Ingrid 't Hart

101 Chemoenzyma�c synthesis of heptose-ganglioside mimics 5 H-7a), 3.78 – 3.65 (3H, m, H-5; CH H , H-7b; H-2), 3.61 – 3.49 (1H, m, CH H , pentyl), 3.32 – 3.07 (3H, m, CH H + CH 2 , pentyl), 2.37 (2H, d, J = 9.8 Hz, O H ), 1.51 – 1.35 (4H, m, 2 x CH 2 , pentyl), 1.23 – 1.05 (2H, m, CH 2 , pentyl). 13 C NMR (151 MHz, CDCl 3 ) δ 138.7, 138.1, 137.9, 137.8, 136.2, 133.3, 132.9, 128.6, 128.4, 128.3, 128.1, 128.0, 127.9, 127.7, 127.7, 127.6, 127.6, 126.3, 125.9, 125.8, 96.6 (C-1), 78.5 (C-2), 76.3 (C-4), 75.1 (C-6), 74.5, 73.4, 72.8, 72.7, 72.3 (C-3), 70.6 (C-5), 70.3, 70.1, 67.3, 67.2, 50.5, 50.2, 47.1, 46.1, 29.2, 28.0, 27.6, 23.4. ESI HRMS ( m/z ): [M + NH 4 ] + calcd for C 59 H 63 NO 9 ; 947.4841 found 947.4884. N -(Benzyl)-benzyloxycarbonyl-5-aminopentyl 2,3,4,6-tetra- O -benzoyl-β-D- galactopyranosyl-(1 → 3)-2,6,7-tetra- O -benzyl-4- O -(2-naphthyl)methyl-L- glycero -α- D- manno heptopyranoside (7). A mixture of acceptor 6 (83 mg, 0.089 mmol), donor 5 (99 mg, 0.134 mmol) and 4 Å molecular sieves was s�rred in DCM (1.5 mL) for 1 h. The reac�on was cooled to -10 °C and TMSOTf (1.6 µL, 0.1 mmol in 100 µL DCM) was added. A�er 1 h the reac�on was quenched with Et 3 N (at 0 °C), filtered over Celite and concentrated in vacuo . The obtained residue was purified by silica column chromatography using Toluene:EtOAc as the eluent (1:0 to 10:1 v/v) and SX1 chromatography using Toluene:Acetone as the eluent (1:1 v/v) to afford compound 7 (85 mg, 66 %). 1 H NMR (600 MHz, CDCl 3 ) δ 8.00 – 7.10 (50H, m, H-Ar), 7.06 – 6.98 (2H, m, H-Ar), 5.94 (1H, s, H-4, Gal-II), 5.93 – 5.87 (1H, m, H-2, Gal-II), 5.60 (1H, dd, J = 10.3, 3.3 Hz, H-3, Gal-II), 5.33 (1H, d, J = 11.0 Hz, CH H ), 5.23 – 5.12 (2H, m, J = 23.4 Hz, CH 2 ), 5.08 (1H, s, H-1, Gal-II), 4.81 – 4.71 (2H, m, H-1, Hep-I; CH H ), 4.53 – 4.18 (13H, m, 4 x CH 2 ; H-6, Gal-II; H-3, Hep-I; H-4, Hep-I; H-5, Gal-II), 4.16 – 4.09 (1H, m, H-6, Hep-I), 3.81 – 3.73 (2H, m, H-5, Hep-I; H-7a, Hep-I), 3.71 (2H, s, H-2, Hep-I; H-7b, Hep-I), 3.49 (1H, s, CH H ), 3.16 (3H, d, J = 40.6 Hz, CH 2 , CH H , pentyl), 1.50 – 1.29 (4H, m, 2 x CH 2 , pentyl), 1.10 (2H, dd, J = 37.4, 8.1 Hz, CH 2 , pentyl). 13 C NMR (151 MHz, CDCl 3 ) δ 165.9 (C=O, Bz), 165.6 (C=O, Bz), 165.5 (C=O, Bz), 165.1 (C=O, Bz), 138.8, 138.2, 133.5, 133.3, 133.2, 132.8, 129.9, 129.8, 129.8, 129.7, 129.4, 129.2, 129.1, 129.0, 128.8, 128.6, 128.6, 128.4, 128.4, 128.3, 128.3, 128.3, 128.0, 128.0, 127.9, 127.7, 127.6, 127.5, 127.3, 127.2, 125.9, 125.6, 125.3, 99.9 (C-1, Gal-II), 97.6 (C-1, Hep-I), 80.1 (C-3, Hep-I), 76.0 (C-2, Hep-I), 75.0 (C-6, Hep-I), 74.4, 73.4 (C-4, Hep-I), 72.82, 72.72, 72.1 (C-3, Gal-II), 71.6 (C-5, Hep-I), 71.2 (C-5, Gal- II), 70.4 (C-2, Gal-II), 68.0 (C-4, Gal-II), 67.2, 67.2, 61.6, 50.5, 50.2, 47.1, 46.1, 29.0, 27.9, 27.6, 23.4, 23.3, 21.5. ESI HRMS ( m/z ): [M + NH 4 ] + calcd for C 93 H 89 NO 18 ; 1525.6418 found 1525.6489 5-Aminopentyl β-D-Galactopyranosyl-(1 → 3)-L- glycero -α-D- manno heptopyranoside (1). Freshly prepared NaOMe inMeOH (1 mL) was added to a solu�on of disaccharide 7 in DCM/MeOH (1 mL/2 mL). The mixture was s�rred overnight, neutralized with Amberlite H + resin, filtered and concentrated in vacuo . The obtained intermediate was dissolved in MeOH/ H 2 O/HOAc (2.5/0.5/0.5 mL), followed by addi�on of Pd(OH) 2 /C (60 mg) and the reac�on mixture was s�rred overnight under a hydrogen atmosphere. A�er that �me, it was filtered over Celite, concentrated in vacuo and the residue purified by BioGel P-2 column chromatography using BuOH:H 2 O (5:95 v/v) as the eluent to give the desired product 1 OBn O O BzO OBz BzO BzO BnO BnO NapO O O NBnCbz OH O O HO OH HO HO HO HO HO O O NH 2