Ingrid 't Hart

43 Chemoenzyma�c synthesis of DSGb5 2 Para-methoxyphenyl2-O-benzyl-3-O-(2-naphthyl)methyl-4,6-O-di-tert-butylsilanediyl- β-D-galactopyranosyl-(1 → 4)-2,3,6-tri-O-benzyl-β-D-galactopyranosyl-(1 → 4)-2,3,6-tri- O-benzyl-β-D-gluco-pyranoside (15a). A mixture of acceptor 12a (1.54 g, 1.56 mmol), donor 11 (1.20 g, 1.87 mmol) and 4 Å molecular sieves was s�rred in DCM (15 mL) for 1 h. The reac�on mixture was cooled to -30°C and N-iodosuccinimide (700 mg, 3.1 mmol) and triflic acid (14 µL, 0.16 mmol) were added. A�er 35 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 gel chromatography using Toluene:EtOAc (1:0 to 20:1 v/v) as the eluent to afford compound 15a (2.13 g, 90 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.84 – 7.64 (4H, m, Ar-H), 7.49 – 7.39 (4H, m, Ar-H), 7.36 – 7.13 (34H, m, Ar-H), 7.01 (2H, d, J = 9.0 Hz, OMP), 6.78 (2H, d, J = 9.0 Hz, OMP), 5.12 – 5.07 (1H, d, J = 11.3 Hz, CHH), 5.01 – 4.92 (2H, m, H-1, Gal-III; CHH), 4.85 (1H, d, J = 7.3 Hz, H-1, Glc-I), 4.83– 4.64 (8H, m, 4x CH 2 ), 4.62 – 4.52 (2H, m, 2x CHH), 4.52 – 4.41 (3H, m, CHH; H-1, Gal-II; H-4, Gal-III), 4.40 – 4.24 (3H, m, CH 2 ; CHH), 4.17 – 3.87 (6H, m, H-6a, Gal-II; H-4, Glc-I; H-2, Gal-III, H-5, Gal-II; H-4, Gal-II; H-3, Gal-III) 3.83 – 3.78 (4H, m, H-6, Glc-I; H-6, Gal-III), 3.76 (3H, s, CH 3 , OMP), 3.70 – 3.60 (2H, m, H-2, Glc-I; H-5, Gal-III), 3.59 – 3.43 (3H, m, H-2, Gal-II; H-6b, Gal-II; H-5, Glc-I), 3.35 (1H, dd, J = 8.1, 5.5 Hz, H-3, Glc-I), 3.29 (1H, dd, J = 10.0, 2.7 Hz, H-3, Gal-II), 1.01 (9H, s, t-Bu), 0.99 (9H, s, t-Bu). 13 C NMR (101 MHz, CDCl 3 ) δ 155.2 (C, OMP), 151.6 (C, OMP), 139.2 (C, Ar), 138.7 (C, Ar), 138.5 (C, Ar), 138.4 (C, Ar), 138.3 (C, Ar), 138.2 (C, Ar), 136.7 (C, Ar), 133.2, 132.9, 129.0, 128.5, 128.4, 128.4, 128.3, 128.2, 128.2, 128.2, 128.1, 127.9, 127.8, 127.7, 127.7, 127.6, 127.6, 127.6, 127.5, 127.4, 127.4, 127.4, 127.4, 126.0, 125.9, 125.9, 125.7, 118.5 (2x CH, OMP), 114.5 (2x CH, OMP), 103.1 (C-1, Glc-I), 102.7 (C-1, Gal-II), 100.2 (C-1, Gal-III), 82.5 (C-5, Gal-III), 81.5 (C-2, Glc-I), 81.1 (C-3, Gal-II), 79.1 (C-2, Gal-II), 78.0 (C-3, Gal-III), 77.2 (C-5, Gal-II), 75.3 (C-5, Glc-I), 75.2, 75.1, 74.9, 74.3 (C-2, Gal-III), 73.7, 73.5 (C-4, Glc-I), 73.4 (C-3, Glc-I), 73.2, 73.1, 72.2, 71.2 (C-4, Gal-III), 70.6, 68.4 (C-6, Glc-I), 67.7 (C-6, Gal-II), 67.5 (C-4, Gal-II), 67.1 (C-6, Gal-III), 55.6 (CH 3, OMP), 27.7 (CH 3 , t-Bu), 27.3 (CH 3 , t-Bu), 23.3 (C, t-Bu), 20.7 (C, t-Bu). ESI HRMS (m/z): [M + NH 4 ] + calcd for C 93 H 104 O 17 Si, 1538.7381; found 1538.7403. [α] 25/589 = 357.2° (C = 0.1; CHCl 3 ). Para-methoxyphenyl 2-O-benzyl-4,6-O-di-tert-butylsilanediyl-β-D-galactopyranosyl- (1 → 4)-2,3,6-tri-O-benzyl-β-D-galactopyranosyl-(1 → 4)-2,3,6-tri-O-benzyl-β-D-glucopyr- anoside (8a). DDQ (377 mg, 1.7 mmol) was added to a s�rring solu�on of compound 15a (2.1 g, 1.4 mmol) in DCM (120 mL) and PBS buffer (pH 7.4, 5 mL) and the reac�on mixture was kept in darkness. A�er 3 h, the mixture was diluted with DCM, washed with sat. aq. NaHCO 3 (2 x), H 2 O, dried (Na 2 SO 4 ), filtered and concentrated in vacuo . Purifica�on by silica column chromatography using Toluene:EtOAc (1:0 to 4:1 v/v) as the eluent provided compound 8a (987 mg, 52 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.42 (2H, d, J = 7.0 O O OBn BnO OBn OMP O OBn BnO BnO O O O NapO O BnO Si O O OBn BnO OBn OMP O OBn BnO BnO O O O HO O BnO Si