HETEROCYCLES

Note | Regular issue | Vol. 81, No. 7, 2010, pp. 1711-1720
Received, 15th May, 2010, Accepted, 1st June, 2010, Published online, 1st June, 2010.
DOI: 10.3987/COM-10-11974

■ Synthesis of Galacto- and Mannosucroses

Atsushi Ueda, Takanori Yamashita, and Jun'ichi Uenishi*

Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan

Abstract

A concise synthesis of β-D-fructofuranosyl α-D-galactopyranoside (2), and β-D-fructofuranosyl α-D-mannopyranoside (3) is described. Inversion of the C-3 α-hydroxy group of α-D-galactopyranosyl and α-D-mannopyranosyl β-D-psicofuranosides 10 and 11 via oxidation and stereoselective reduction furnished the corresponding β-D-fructofuranosides in excellent yields.

(+)-Sucrose (1) is the most popular disaccharide and an important nutriment for human life. Its structure is categorized as a non-reducing disaccharide, of which β-D-fructofuranosyl bond is connected with α-D-glucose at each anomeric position. β-D-Fructofuranosyl disaccharides1 containing D-galactose and D-mannose instead of D-glucose are called galactosucrose (2)2,3 and mannosucorse (3).3a,3b,4 However, they have received less attention. Since we have found an excellent β-D-psicofuranosyl donor for the glycosylation reaction with D-glucose accepter, the stereoselective synthesis of 1 was performed by the stereo-inversion of α-D-glucopyranosyl β-D-psicofuranoside to β-D-fructofuranosyl α-D-glucopyrano- side.5 More recently, we have reported the synthesis of α-D-glucopyranosyl β-D-psicofuranoside (4), α-D-galactopyranosyl β-D-psicofuranoside (5), and α-D-mannopyranosyl β-D-psicofuranoside (6).6

Because α-D-galactopyranosyl β-D-psicofuranoside and α-D-mannopyranosyl β-D-psicofuranoside are in hand, the same stereo-inversion as reported for the synthesis of 1 would provide the corresponding galacto- and mannosucorose (2) and (3). In this note, we describe the synthesis of 2 and 3 via stereoselective β-D-psicosylation and stereo-conversion of the C-3 α-hydroxy group to β-hydroxy group on the furanose ring.

In our recent report for the synthesis of α-D-hexopyranosyl β-D-psicofuranosides 4–6,6 glycosylation of D-hexopyranose with psicofuranosyl donor 9 gave the corresponding disaccharides. Galactopyranosyl psicosides 10 and 10’ and mannopyranosyl psicosides 11 and 11’ were prepared respectively, as shown in Scheme 1.

In order to synthesize 2 and 3, the C-3 α-hydroxy group on the β-D-psicofuranosyl ring in 10 and 11, must be inverted to β-orientation (Scheme 2). For this purpose, differentiation of the C-3 or C-4 α-hydroxy group was necessary. Treatment of the vicinal 3,4-diol of 10 with dibutyltin oxide gave a stannylene intermediate, which underwent monobenzoylation with benzoyl chloride in the presence of Et3N to give 12 in 74% yield.7 Similarly, compound 11 was converted to 13 in 75% yield. Swern oxidation of the C-3 hydroxy group for 12 and 13 afforded carbonyl compounds 14 and 15 in 93 and 96% yields, respectively. Reduction of the carbonyl group by NaBH4 was carried out in a 1:1 mixture of CH2Cl2 and MeOH at 0 ºC. Because of presence of the axial β-glycosyl bond, a hydride attacks to carbonyl face from the bottom side of the ring selectively to give C-3 β-hydroxy group (Scheme 3).8 In fact, compounds 16 and 17 were obtained from 14 and 15 in 96 and 86% yields, respectively.

These oxidation and reduction steps furnished the conversion of β-D-psicofuranose ring to β-D-fructofuranose ring in excellent yields. Steps remaining to 2 or 3 require deprotections of three O-benzoyl and four O-benzyl groups. First, we examined deprotection of all the protecting groups at once. Compound 16 was subjected to Birch reduction conditions in liq. ammonia and resulted crude product was acetylated with acetic anhydride in pyridine to give octaacetate 18 in 97% yield. Removal of all acetyl groups of 18 under Zempén’s condition gave galactosucrose (2) in 96% yield. Physical and spectroscopic data of both 18 and 2 were accorded with those reported in literature.2a By the same two steps, compound 17 afforded mannosucrose (3) via octaacetate 19 in quantitaive yield. Alternatively, stepwise deprotections of compound 17 also gave 3 in excellent yield. Methanolysis of three benzoates of 17 gave tetraol 20 in 88% yield. Hydrogenolysis of the remaining O-benzyl groups afforded the desired compound 3 in 90% yield. These spectroscopic and physical data of 3 are in accordance of those reported previously.4

In conclusion, conversion of α-D-hexopyranosyl β-D-psicofuranoside to α-D-hexopyranosyl β-D-fructofuranoside has been performed and chemically pure galacto- and mannosucroses were obtained in high yields. Although the chemical conversion to these two disacharides from (+)-sucrose were reported, they have been synthesized for the first time via glycosidation pathway. This synthetic route will be useful for a general synthesis of α-D-hexopyranosyl β-D-fructofuranoside.

EXPERIMENTAL
General. Specific rotations were measured on a JASCO P-2200 polarimeter using CHCl3, MeOH, or H2O as a solvent. 1H NMR and 13C NMR spectra were measured on JEOL JNM-AL-300 (300 MHz and 75 MHz), JEOL JNM-ECA 600 (600 MHz and 150 MHz), or Varian UNITY INOVA 400 NB (400 MHz and 100 MHz) spectrometer. Chemical shifts (δ) are reported in parts per million (ppm) relative to the resonance of the solvent or to tetramethylsilane (0.00 ppm) for 1H NMR spectra and ppm relative to the resonance of the solvent or to MeCN (1.47 ppm) when D2O was used, for 13C NMR spectra. IR spectra were recorded on a JASCO FT/IR-410 spectrophotometer. Low and high-resolution mass spectra (LRMS and HRMS) were obtained on a JEOL JMS 303HF spectrometer using fast atom bombardment (FAB) ionization. Silica gel (230–400 mesh) was used for flash chromatography. Analytical thin-layer chromatography (TLC) was performed on glass pre-coated with silica gel (0.25 mm thickness). All moisture sensitive reactions were carried out under an argon atmosphere. THF was dried over sodium/benzophenone ketyl, and CH2Cl2 was dried over P2O5, and they were distilled prior to use.

2,3,4,6-Tetra-O-benzyl-α-D-galactopyranosyl 1,4,6-tri-O-benzoyl-β-D-psicofuranoside (12): A mixture of diol 10 (53.6 mg, 58.8 µmol) and Bu2SnO (14.6 mg, 58.8 µmol) in MeOH (3.9 mL) was heated at reflux for 45 min. To the reaction mixture were added Et3N (82 µL, 588 µmol) and benzoyl chloride (68 µL, 588 µmol) 0 °C and then the mixture was stirred for 10 min at the same temperature. After evaporation of solvent, the crude product was purified by silica gel flash chromatography eluted with 15% EtOAc in hexane to give 12 (44.3 mg, 74%) as a colorless syrup. Rf = 0.43 (30% EtOAc in hexane). [α]22D +41.3 (c 0.90, CHCl3). 1H NMR (300 MHz, CDCl3) δ: 8.08–8.00 (6H, m), 7.60–7.15 (29H, m), 5.64 (1H, d, J1’,2’ = 3.7 Hz, H-1’), 5.48 (1H, t, J3,4 = J4,5 = 4.9 Hz, H-4), 4.94–4.88 (3H, m), 4.73–4.62 (5H, m), 4.57–4.46 (5H, m), 4.38 (1H, d, J = 11.9 Hz), 4.21 (1H, ddd, J5’,6’a = 8.5, J5’,6’b = 3.0, J4’,5’ = 0.7 Hz, H-5’), 4.05 (1H, d, J = 5.1 Hz, OH), 4.00 (1H, dd, J2’,3’ = 10.1, J1’,2’ = 3.7 Hz, H-2’), 3.86 (1H, dd, J2’,3’ = 10.1, J3’,4’ = 2.6 Hz, H-3’), 3.78 (1H, dd, J3’,4’ = 2.6, J4’,5’ = 0.7 Hz, H-4’), 3.59 (1H, dd, J6’a,6’b = 9.6, J5’,6’a = 8.5 Hz, H-6’a), 3.26 (1H, dd, J6’a,6’b = 9.6, J5’,6’b = 3.0 Hz, H-6’b). 13C NMR (75 MHz, CDCl3) δ: 167.0, 166.1, 165.7, 138.8, 138.4, 138.2, 137.1, 133.3, 133.0, 132.8, 130.0, 129.9, 129.8, 129.7, 129.5, 129.3, 128.4, 128.3, 128.3, 128.3, 128.1, 128.1, 128.0, 128.0, 127.9, 127.7, 127.6, 127.3, 127.3, 107.5, 90.3, 79.1, 78.8, 75.6, 75.4, 74.3, 73.6, 73.5, 73.3, 72.3, 72.2, 70.5, 70.3, 65.2, 63.4. IR (film): 3424, 3019, 1721, 1453, 1272, 1095, 1026, 712 cm−1. MS (FAB) m/z: 1037 [M+Na]+. HRMS (FAB) m/z: Calcd for C61H58O14Na, 1037.3724; found, 1037.3716.

2,3,4,6-Tetra-O-benzyl-α-D-mannopyranosyl 1,4,6-tri-O-benzoyl-β-D-psicofuranoside (13): Com- pound 13 was obtained from 11 by the same manner described for the synthesis of 12 in 75% yield as a colorless syrup. Rf = 0.70 (40% EtOAc in hexane). [α]20D +4.8 (c 1.00, CHCl3). 1H NMR (400 MHz, CDCl3) δ: 8.07–8.03 (4H, m), 7.94–7.91 (2H, m), 7.59–7.13 (29H, m), 5.53 (1H, d, J1’,2’ = 1.6 Hz, H-1’), 5.43 (1H, dd, J4,5 = 5.5, J3,4 = 5.4 Hz, H-4), 4.85 (1H, d, J = 10.8 Hz), 4.82 (1H, dd, J3,4 = 5.4, J3,OH = 5.2 Hz, H-3), 4.75 (1H, d, J = 12.5 Hz), 4.73 (1H, dd, J6a,6b = 11.5, J5,6a = 5.7 Hz, H-6a), 4.66 (1H, ddd, J5,6a = 5.7, J4,5 = 5.5, J5,6b = 3.8 Hz H-5), 4.64 (1H, d, J = 12.4 Hz), 4.59 (1H, d, J = 12.3 Hz), 4.58 (1H, d, J = 12.4 Hz), 4.55 (1H, dd, J6a,6b = 11.5, J5,6b = 3.8 Hz, H-6b), 4.51 (1H, d, J = 12.3 Hz), 4.47 (1H, d, J = 10.8 Hz), 4.45 (1H, d, J = 12.5 Hz), 4.34 (2H, s), 4.13–4.08 (1H, m, H-5’), 3.97 (1H, d, J3,OH = 5.2 Hz, OH), 3.87–3.77 (4H, m, H-2’, 3’, 4’, 6’a), 3.63 (1H, dd, J = 9.9, 7.0 Hz, H-6’b). 13C NMR (75 MHz, CDCl3) δ: 166.6, 166.2, 165.7, 138.2, 138.1, 138.0, 137.6, 133.4, 133.3, 133.1, 129.9, 129.7, 129.6, 129.5, 129.2, 128.5, 128.4, 128.3, 128.2, 128.0, 127.9, 127.8, 127.7, 127.62, 127.57, 127.5, 127.4, 107.6, 91.1, 80.1, 79.0, 75.0, 74.8, 74.3, 74.0, 73.4, 72.4, 72.3 (2C), 71.8, 69.4, 65.5, 62.6. IR (film): 3456, 3031, 2918, 1724, 1601, 1496, 1453, 1273, 1110, 741, 711 cm−1. MS (FAB) m/z: 1037 [M+Na]+. HRMS (FAB) m/z: Calcd for C61H58O14Na, 1037.3724; found, 1037.3717.

1,4,6-Tri-O-benzoyl-β-D-erythro-2,3-hexodiulofuranosyl 2,3,4,6-tetra-O-benzyl-α-D-galactopyranoside (14): A solution of DMSO (16.0 µL, 226 µmol) in CH2Cl2 (0.2 mL) was added to a solution of oxalyl chloride (9.9 µL, 113 µmol) in CH2Cl2 (1.5 mL) at −78 °C and the reaction was stirred for 15 min at the same temperature. To this mixture was added disaccharide 12 (38.3 mg, 37.7 µmol) in CH2Cl2 (1.2 mL) at −78 °C and the whole was stirred for 1 h at same temperature prior to the addition of Et3N (63 µL, 0.45 mmol). The reaction was allowed to warm up to rt and sat. aqueous NH4Cl solution was added to the mixture. The aqueous layer was extracted with EtOAc and combined organic layer was washed with water and brine, dried over MgSO4, and evaporated under vacuum. The residue was purified by flash chromatography on silica gel eluted with 20% EtOAc in hexane to give 14 (35.5 mg, 93%) as a colorless syrup. Rf = 0.50 (30% EtOAc in hexane). [α]22D +52.1 (c 1.04, CHCl3). 1H NMR (300 MHz, CDCl3) δ: 8.07–7.94 (6H, m), 7.65–7.56 (2H, m), 7.45–7.03 (27H, m), 6.27 (1H, d, J4’,5’ = 8.3 Hz, H-4’), 5.77 (1H, d, J1,2 = 3.7 Hz, H-1), 4.97 (1H, d, J = 10.5 Hz), 4.86 (1H, d, J = 11.7 Hz), 4.78–4.72 (4H, m), 4.67–4.44 (5H, m), 4.65 (1H, ddd, J4’,5’ = 8.3, J5’,6’b = 2.8, J5’,6’a = 2.6 Hz, H-5’), 4.58 (1H, dd, J6’a,6’b = 11.9, J5’,6’a = 2.6 Hz, H-6’a), 4.12 (1H, dd, J3,4 = 2.1, J4,5 = 0.7 Hz, H-4), 3.97 (1H, dd, J2,3 = 10.3, J1,2 = 3.7 Hz, H-2), 3.90 (1H, dd, J2,3 = 10.3, J3,4 = 2.1 Hz, H-3), 3.82 (1H, ddd, J5,6a = 8.9, J5,6b = 4.8, J4,5 = 0.7 Hz, H-5), 3.70 (1H, dd, J5,6a = 8.9, J6a,6b = 8.8 Hz, H-6a), 3.41 (1H, dd, J6a,6b = 8.8, J5,6b = 4.8 Hz, H-6b). 13C NMR (75 MHz, CDCl3) δ: 205.7, 166.1, 165.0, 164.8, 138.7 (2C), 138.1, 137.9, 133.8, 133.3, 133.2, 129.9, 129.7, 129.6, 129.3, 128.9, 128.5, 128.4, 128.3, 128.2, 128.2, 128.1, 127.8, 127.7, 127.5, 127.5, 127.4, 127.4, 127.3, 97.7, 90.7, 78.1, 75.8, 75.2, 74.7, 74.7, 73.3, 73.0, 72.9, 69.8, 68.9, 66.9, 66.9, 63.1. IR (film): 2923, 1783, 1729, 1601, 1452, 1268, 1094, 752, 709 cm−1. MS (FAB) m/z: 1035 [M+Na]+. HRMS (FAB) m/z: Calcd for C61H56O14Na, 1035.3568; found 1035.3575.

1,4,6-Tri-O-benzoyl-β-D-erythro-2,3-hexodiulofuranosyl 2,3,4,6-tetra-O-benzyl-α-D-mannopyranoside (15): Compound 15 was obtained from 13 by the same manner described for the synthesis of 14 in 96% yield as a colorless syrup. Rf = 0.60 (30% EtOAc in hexane). [α]20D +67.0 (c 1.00, CHCl3). 1H NMR (400 MHz, CDCl3) δ: 8.19–8.17 (2H, m), 8.04–7.98 (4H, m), 7.63–7.55 (2H, m), 7.46–7.11 (27H, m), 6.41 (1H, d, J4’,5’ = 8.4 Hz, H-4’), 5.78 (1H, d, J1,2 = 1.6 Hz, H-1), 4.91 (1H, d, J = 10.8 Hz), 4.79 (1H, dd, J = 12.4, 2.4 Hz), 4.70–4.52 (8H, m), 4.46 (1H, d, J = 11.6 Hz), 4.44 (1H, d, J = 12.4 Hz), 4.38 (1H, d, J = 12.4 Hz), 4.26 (1H, t, J3,4 = J4,5 = 9.6 Hz, H-4), 3.84 (1H, dd, J3,4 = 9.6, J2,3 = 3.1 Hz, H-3), 3.82–3.77 (1H, m, H-5), 3.75 (1H, dd, J2,3 = 3.1, J1,2 = 1.6 Hz), 3.57 (2H, d, J5,6 = 10.8 Hz, H-6). 13C NMR (100 MHz, CDCl3) δ: 205.0, 166.4, 165.1, 164.8, 138.6, 138.5, 138.4, 137.7, 133.8, 133.4, 133.2, 130.0, 129.7, 129.2, 129.0, 128.6, 128.5, 128.3, 128.2, 127.9, 127.6, 127.5, 127.3, 97.4, 91.7, 79.4, 76.0, 75.1, 74.2, 74.1, 73.5, 73.1, 72.6, 72.4, 69.3, 68.3, 66.7, 63.2. IR (film): 3065, 3031, 2916, 2865, 1785, 1731, 1602, 1496, 1452, 1365, 1268, 1110, 739, 709 cm−1. MS (FAB) m/z: 1035 [M+Na]+. HRMS (FAB) m/z: Calcd for C61H56O14Na, 1035.3568; found, 1035.3573.

1,4,6-Tri-O-benzoyl-β-D-fructofuranosyl 2,3,4,6-tetra-O-benzyl-α-D-galactopyranoside (16): To a solution of 14 (32.0 mg, 31.5 µmol) in MeOH–CH2Cl2 (1:1, 2.0 mL), was added sodium borohydride (2.4 mg, 63 µmol) at 0 °C, and the reaction mixture was stirred for 30 min at the same temperature. The reaction was quenched with sat. aqueous NH4Cl solution and extracted with EtOAc. The organic layer was washed with water and brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel eluted with 20% EtOAc in hexane to give disaccharide 16 (30.6 mg, 96%) as a colorless syrup. Rf = 0.43 (30% EtOAc in hexane). [α]23D +29.0 (c 1.06, CHCl3). 1H NMR (300 MHz, CDCl3) δ: 8.06–8.02 (6H, m), 7.61–7.17 (29H, m), 5.80 (1H, d, J1,2 = 3.7 Hz, H-1), 5.70 (1H, t, J3’,4’ = J4’,5’ = 7.4 Hz, H-4’), 4.94 (1H, d, J = 11.4 Hz), 4.79 (1H, d, J = 11.9 Hz), 4.73–4.29 (13H, m), 4.12 (1H, ddd, J5,6a = 7.2, J5,6b = 5.5, J4,5 = 0.9 Hz, H-5’), 4.07 (1H, dd, J2,3 = 10.1, J1,2 = 3.7 Hz, H-2), 3.98 (1H, dd, J2,3 = 10.1, J3,4 = 2.4 Hz, H-3), 3.93 (1H, dd, J3,4 = 2.4, J4,5 = 0.9 Hz, H-4), 3.59 (1H, dd, J6a,6b = 9.2, J5,6a = 7.2 Hz, H-6a), 3.45 (1H, dd, J6a,6b = 9.2, J5,6b = 5.5 Hz, H-6b). 13C NMR (75 MHz, CDCl3) δ: 166.1, 165.8, 165.7, 138.4 (2C), 137.7, 137.6, 133.4, 133.1, 132.9, 129.8, 129.7, 129.7, 129.6, 129.1, 128.3, 128.3, 128.3, 128.3, 128.2, 128.2, 128.0, 127.8, 127.6, 127.5, 127.5, 127.5, 104.2, 91.5, 78.7, 77.7, 77.5, 77.2, 75.1, 74.9, 74.7, 73.4, 73.2, 72.8, 70.6, 69.2, 64.5, 64.3. IR (film): 3449, 3018, 1724, 1453, 1269, 1096, 711 cm−1. MS (FAB) m/z: 1037 [M+Na]+. HRMS (FAB) m/z: Calcd for C61H58O14Na, 1037.3724; found 1037.3717.

1,4,6-Tri-O-benzoyl-β-D-fructofuranosyl 2,3,4,6-tetra-O-benzyl-α-D-mannopyranoside (17): Com- pound 17 was obtained from 15 by the same reaction manner described for the synthesis of 16 in 86% yield as a colorless syrup. Rf = 0.52 (30% EtOAc in hexane). [α]20D +23.3 (c 1.00, CHCl3). 1H NMR (400 MHz, CDCl3) δ: 8.05–7.97 (6H, m), 7.58–7.55 (2H, m), 7.46–7.41 (5H, m), 7.32–7.22 (17H, m), 7.21–7.11 (5H, m), 5.70 (1H, d, J = 2.2 Hz, H-1), 5.65 (1H, dd, J3’,4’ = 7.7, J4’,5’ = 7.5 Hz, H-4’), 4.85 (1H, d, J = 11.0 Hz), 4.68–4.47 (7H, m), 4.65 (1H, dd, J6’a,6’b = 12.1, J5’,6’a = 6.2 Hz, H-6’a), 4.54 (1H, dd, J6’a,6’b = 12.1, J5’,6’b = 4.4 Hz, H-6’b), 4.53 (1H, dd, J3’,OH = 8.8, J3’,4’ = 7.7 Hz, H-3’), 4.39 (1H, d, J = 11.7 Hz), 4.38 (1H, ddd, J4’,5’ = 7.5, J5’,6’a = 6.2, J5’,6’b = 4.4 Hz, H-5’), 4.34 (1H, d, J = 11.7 Hz), 4.15 (1H, ddd, J4,5 = 9.2, J5,6b = 6.4, J5,6a = 1.8 Hz, H-5), 3.92 (1H, dd, J4,5 = 9.2, J3,4 = 8.8 Hz, H-4), 3.89 (1H, dd, J3,4 = 8.8, J2,3 = 2.7 Hz, H-3), 3.77 (1H, dd, J6a,6b = 10.3, J5,6a = 1.8 Hz, H-6a), 3.72 (1H, dd, J2,3 = 2.7, J1,2 = 2.2 Hz, H-2), 3.67 (1H, dd, J6a,6b = 10.3, J5,6b = 6.4 Hz, H-6b), 3.63 (1H, d, J3,OH = 8.8 Hz, OH). 13C NMR (75 MHz, CDCl3) δ: 166.1, 165.9, 165.7, 138.2, 138.1, 137.9, 137.8, 133.5, 133.3, 133.0, 129.9, 129.8, 129.7, 129.5, 129.4, 128.9, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6,127.5, 127.4, 127.3, 127.2, 103.9, 91.3, 79.2, 77.6, 77.5, 77.0, 75.0, 74.8, 74.7, 73.3, 72.9, 72.5, 72.1, 69.2, 64.6 (2C). IR (film): 3479, 3032, 2916, 1729, 1602, 1496, 1453, 1268, 1096, 709 cm−1. MS (FAB) m/z: 1037 [M+Na]+. HRMS (FAB) m/z: Calcd for C61H58O14Na, 1037.3724; found, 1037.3721.

1,3,4,6-Tetra-O-acetyl-β-D-fructofuranosyl 2,3,4,6-tetra-O-acetyl-α-D-galactopyranoside (18): Liq. NH3 (4 mL) was condensed into a 2-necked flask at −78 °C and to which was added ca. 30 mg of sodium metal. To the resultant dark blue solution was added a solution of 16 (28.9 mg, 28.4 µmol) in THF (2 mL) and the mixture was vigorously stirred for 30 min at the same temperature. The reaction was quenched with acetic acid (0.1 mL) and MeOH (3 mL). Solvent was removed and the residue was acetylated in pyridine (5 mL) with acetic anhydride (1 mL) in presence of 4-(dimethylamino)pyridine (10 mg) overnight at rt. The reaction mixture was condensed and the residue was purified by flash chromatography on silica gel eluted with 50% EtOAc in hexane to give 18 (18.9 mg, 97%) as a colorless syrup. Rf = 0.45 (60% EtOAc in hexane). [α]23D +56.1 (c 0.83, CHCl3). 1H NMR (300 MHz, CDCl3) δ: 5.72 (1H, d, J1,2 = 3.7 Hz, H-1), 5.49 (1H, d, J4’,5’ = 6.6 Hz, H-4’), 5.49–5.45 (1H, m), 5.38 (1H, dd, J = 6.6, 6.4 Hz), 5.34 (1H, dd, J2,3 = 11.0, J3,4 = 3.3 Hz, H-3), 5.15 (1H, dd, J2,3 = 11.0, J1,2 = 3.7 Hz, H-2), 4.49 (1H, t, J = 6.1 Hz), 4.34–4.31 (2H, m), 4.23–4.04 (5H, m), 2.14 (3H, s), 2.13 (3H, s), 2.11 (3H, s), 2.11 (3H, s), 2.10 (3H, s), 2.09 (3H, s), 2.06 (3H, s), 1.99 (3H, s). 13C NMR (75 MHz, CDCl3) δ: 170.4 (2C), 170.3, 170.1, 170.0, 169.9, 169.9, 169.7, 103.5, 90.3, 78.6, 75.3, 74.5, 67.9, 67.4, 67.3, 67.0, 63.9, 63.0, 61.6, 20.7 (2C), 20.6 (2C), 20.59 (2C), 20.56, 20.53. IR (film): 2965, 1748, 1372, 1228, 1053, 756 cm−1. MS (FAB) m/z: 701 [M+Na]+. HRMS (FAB) m/z: Calcd for C28H38O19Na, 701.1905; found, 701.1911.

1,3,4,6-Tetra-O-acetyl-β-D-fructofuranosyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside (19): Compound 19 was obtained from 17 by the same reaction manner described for the synthesis of 18 in quantitative yield as a colorless syrup. Rf = 0.19 (50% EtOAc in hexane). [α]20D –8.4 (c 0.30, CHCl3). 1H NMR (400 MHz, CDCl3) δ: 5.44 (1H, d, J3’,4’ = 6.6 Hz, H-3’), 5.43 (1H, d, J1,2 = 2.1 Hz, H-1), 5.40 (1H, dd, J3’,4’ = 6.6, J4’,5’ = 6.4 Hz, H-4’), 5.34 (1H, dd, J3,4 = 10.1, J2,3 = 2.9 Hz, H-3), 5.31 (1H, dd, J3,4 = 10.1, J4,5 = 9.9 Hz, H-4), 5.12 (1H, dd, J2,3 = 2.9, J1,2 = 2.1 Hz, H-2), 4.36 (1H, dd, J = 11.9, 4.6 Hz), 4.32–4.23 (3H, m), 4.27 (1H, d, J1’a,1’b = 12.3 Hz, H-1’a), 4.22–4.17 (2H, m), 4.18 (1H, d, J1’a,1’b = 12.3 Hz, H-1’b), 2.17 (3H, s), 2.16 (3H, s), 2.11 (3H, s), 2.10 (3H, s), 2.10 (3H, s), 2.09 (3H, s), 2.06 (3H, s), 1.99 (3H, s). 13C NMR (75 MHz, CDCl3) δ: 170.7, 170.5, 170.0, 170.0, 169.9, 169.8, 169.7, 169.6, 103.5, 91.3, 78.7, 76.0, 74.8, 70.1, 69.9, 68.7, 65.6, 63.7, 63.5, 62.3, 20.9, 20.8 (2C), 20.7 (3C), 20.6, 20.5. IR (film): 2960, 1747, 1437, 1371, 1223 cm−1. MS (FAB) m/z: 701 [M+Na]+. HRMS (FAB) m/z: Calcd for C28H38O19Na, 701.1905; found, 701.1911.

β-D-Fructofuranosyl α-D-galactopyranoside (2): A 5 µL of 1 M NaOMe in MeOH solution was added to 18 (17.4 mg, 25.6 µmol) in MeOH (0.5 mL), and the reaction was stirred for 3 h at rt. The reaction mixture was neutralized with Dowex 50W × 2. After filtration through a pad of Celite, the filtrate was concentrated under vacuum, dissolved in water, and lyophilized to afford galactosucrose (2, 8.5 mg, 96%) as a white solid. Rf = 0.32 (25% H2O in MeCN). [α]22D +72.4 (c 1.00, H2O). 1H NMR (400 MHz, D2O) δ: 5.43 (1H, d, J1,2 = 3.8 Hz, H-1), 4.20 (1H, d, J3’,4’ = 8.8 Hz, H-3’), 4.13 (1H, dd, J5,6b = 7.3, J5,6a = 5.6 Hz, H-5), 4.05 (1H, dd, J3’,4’ = 8.8, J4’,5’ = 7.9 Hz, H-4’), 4.01 (1H, d, J3,4 = 3.1 Hz, H-4), 3.91 (1H, dd, J2,3 = 10.3, J3,4 = 3.1 Hz, H-3), 3.88–3.79 (4H, m, H-5’, 6’a, 6’b, 2), 3.75 (1H, dd, J6a,6b = 11.8, J5,6a = 5.6 Hz, H-6a), 3.70 (1H, dd, J6a,6b = 11.8, J5,6b = 7.3 Hz, H-6b), 3.67 (2H, s, H-1’). 13C NMR (100 MHz, D2O) δ: 103.7, 92.4, 81.4, 76.6, 74.1, 71.5, 69.2, 69.2, 68.0, 62.4, 61.5, 60.9. IR (KBr): 3386, 1654, 1421, 1073 cm−1. MS (FAB) m/z: 365 [M+Na]+. HRMS (FAB) m/z: Calcd for C12H22O11Na, 365.1060; found, 365.1053.

β-D-Fructofuranosyl 2,3,4,6-tetra-O-benzyl-α-D-mannopyranoside (20): A mixed suspension of 17 (16.6 mg, 16.4 µmol) and K2CO3 (22.9 mg, 166 µmol) in MeOH (2.2 mL) was stirred for 1 h at rt. After filtration of the reaction mixture through a Celite pad, the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography eluted with EtOAc to give tetraol 20 (10.1 mg, 88%) as a white semisolid. Rf = 0.20 (EtOAc). [α]20D +8.6 (c 0.81, MeOH). 1H NMR (400 MHz, CD3OD) δ: 7.36–7.25 (18H, m), 7.24–7.13 (2H, m), 5.52 (1H, J1,2 = 2.2 Hz, H-1), 4.80 (1H, d, J = 11.0 Hz, CHHPh), 4.68 (2H, s, CH2Ph), 4.61 (1H, d, J = 12.1 Hz, CHHPh), 4.60–4.56 (2H, m, CH2Ph), 4.50 (1H, d, J = 11.0 Hz, CHHPh), 4.48 (1H, d, J = 12.1 Hz, CHHPh), 4.07 (1H, d, J3’,4’ = 8.8 Hz, H-3’), 4.01–3.86 (4H, m, H-4’, 5’, 6’a, 6’b), 3.78 (1H, dd, J6a,6b = 10.6, J5,6a = 5.5 Hz, H-6a), 3.78–3.63 (4H, m, 3, 4, 5, 6b), 3.72 (1H, dd, J2,3 = 2.6, J1,2 = 2.2 Hz, H-2), 3.42 (1H, d, J1’a,1’b = 11.9 Hz, H-1’a), 3.32 (1H, d, J1’a,1’b = 11.9 Hz, H-1’b). 13C NMR (150 MHz, CD3OD) δ: 139.8 (2C), 139.7, 139.6, 129.4, 129.3, 129.2, 129.1, 129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 105.7, 92.5, 83.8, 80.4, 77.9, 77.0, 75.9, 75.8, 75.3, 74.4, 73.6, 73.4, 73.1, 70.1, 63.6, 63.3. IR (film): 3417, 2922, 1454, 1071 cm−1. MS (FAB) m/z: 725 [M+Na]+. HRMS (FAB) m/z: Calcd for C40H46O11Na, 725.2938; found, 725.2934.

β-D-Fructofuranosyl α-D-mannopyranoside (3): Synthesis from 19. Compound 3 was obtained from 19 by the same reaction manner described for the synthesis of 2 in a quantitative yield as a white solid. Rf = 0.61 (25% H2O in MeCN). [α]20D +11.8 (c 0.44, H2O). 1H NMR (400 MHz, D2O) δ: 5.35 (1H, d, J1,2 = 2.0 Hz, H-1), 4.18 (1H, d, J3’,4’ = 8.8 Hz, H-3’), 4.06 (1H, dd, J3’,4’ = 8.8, J4’,5’ = 8.1 Hz, H-5’), 3.90 (1H, dd, J3,4 = 9.5, J2,3 = 3.3 Hz, H-3), 3.90–3.75 (6H, m, H-5, 6, 5’, 6’), 3.86 (1H, dd, J2,3 = 3.3, J1,2 = 2.0 Hz, H-2), 3.70 (1H, dd, J4,5 = 9.7, J3,4 = 9.5 Hz, H-4), 3.66 (2H, s, H-1’). 13C NMR (75 MHz, D2O) δ: 104.6, 94.3, 82.0, 76.6, 74.5, 74.0, 71.8, 70.8, 67.1, 63.0, 61.6, 61.3. IR (KBr): 3376, 2927, 1272, 1069 cm−1. Synthesis from 20. A suspension of 20 (10.1 mg, 14.4 µmol) and 20% Pd(OH)2 on carbon (10 mg) in MeOH (1 mL) was stirred overnight under H2 atmosphere. The reaction was filtered through a Celite pad and concentrated under vacuum to give (3, 4.4 mg, 90%) as a white solid.

References

1. Other natural saccharides containing a β-D-fructofuranosyl unit; for example (a) B. Lindberg, Adv. Carbohydr. Chem. Biochem., 1990, 48, 279; CrossRef (b) S. Kobayashi, T. Miyase, and H. Noguchi, J. Nat. Prod., 2002, 65, 319; CrossRef (c) A. Kato, N. Kato, S. Miyauchi, Y. Minoshima, I. Adachi, K. Ikeda, N. Asano, A. A. Watson, and R. J. Nash, Phytochemistry, 2008, 69, 1261. CrossRef
2. Chemical conversion from (+)-sucrose; (a) J. Seibel, R. Moraru, and S. Götze, Tetrahedron, 2005, 61, 7081; CrossRef (b) L. Hough and K. S. Mufti, Carbohydr. Res., 1973, 29, 291. CrossRef
3. Enzymatic transformation; (a) J. Seibel, R. Moraru, S. Götze, K. Buchholz, S. Na’amnieh, A. Pawlowski, and H.-J. Hecht, Carbohydr. Res., 2006, 341, 2335; CrossRef (b) S.-W. Nam, H.-J. Yun, J.-H. Ahn, K.-H. Kim, and B.-W. Kim, Biotechnol. Lett., 2000, 22, 1243; CrossRef (c) D. S. Feingold, G. Avigad, and S. Hestrin, J. Biol. Chem., 1957, 224, 295.
4. Chemical conversion from (+)-sucrose; (a) F. W. Lichtenthaler and S. Mondel, Carbohydr. Res., 1997, 303, 293. CrossRef
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7. D. Wagner, J. P. H. Verheyden, and J. G. Moffatt, J. Org. Chem., 1974, 39, 24. CrossRef
8. Conversion of 1,2-cis-pentofuranoside to 1,2-trans-pentofuranoside by the similar method, see A. Földesi, A. Trifonova, Z. Dinya, and J. Chattopadhyaya, J. Org. Chem., 2001, 66, 6560. CrossRef