Ingrid 't Hart

67 Synthesis of globo-series glycolipids 3 2,2,2-Trichloroace�midate 2,3,4,6-tetra- O -acetyl-β-D-galactopyranosyl-(1→3)-4,6- O - acetyl-2-[(2,2,2-trichloroethoxy)carbonylamino]-β-D-galactopyranosyl-(1→3)-2- O - benzyl-4,6- O- di- tert- butyl-silanediyl-α-D-galactopyranosyl-(1→4)-2,3,6-tri- O -benzyl- β-D-galactopyranosyl-(1→4)-2,3,6-tri- O -benzyl-β-D-glucopyranoside (11). Oven-dried ceric ammonium nitrate (63 mg, 0.122 mmol) was added to a s�rring solu�on of compound 10 in CH 3 CN (2.4 mL)/H 2 O (0.4 mL) at 0 °C. A�er 45 min the mixture was quenched by addi�on of sat. aq. NaHCO3 and diluted with DCM. The layers were separated and the organic layer was washed with sat. aq. NaHCO3 (2 x), H2O, dried (Na2SO4), 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 provide the product and star�ng material. The star�ng material was submi�ed again in the same manner as described before and this was repeated 3x. 2,2,2-Trichloroacetonitrile (34 µL, 0.343 mmol) and DBU (2 µL, 0.014 mmol) were added to the intermediate (139 mg, 0.069 mmol) in DCM (1.5 mL) with 4 Å molecular sieves at 0 °C. A�er 4.5 h the mixture was purified by silica column chromatography using Hexane:EtOAc (1:0 to 4:6 v/v) as the eluent to isolate compound 11 . Compound 11 was directly used in the next step. (2S,3R,4E)-2-azido-3-O-benzoyloxy-octadec-4-enyl 2,3,4,6-tetra- O -acetyl-β-D- galactopyranosyl-(1→3)-4,6- O -acetyl-2-[(2,2,2-trichloroethoxy)carbonylamino]- β-D-galactopyranosyl-(1→3)-2- O -benzyl-4,6- O- di- tert- butyl-silanediyl-α-D- galactopyranosyl-(1→4)-2,3,6-tri- O -benzyl-β-D-galactopyranosyl-(1→4)-2,3,6-tri- O - benzyl-β-D-glucopyranoside (12). A mixture of acceptor 5 (15 mg, 0.035 mmol) and donor 11 (100 mg, 0.046 mmol) was co-evaporated with toluene (3 x) and dried under high vacuum overnight. The dried compound mixture was s�rred with 4 Å molecular sieves in DCM for 1.5 h. The mixture was cooled to -50 °C and BF 3 OEt 2 (0.4 µL in 100µL DCM, 0.0035 mmol) was added. A�er 3 h the reac�on was quenched by addi�on of Et 3 N. The mixture was filtered over Celite and concentrated in vacuo . The obtained residue was purified by silica gel chromatography using Toluene:EtOAc (1:0 to 8:2 v/v) as the eluent. Subsequent purifica�on by Biogel SX-1 using Toluene:Acetone (1:1 v/v) as the eluent provided the β-anomer of the �tle compound. 1 H NMR (600 MHz, CDCl 3 ) δ 8.05 (2H, d, J = 7.6 Hz, H-Ar), 7.58 – 7.11 (38H, m, H-Ar), 5.89 – 5.81 (1H, m, CH=C H -CH 2 ), 5.62 (1H, dd, J = 7.8, 4.1 Hz, C H OBz), 5.53 (1H, dd, J = 15.3, 7.9 Hz, CHOBz-C H =CH), 5.36 (1H, d, J = 3.1 Hz, H-4, Gal-V), 5.21 (1H, d, J = 3.0 Hz, H-4, Gal-IV), 5.07 – 4.98 (2H, m, H-2, Gal-V), 4.94 (1H, d, J = 11.7 Hz, CH H ), 4.89 – 4.77 (4H, m, H-3, Gal-V; H-1, Gal-III), 4.75 – 4.64 (4H, m), 4.59 (1H, s, H-4, Gal-III), 4.56 – 4.42 (5H, m, H-1, Gal-II; H-1, Gal-V), 4.41 – 4.11 (9H, m, H-1, Glc-I, H-1, GalNAc-IV), 4.10 – 3.71 (15H, m, H-4, Glc-I; C H N 3 ; H-4, Gal-II; H-2, Gal- III; H-5, Gal-V; H-3, Gal-III), 3.68 – 3.46 (7H, m, H-2, Gal-II; H-3, GalNac-IV; H-3, Glc-I), 3.41 (1H, t, J = 8.4 Hz, H-2, Glc-I), 3.33 – 3.26 (3H, m, H-3, Gal-II), 2.16 (3H, s, CH 3 , OAc), 2.10 O AcO OAc O TrocHN O AcO OAc AcO AcO O O O O BnO O O OBn BnO OBn O O OBn BnO BnO Si O CCl 3 NH O AcO OAc O TrocHN O AcO OAc AcO AcO O O O O BnO O O OBn BnO OBn O O OBn BnO BnO Si O C 13 H 27 OBz N 3