, J = 7.6 Hz, Ar-H), 7.42 – 7.21 (18H, m, Ar-H), 6.95 (5H, ddd, J = 25.0, 21.7, 7.3 Hz, Ar-H), 5.43 (1H, d, J = 8.4 Hz, H-1, GlcNAc-II), 5.39 (1H, s, C H -C 6 H 5 ), 5.17 (2H, d, J = 11.8 Hz, CH 2 ), 5.09 (1H, t, J = 9.4 Hz, H-4, GlcNac-II), 4.79 (1H, d, J = 14.8 Hz, H-1, GalNAc-I), 4.60 (1H, d, J = 12.0 Hz, C H H, Bn), 4.55 – 4.31 (8H, m, C H H, Bn; CH 2 ; H-3, GlcNAc-II; CH H , Bn; H-4, GalNAc-I; H-2, GlcNAc-II; CH H , Bn), 4.04 (1H, d, J = 11.6 Hz, H-6a, GalNAc-I), 3.95 (1H, d, J = 7.8 Hz, H-3, GalNAc-I), 3.84 (1H, dd, J = 12.1, 5.0 Hz, H-5, GlcNAc-II), 3.67 – 3.11 (9H, m, H-6, GlcNAc-II; H-6b, GalNAc-I; H-2, GalNAc-I; C H H, pentyl; H-5, GalNAc-I; CH H , pentyl; CH 2 , pentyl), 1.99 (3H, s, CH 3 , OAc), 1.49 (4H, d, J = 33.8 Hz, 2x CH 2 , pentyl), 1.23 (2H, d, J = 37.0 Hz, CH 2 , pentyl). 13 C NMR (151 MHz, CDCl 3 ) δ 169.8 (C, OAc), 138.0 (C=O, Cbz), 137.8 (C, NPhth), 137.6 (C, NPhth), 133.7, 131.7, 129.1, 128.7, 128.6, 128.5, 128.3, 128.2, 128.1, 128.0, 127.9, 127.9, 127.8, 127.5, 127.2, 126.1, 123.3, 100.4 ( C H-C 6 H 5 ), 99.8 (C-1, GlcNAc-II), 98.4 (C-1, GalNAc-I), 77.0 (C-3, GlcNAc-II), 76.3 (C-3, GalNAc-I), 75.3 (C-4, GalNAc-I), 73.9 (CH 2 , Bn), 73.6 (CH 2 , Bn), 73.3 (C-5, GlcNAc-II), 72.3 (C-4, GlcNAc-II), 70.3 (C-6, GlcNAc-II), 68.9 (C-6, GalNAc-I), 68.2 (CH 2 , pentyl), 67.2 (CH 2 ), 63.0 (C-5, GalNAc-I), 58.2 (C-2, GalNAc-I), 55.4 (C-2, GlcNAc-II), 50.3 (CH 2 ), 47.1 (CH 2 , pentyl), 46.11 (CH 2 , pentyl), 29.0 (CH 2 , pentyl), 27.9 (CH 2 , pentyl), 27.4 (CH 2 , pentyl), 23.2 (CH 2 , pentyl), 20.9 ( C H 3 , OAc). ESI HRMS (m/z): [M + Na] + calcd for C 63 H 65 N 5 O 14 ; 1138.4426 found 1138.4455. N -(Benzyl)-benzyloxycarbonyl-5-aminopentyl 3,6-di- O -benzyl-2-deoxy-2-phthalimido- β-D-glucopyranosyl-(1→3)-2-azido-4,6- O -benzylidene-2-deoxy-α-D-galactopyranoside (11). Freshly prepared NaOMe (2.5 mL) was added to a s�rring solu�on of compound 13 (243 mg, 0.22 mmol) in DCM/MeOH (2.5/5 mL). A�er 1.5 h, Amberlite H + resin was added and the reac�on mixture was filtered and concentrated in vacuo to afford compound 11 (226mg, 97 %). 1 H NMR (600MHz, CDCl 3 ) δ 7.84 – 7.55 (4H, m, H-Ar), 7.49 – 7.42 (2H, m, O NPht BnO AcO BnO O NPht BnO AcO BnO O CCl 3 NH a + b O O O HO N 3 O NBnCbz Ph 9 n = 5 O O O O N 3 O NBnCbz Ph n = 5 O NPht BnO HO BnO O O O O N 3 O NBnCbz Ph n = 5 8 11 , 97% 13 , 72% O O O O N 3 O Ph NBnCbz O NPht BnO AcO BnO O O O O N 3 O Ph NBnCbz O NPht BnO HO BnO