Ingrid 't Hart

65 Synthesis of globo-series glycolipids 3 (2S,3R,4E)-2-azido-3-O-benzoyloxy-octadec-4-enyl 2,3-di- O -benzyl-4,6- O -benzylidene- β-D-galactopyranosyl-(1→4)-2,3,6-tri- O -benzyl-β-D-glucopyranoside (6). A mixture of acceptor 5 (447 mg, 1.0 mmol), donor 4 (1.60 g, 1.6 mmol) and 4 Å molecular sieves was s�rred in DCM for 3 h. The mixture was cooled to -50 °C and BF 3 OEt 2 (38 µL, 0.3 mmol) was added. The mixture was allowed to warm to -20 °C over 2 h. The reac�on mixture was quenched with Et 3 N, filtered over Celite and concentrated in vacuo . The obtained residue was purified by silica column chromatography using Hexane:EtOAc (1:0 to 7:3 v/v) as the eluent to afford compound 6 (962 mg, 71 %, only β anomer). 1 H NMR (400 MHz, CDCl 3 ) δ 8.06 (2H, d, J = 7.3 Hz, H-Ar), 7.61 – 7.09 (33H, m, H-Ar), 5.96 – 5.80 (1H, m, CH=C H -CH 2 ), 5.71 – 5.61 (1H, m, C H OBz), 5.61 – 5.48 (1H, m, CHOBz-C H =CH), 5.45 (1H, s, C H -C 6 H 5 ), 5.19 (1H, d, J = 10.6 Hz, CH H ), 5.00 – 4.65 (7H, m), 4.52 (1H, d, J = 12.1 Hz, CH H ), 4.46 (1H, d, J = 7.8 Hz, H-1, Gal-II), 4.39 (1H, d, J = 7.6 Hz, H-1, Glc-I), 4.30 (1H, d, J = 12.1 Hz, CH H ), 4.19 (1H, d, J = 12.3 Hz, CH H ), 4.06 – 3.54 (10H, m), 3.47 (1H, t, J = 8.3 Hz), 3.38 (2H, dd, J = 17.4, 7.4 Hz), 2.94 (1H, s), 2.02 (2H, d, J = 6.8 Hz, CH=CH-C H 2 ), 1.44 – 1.13 (22H, m, 11 x CH 2 ), 0.87 (3H, t, J = 6.6 Hz, CH 3 , Sph). ESI HRMS ( m/z ): [M + NH 4 ] + calcd for C79H93N3O13; 1309.7047 found 1309.7098. (2S,3R,4E)-2-azido-3-O-benzoyloxy-octadec-4-enyl 2,3-di- O -benzyl-6- O -benzyl-β-D- galactopyranosyl-(1→4)-2,3,6-tri- O -benzyl-β-D-glucopyranoside (7). Compound 6 (1.0 g, 0.77 mmol) was s�rred in DCM (7 mL) with 4 Å molecular sieves for 2.5 h. The mixture was cooled to -70 °C and Et 3 SiH (616 µL, 3.87 mmol) and TfOH (137 µL, 1.55 mmol) were added. A�er 1 h the same amounts of Et 3 SiH and TfOH were added. The mixture was allowed to warm to -40 °C a�er which it was quenched by addi�on of Et 3 N. The crude was filtered over Celite, concentrated in vacuo and purified by silica column chromatography using Hexane:EtOAc (1:0 to 7:3 v/v) as the eluent to afford compound 7 (719 mg, 72 %). 1 H NMR (400 MHz, CDCl 3 ) δ 8.06 (2H, d, J = 7.3 Hz, H-Ar), 7.61 – 7.11 (32H, m, H-Ar), 5.92 – 5.83 (1H, m, CH=C H -CH 2 ), 5.66 (1H, dd, J = 8.0, 3.8 Hz, C H OBz), 5.55 (1H, dd, J = 15.4, 7.9 Hz, CHOBz- C H =CH), 4.99 (1H, d, J = 10.8 Hz, CH H ), 4.88 (1H, d, J = 11.1 Hz, CH H ), 4.80 – 4.62 (6H, m), 4.52 (1H, d, J = 12.2 Hz, CH H ), 4.47 – 4.31 (5H, m, H-1, Gal-II; H-1, Glc-I), 4.04 – 3.90 (4H, m, H-4, Gal-II; C H N 3 ), 3.78 (1H, dd, J = 11.0, 4.2 Hz), 3.71 – 3.53 (5H, m, H-2, Gal-II), 3.49 – 3.29 (5H, m, H-2, Glc-I; H-3, Gal-II), 2.43 (1H, d, J = 2.4 Hz, O H ), 2.04 – 1.97 (2H, m, CH=CH-CH 2 , Sph), 1.44 – 1.17 (22H, m, 11 x CH 2 , Sph), 0.87 (3H, t, J = 6.9 Hz, CH 3 , Sph). Phenyl 2- O -benzyl-3- O -(2-naphthyl)methyl-4,6- O -di- tert- butylsilanediyl-1-thio-β-D- galactopyranoside (8a ) Compound 8a was synthesized as described before (chapter 2: compound 11). 28 O O OBn BnO OBn O O O BnO BnO O C 13 H 27 OBz N 3 Ph O O OBn BnO OBn O HO OBn BnO BnO O C 13 H 27 OBz N 3 O O O NapO BnO Si SPh