合成步驟及數據

 General procedure for imidate formation (Method A) Step 1.

To a stirred solution of thio compound (1 equiv.) in acetone/H2O, 9/1 (0.1~0.2 M) was added NBS (4 or 6 equiv.) at rt. After being stirred for 2 h, the reaction was quenched by NaHCO3(aq.), Na2S2O3(aq.) and then removed acetone under reduced pressure. The mixture was diluted with CH2Cl2, washed by NaHCO3(aq.), Na2S2O3(aq.)

brine, dried over MgSO4 and then concentrated under reduced pressure. The residue was purified by column chromatography to give hemiacetal product.

Step 2.

To the hemiacetal product (1 equiv.) dissolved in anhydrous CH2Cl2 (0.05~0.2 M) was added Cl3CCN (6 equiv.), DBU (0.2 equiv.) at rt under N2 atmosphere. The reaction mixture was stirred for 2 h. The resulting mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography to give imidate glucuronide.

 General procedure for glucuronidation (Method B)

To the suspension of glucuronyl imidate (1.2 equiv.), benzyl oleanolate or allyl quillaic ester (1 equiv.) and active 4 Å molecular sieve powder in anhydrous CH2Cl2

(40~60 mM) was added B(PhF₅)₃ or TMSOTf (0.1 eq) at rt under N₂ atmosphere. After being stirred for 30 min, the reaction was quenched by Et3N and then filtered. The resulting mixture was concentrated under reduced pressure and purified by column chromatography.

Methyl

(trichloroacetimidoyl-2,3,4-tri-O-acetyl-α-D-glucopyranosid)uronate (25)⁷²

Compound 25 (150 mg, 95%) as white foam: R_f 0.28 (EtOAc/Hexanes, 1/3) was synthesized according to method A by using compound 70 (250 mg, 0.57 mmol) and purified by flash chromatography (silica gel, EtOAc/Hexanes, 1/3). 25: ¹H NMR (200 MHz, CDCl3) δ 8.72 (s, 1H, NH), 6.63 (d, J = 3.6 Hz, 1H, H-1), 5.62 (dd, J = 10.2, 9.4 Hz, 1H, H-4), 5.26 (dd, J = 10.1, 9.4 Hz, 1H, H-3), 5.14 (dd, J = 10.1, 3.6 Hz, 1H, H-2), 4.49 (d, J = 10.2 Hz, 1H, H-5), 3.74 (s, 3H, OCH3), 2.01 (s, 9H, OCOCH3*3) ppm.

Methyl

(trichloroacetimidoyl-2,3,4-tri-O-benzoyl-α-D-glucopyranosid)uronate (31)

Compound 31 (207 mg, 56%) as white foam: R_f 0.49 (EtOAc/Hexanes, 1/3) was synthesized according to method A by using 71 (348 mg, 0.55 mmol) and purified by flash chromatography (silica gel, EtOAc /Hexanes, 1/4). 31: ¹H NMR (200 MHz, CDCl3) δ 8.68 (s, 1H, NH), 7.99-7.86 (m, 6H, Ar-H), 7.55-7.31 (m, 9H, Ar-H), 6.91 (d, J = 3.5 Hz, 1H, H-1), 6.29 (dd, J = 10.2, 9.9 Hz, 1H, H-3), 5.75 (dd, J = 10.1, 9.9 Hz,

1H, H-4), 5.63 (dd, J = 10.2, 3.5 Hz, 1H, H-2), 4.76 (d, J = 10.1 Hz, 1H, H-5), 3.69 (s, 3H, OCH3) ppm; BBD ¹³C NMR (50 MHz, CDCl3) δ 167.4, 165.6, 165.4, 160.4, 133.8, 133.6, 130.0, 129.9, 128.6, 92.9 (C-1), 90.6, 71.1, 70.3, 69.7, 69.4, 53.2 ppm.

Methyl

(trichloroacetimidoyl-2,3,4-tri-O-pivaloyl-α-D-glucopyranosid)uronate (32)

Compound 32 (0.7 g, 56%) as white foam: R_f 0.41 (EtOAc/Hexanes, 1/10) was synthesized according to method A by using compound 72 (1.5 g, 2.65 mmol) and purified by flash chromatography (silica gel, EtOAc /Hexanes, 1/15). 32: ¹H NMR (400 MHz, CDCl3) δ 8.71 (s, 1H, NH), 6.65 (d, J = 3.3 Hz, 1H, H-1), 5.69 (dd, J = 10.1, 9.8 Hz, 1H, H-3), 5.30 (dd, J = 10.2, 9.8 Hz, 1H, H-4), 5.19 (dd, J = 10.1, 3.3 Hz, 1H, H-2), 4.48 (d, J = 10.2 Hz, 1H, H-5), 3.71 (s, 3H, OCH3), 1.15-1.10 (m, 27H, OCOC(CH3)3*3) ppm; BBD ¹³C NMR (100 MHz, CDCl3) δ 177.2 (OCOC(CH3)3), 176.9 (OCOC(CH3)3), 176.8 (OCOC(CH3)3), 167.4 (C-6), 160.5 (C=NH), 92.6 (C-1), 90.7 (CCl3), 70.8 (C-5), 69.5 (C-3), 68.8 (C-2), 68.7 (C-4), 53.1 (OCH3), 38.9 (OCOC(CH3)3), 38.8 (OCOC(CH3)3), 27.2 (OCOC(CH3)3), 27.1 (OCOC(CH3)3) ppm.

28-O-allyl quillate (61)

To a solution of quillaic acid (803 mg, 1.65 mmol) in THF/H₂O (10/1 v/v, 8 mL) was treated with allyl bromide (286 μL, 3.30 mmol), potassium carbonate (455 mg, 3.30 mmol) and TBAI (30 mg, 0.08 mmol) under rt. The mixture was heated at reflux for 3.5 h. The reaction mixture was concentrated under reduced pressure. The residue was then diluted with CH2Cl2, washed by H2O, dried over MgSO4 and concentrated to afford a crude residue which was purified by column chromatography (silica gel;

EtOAc/Hexanes, 1/3) to give compound 61 (797 mg, 92%) as white foam: Rf = 0.43 (EtOAc/Hexanes, 1/2); ¹H NMR (400 MHz, CDCl3) δ 9.35 (s, 1H. H-23), 5.87-5.78 (m, 1H, OCH2CHCH2), 5.36 (t, J = 3.4 Hz, 1H, H-12), 5.27 (d, J = 17.1 Hz, 1H, OCH2CHCH2), 5.18 (d, J = 10.4 Hz, 1H, OCH2CHCH2), 4.57-4.39 (m, 3H, H-16, OCH2CHCH2), 3.75 (dd, J = 11.3, 4.1 Hz, 1H, H-3), 3.03 (dd, J = 14.2, 3.5 Hz, 1H, H-18), 2.14 (t, J = 13.6 Hz, 1H, H-19), 2.08-1.82 (m, 5H), 1.81-1.56 (m, 7H), 1.55-1.40 (m, 2H), 1.38-1.28 (m, 4H), 1.28-1.20 (m, 2H), 1.17 (d, J = 8.7 Hz, 1H), 1.13-0.98 (m, 5H), 0.94-0.93 (m, 7H), 0.88 (s, 3H), 0.70 (s, 3H); BBD ¹³C NMR (100 MHz, CDCl3) δ 207.3, 176.4, 142.8, 132.0, 122.3, 118.0, 74.7, 71.7, 65.1, 55.2, 48.6, 48.0, 46.5, 46.3, 41.3, 40.5, 39.7, 38.0, 35.8, 35.3, 35.3, 32.7, 32.2, 30.7, 30.3, 26.7, 25.9, 24.5, 23.2, 20.6, 16.9, 15.6, 8.8 ppm; HRMS⁺ (ESI-TOF) calcd for C33H51O5 [M+H]⁺ 527.3731, found 527.3733.

28-O-Allyl-3-O-(methyl 2,3,4-tri-O-pivaloyl-β-D-glucopyranosiduronate)quillate (66)

Compound 66 (16.5 mg, 60%) as a white solid: R_f 0.40 (EtOAc/Hexanes, 1/4) was synthesized according to method B by using 32 (20 mg, 0.033 mmol), 61 (15 mg, 0.028 mmol) and TMSOTf (0.5 μL, 0.0028 mmol); ¹H NMR (600 MHz, CDCl3) δ 9.40 (s, 1H, H-23), 5.88-5.82 (m, 1H, OCH2CHCH2), 5.38 (t, J = 3.4 Hz, 1H, H-12), 5.31-5.16 (m, 4H, OCH2CHCH2, H-3′, H-4′), 5.10 (t, J = 8.8, 8.2 Hz, 1H, H-2′), 4.52-4.47 (m, 4H, H-1′, OCH2CHCH2, H-16), 3.99 (d, J = 10.0, 1H, H-5′), 3.84 (dd, J = 11.7, 4.62 Hz, 1H, H-3), 3.72 (s, 3H, OCH3), 3.06 (dd, J = 14.3, 4.1 Hz, 1H, H-18), 2.14 (t, J = 13.6 Hz, 1H, H-19), 1.89-1.87 (m, 4H), 1.79-1.73 (m, 5H), 1.67-1.62 (m, 4H), 1.48-1.39 (m, 2H), 1.33-1.29 (m, 4H), 1.16-1.08 (m, 30H), 1.04-0.99 (m, 3H), 0.96 (s, 3H), 0.94 (s, 3H), 0.90 (s, 3H), 0.86 (m, 1H), 0.70 (s, 3H) ppm; BBD ¹³C NMR (150 MHz, CDCl3) δ 207.5 (C-23), 177.1, 176.6, 176.5, 167.5 (C-6′), 142.9, 132.3 (OCH2CHCH2), 122.7 (C-12), 118.3 (OCH2CHCH2), 100.8 (C-1′), 81.3 (C-3), 75.0 (C-16), 72.5 (C-5′), 72.1 (C-3′), 71.4 (C-2′), 69.7 (C-4′), 65.3 (allylic CH2), 54.6, 52.9, 49.2, 48.9, 46.7, 46.5, 41.5, 40.8, 39.9, 38.9, 38.8, 38.2, 36.1, 35.6, 35.6, 32.9, 32.4, 30.9, 30.5, 29.8, 27.3, 27.3, 27.2, 27.1, 24.9, 24.7, 23.4, 20.2, 17.2, 15.8, 10.4 ppm; HRMS⁺ (ESI-TOF) calcd for C55H85O14 [M+H]⁺ 969.5934, found 969.5904.

28-O-benzyl oleanolate(67)⁷³

To a stirred solution of oleanolic acid (10.0 g, 21.9 mmol), K₂CO₃ (4.55 g, 32.9 mmol) and TBAI (81.0 mg, 0.219 mmol) in aqueous THF (100 mL) was added benzyl chloride (3.8 mL, 32.9 mmol) at rt. The reaction was heated at reflux and stirred 12 h.

The resulting mixture was concentrated under reduced pressure, the residue was diluted with CH2Cl2, washed by water and brine, dried over MgSO4 and then concentrated. The residue was recrystallized for methanol to obtain 67 (10.16 g, 84%) as a white crystal;

1H NMR (200 MHz, CDCl3) δ 7.40-7.29 (m, 5H, Ar-H), 5.28 (t, J = 3.4 Hz, 1H, H-12), 5.08-5.05 (m, 2H, CO2CH2Ph), 3.28-3.12 (m, 1H, H-3), 2.88 (dd, 1H, H-18), 2.02-1.80 (m, 3H), 1.75-1.57 (m, 6H), 1.54-1.45 (m, 3H), 1.45-1.15 (m, 8H), 1.12 (s, 3H), 1.05-0.98 (m, 2H), 0.97 (s, 3H), 0.91 (s, 3H), 0.89 (s, 3H), 0.87 (s, 3H), 0.77 (s, 3H), 0.73 (s, 1H, H-5), 0.60 (s, 3H) ppm; BBD ¹³C NMR (50 MHz, CDCl3) δ 177.6, 143.8, 136.5, 128.5, 128.1, 122.6, 79.16 (C-3), 66.1, 55.3, 47.7, 46.8, 46.0, 41.8, 41.5, 39.4, 38.8, 38.6, 34.0, 33.3, 32.9, 32.5, 30.8, 27.7, 27.3, 26.0, 23.7, 23.5, 23.2, 18.5, 17.0, 15.7, 15.4 ppm; HRMS⁺ (ESI-TOF) calcd for C37H55O3 [M+H]⁺ 547.4146, found 547.4140.

Methyl 1,2,3,4-tetra-O-acetyl-α-D-glucopyranosiduronate (69)⁷⁴

Glucuronolactone (11 g, 62.4 mmol) in methanol (70 mL) was added NaOH (0.25 g, 6.24 mmol) and the reaction mixture was stirred for 5 h. The resulting mixture was concentrated by rotavapor to give a residue which was added pyridine (80 mL) and then slowly added AcOH (50 mL) at 0 ℃. The reaction mixture was stirred for 12 h, and then was concentrated, purified by column chromatography (silica gel, EtOAc/Hexanes, 1/2 to 1/1) to give compound 69 (19 g, 81%) as yellow foam: R_f 0.53 (EtOAc/Hexanes, 1/1); α-anomer: ¹H NMR (200 MHz, CDCl3) δ 6.39 (d, J = 3.6 Hz, 1H, H-1), 5.50 (dd, J

= 10.2, 9.4 Hz, 1H, H-4), 5.21 (dd, J = 10.1, 9.4 Hz, 1H, H-3), 5.11 (dd, J = 10.1, 3.6 Hz, 1H, H-2), 4.41 (d, J = 10.2 Hz, 1H, H-5), 3.74 (s, 3H, OCH3), 2.18 (s, 3H, OCOCH3), 2.03 (s, 6H, OCOCH3), 2.01 (s, 3H, OCOCH3*2) ppm.

Methyl p-tolyl 2,3,4-tri-O-acetyl-1-thio-β-D-glucopyranosiduronate (70)⁷⁵

To a stirred solution of compound 69 (13.8 g, 36.6 mmol) in anhydrous CH2Cl2 (40 mL) was added 33% HBr/HOAc (40 mL) in ice bath under N2 atmosphere. Upon completion of the reaction after 6 h, the reaction was quenched by ice water and then it was diluted with CH2Cl2, washed by ice water, H2O, brine, dried over MgSO4 and then concentrated to afford crude glucuronyl bromide. To a stirred solution of the glucuronyl bromide (14.6 g, 36.8 mmol) in 1.0 M Na2CO3(aq.) (40 mL)/EA (40 mL) was added HSTol (9.1 g, 73.5 mmol) then TBAI (2.72 g, 7.35 mmol) at rt. After being stirred for 12 h, the reaction was quenched by saturated NaHCO3 and then was diluted with EA, washed by saturated NaHCO3, brine, dried over MgSO4 and then concentrated. The residue was purified by column chromatography (silica gel, EtOAc/Hexanes, 1/5 to 1/2) to give compound 70 (12.1 g, 75%) as a white solid: Rf 0.38 (EtOAc/Hexanes, 1/3); ¹H NMR (200 MHz, CDCl3) δ 7.37 (d, J = 8.0 Hz, 2H, Ar-H), 7.11 (d, J = 8.0 Hz, 2H, Ar-H), 5.23 (dd, J = 9.5, 8.6 Hz, 1H, H-3), 5.11 (dd, J = 9.6, 9.5 Hz, 1H, H-4), 4.89 (dd, J = 8.6, 10.0 Hz, 1H, H-2), 4.64 (d, J = 10.0 Hz, 1H, H-1), 3.99 (d, J = 9.6 Hz, 1H, H-5), 3.73 (s, 3H, OCH3), 2.32 (s, 3H, SPhCH3), 2.06 (s, 3H, OCOCH3), 1.97 (s, 6H, OCOCH₃*2) ppm.

Methyl (p-tolyl 2,3,4-tri-O-benzoyl-1-thio-β-D-glucopyranosid)uronate (71)

To a stirred suspension of compound 70 (177 mg, 0.404 mmol) in MeOH (5 mL) was added Na (1 mg, 0.0404 mmol) at rt. Upon completion of the reaction after 3 h, the reaction was quenched by amberlite H+. The reaction mixture was filtered and concentrated. The residue was added anhydrous CH2Cl2 and then added BzCl (0.281 mL, 2.42 mmol), TEA (0.563 mL, 4.04 mmol) and DMAP (4.94 mg, 0.0404 mmol) in ice bath under N2 atmosphere. After being stirred for 6 h, the reaction was quenched by saturated NH4Cl and then it was diluted with CH2Cl2, washed by H2O, saturated brine, dried over MgSO4 and then concentrated under reduced pressure. The residue was purified by column chromatography (silica gel; EtOAc/Hexanes, 1/5) to afford compound 71 (220 mg, 87%) as white solid : R_f 0.33 (EtOAc/Hexanes, 1/4); ¹H NMR (400 MHz, CDCl3) δ 7.97-7.80 (m, 6H, Ar-H), 7.55-7.13 (m, 13H, Ar-H), 5.89 (dd, J = 9.6, 9.3 Hz, 1H, H-3), 5.60 (dd, J = 9.7, 9.6 Hz, 1H, H-4), 5.45 (dd, J = 9.6, 9.3 Hz, 1H, H-2), 4.98 (d, J = 9.8 Hz, 1H, H-1), 4.33 (d, J = 9.7 Hz, 1H, H-5), 3.71 (s, 3H, OCH3), 2.36 (s, 3H, SPhCH3) ppm; BBD ¹³C NMR (100 MHz, CDCl3) δ 167.2, 165.3, 139.2, 134.3, 133.5, 130.0, 129.9, 128.6, 128.4, 86.7 (C-1), 76.6, 73.6, 70.2, 53.1, 21.4 ppm;

HRMS⁺ (ESI-TOF) calcd for C₃₅H₃₁O₉S [M+H]⁺ 627.1683, found 627.1688.

Methyl (p-tolyl 2,3,4-tri-O-pivaloyl-1-thio-β-D-glucopyranosid)uronate (72)

To a stirred suspension of 70 (4.57 g, 10.3 mmol) in MeOH (15 mL) was added Na (23.6 mg, 1.03 mmol) at rt. Upon completion of the reaction after 3 h, the reaction was quenched by Amberlyst IR120 (H⁺). The reaction mixture was filtered and concentrated.

The residue (1.0 g, 3.2 mmol) was added anhydrous CH2Cl2 (10 mL) and then added PivCl (2.4 mL, 19.1 mmol), TEA (4.4 mL, 32 mmol) and DMAP (39.1 mg, 0.32 mmol) in ice bath under N2 atmosphere. After being stirred for 6 h, the reaction was quenched by NH4Cl and then it was diluted with CH2Cl2, washed by H2O, brine, dried over MgSO4 and then concentrated under reduced pressure. The residue was purified by column chromatography (silica gel; EtOAc/Hexanes, 1/8) to afford 72 (1.5 g, 83%) as white solid: Rf 0.72 (EtOAc/Hexanes, 1/2); ¹H NMR (200 MHz, CDCl3) δ 7.37 (d, 2H, Ar-H), 7.13 (d, 2H, Ar-H), 5.36 (dd, J = 9.3, 9.1 Hz, 1H, H-3), 5.19 (dd, J = 9.8, 9.3 Hz, 1H, H-4), 5.02 (dd, J = 10.1, 9.1 Hz, 1H, H-2), 4.67 (d, J = 10.1 Hz, 1H, H-1), 4.05 (d, J

= 9.8 Hz, 1H, H-5), 3.74 (s, 3H, OCH3), 2.35 (s, 3H, SPhCH3), 1.03-1.00 (m, 27H, OCOC(CH3)3) ppm; BBD ¹³C NMR (50 MHz, CDCl3) δ 176.8 (OCOC(CH3)3), 176.3 (OCOC(CH3)3), 176.1 (OCOC(CH3)3), 166.9 (C-6), 138.7 (Ar-C), 133.6 (Ar-C), 129.7 (Ar-C), 127.6 (Ar-C), 86.7 (C-1), 76.2 (C-5), 72.6 (C-3), 69.0 (C-2), 68.9 (C-4), 52.6 (OCH3), 38.6 (OCOC(CH3)3), 27.0 (OCOC(CH3)3), 21.1 (SPhCH3) ppm; HRMS⁺ (ESI-TOF) calcd for C₂₉H₄₃O₉S [M+H]⁺ 567.2622, found 567.2609.

Methyl

(p-tolyl 2,3,4-tri-O-tert-butyldimethylsilyl-1-thio-β-D-glucopyranosid)uronate (74) To a stirred suspension of 70 (4.57 g, 10.3 mmol) in MeOH (15 mL) was added Na (23.6 mg, 1.03 mmol) at rt. Upon completion of the reaction after 3 h, the reaction was quenched by amberlite H+. The reaction mixture was filtered and concentrated. The residue (1 g, 3.18 mmol) was added anhydrous DMF (5 mL) and then added TBSCl (2.88 g, 19.1 mmol), imidazole (0.78 g, 11.5 mmol) at rt under N2 atmosphere. The mixture was heated to 80℃. After being stirred for 12 h, the reaction was quenched by H2O, concentrated and then it was diluted with CH2Cl2, washed by H2O, brine, dried over MgSO4 and then concentrated under reduced pressure. The residue was purified by column chromatography (silica gel; EtOAc/Hexanes, 1/20) to afford 74 (0.7 g, 32%) as a colorless syrup: Rf 0.72 (EtOAc/Hexanes, 1/6); ¹H NMR (200 MHz, CDCl3) δ 7.45 (d,

Methyl

(trichloroacetimidoyl-2,3,4-tri-O-tert-butyldimethylsilyl-α-D-glucopyranosid)urona te (79)

Compound 79 (25 mg, 54%) as a colorless syrup: Rf 0.59 (EtOAc/Hexanes, 1/10) was synthesized according to method A by using compound 74 (43.8 mg, 0.067 mmol) and purified by flash chromatography (silica gel, EtOAc/Hexanes, 1/30 to 1/20). 79: ¹H NMR (200 MHz, CDCl₃) δ 7.26 (s, 1H, NH), 5.56 (s, 1H, H-1), 4.47 (s, 1H), 4.10 (s, 1H), 3.98 (s, 1H), 3.73 (s, 3H, CO2CH3), 3.39 (s, 1H), 0.95 (m, 3H), 0.94 (s, 6H), 0.92 (s, 3H), 0.91 (s, 6H), 0.86 (s, 3H), 0.85 (s, 6H), 0.21 (s, 3H), 0.20 (s, 3H), 0.14 (s, 3H), 0.13 (s, 3H), 0.06 (s, 3H), 0.05 (s, 3H) ppm; ¹³C NMR (50 MHz, CDCl3) δ 170.0 (CO₂CH₃), 169.0 (C=NH), 90.3 (C-1), 77.4, 76.9, 71.7, 71.2, 52.1 (CO₂CH₃), 26.1 (Si(CH3)2C(CH3)3), 25.9 (Si(CH3)2C(CH3)3), 25.7 (Si(CH3)2C(CH3)3), 18.4 (Si(CH₃)₂C(CH₃)₃), 18.2 (Si(CH₃)₂C(CH₃)₃), 18.0 (Si(CH₃)₂C(CH₃)₃), -4.0 (Si(CH3)2C(CH3)3), -4.8 (Si(CH3)2C(CH3)3), -5.1 (Si(CH3)2C(CH3)3) ppm.

p-tolyl 4,6-O-benzylidene-3-O-benzyl-1-thio-β-D-glucopyranoside (84) ⁷⁶

To a stirred solution of 83 (7.03 g, 18.7 mmol) in anhydrous ACN (20 mL) was added dimethoxy-methylbenzene (5.46 mL, 37.3 mmol), TsOH (0.362 mg, 1.87 mmol) at rt under N2 atmosphere. Upon completion of the reaction after 1 h, the reaction was quenched by TEA. The reaction mixture was concentrated under reduced pressure and recrystallized by ether to give 84 (6.85 g, 79%) as a white solid: Rf 0.38 (EtOAc /Hexanes, 1/4); ¹H NMR (200 MHz, CDCl3) δ 7.48-7.28 (m, 12H, Ar-H), 7.16-7.10 (m, 3H, Ar-H), 5.56 (s, 1H, CHPh), 4.85 (dd, J = 32.8, 21.3 Hz, 2H, OCH2Ph), 4.56 (d, J = 9.5 Hz, 1H, H-1), 4.38 (dd, J = 10.4, 4.7 Hz, 1H, H-4), 3.78 (dd, J = 8.6, 10.4 Hz, 1H, H-3), 3.58-3.43 (m, 4H, H-2, H-5), 3.50 (dt, J = 6.6, 4.6, 2.2 Hz, 2H, H-6), 2.55 (d, J = 2.2 Hz, 1H, OH), 2.35 (s, 3H, SPhCH3) ppm.

p-tolyl 2-O-benzoyl-4,6-O-benzylidene-3-O-benzyl-1-thio-β-D-glucopyranoside (85)⁷⁶

To a stirred solution of 84 (7.4 g, 15.9 mmol) in anhydrous CH₂Cl₂ (30 mL) was added BzCl (2.8 mL, 23.9 mmol), TEA (3.3 mL, 23.9 mmol), DMAP (0.39 g, 3.18 mmol) at 0 ℃ under N2 atmosphere. After being stirred for 8 h, the reaction was quenched by NH4Cl and then diluted with CH2Cl2, washed by H2O, brine, dried by MgSO4. Collected organic layer and then concentrated under reduced pressure. The residue was recrystallized by ether to give 85 (7.8 g, 86%) as a white solid: Rf 0.56 (EtOAc/Hexanes, 1/4); ¹H NMR (200 MHz, CDCl3) δ 8.02 (d, J = 1.2 Hz, 2H, Ar-H), 7.65-7.31 (m, 10H, Ar-H), 7.12-7.08 (m, 6H, Ar-H), 5.60 (s, 1H, CHPh), 5.25 (dd, J = 10.0, 8.4 Hz, 1H, H-2), 4.76 (d, J = 10.0 Hz, 1H, H-1), 4.74 (dd, J = 32.8, 21.3 Hz, 2H, OCH2Ph), 4.42 (dd, J = 10.4, 4.8 Hz, 1H, H-4), 3.92-3.75 (m, 3H, H-3, H-6), 3.54 (dt, J

= 10.2, 4.8 Hz, 1H, H-5), 2.35 (s, 3H, SPhCH3) ppm.

2-O-benzoyl-3,4-di-O-benzyl-1-thio-β-D-glucopyranoside (86)⁷⁷

To a stirred solution of 85 (1 g, 1.76 mmol) in anhydrous BH3‧THF (8.8 mL, 8.79 mmol), CH2Cl2 (5 mL) was added TMSOTf (32 μL, 0.176 mmol) at 0 ℃ under N2

atmosphere. After being stirred for 5 h, the reaction was quenched by TEA, MeOH and then concentrated under reduced pressure. The residue was recrystallized (silica gel, EtOAc/Hexanes, 1/6) by ether to give 86 (0.93 g, 92%) as a white solid: Rf 0.23 (EtOAc/Hexanes, 1/4); ¹H NMR (200 MHz, CDCl3) δ 8.06 (d, J = 1.2 Hz, 2H, Ar-H), 7.63-7.29 (m, 10H, Ar-H), 7.16-7.07 (m, 7H, Ar-H), 5.23 (dd, J = 10.0, 9.0 Hz, 1H, H-2), 4.87-4.61 (m, 5H, OCH2Ph*2, H-1), 4.00-3.46 (m, 2H, H-6), 3.85 (dd, J = 9.0, 8.9 Hz, 1H, H-3), 3.45 (dd, J = 9.5, 8.9 Hz, 1H, H-4), 3.47 (ddd, J = 9.5, 4.6, 2.6 Hz, 1H, H-5), 2.32 (s, 3H, SPhCH3) ppm; BBD ¹³C NMR (50 MHz, CDCl3) δ 165.3, 138.6, 137.8, 137.7, 133.4, 130.0, 129.9, 128.7, 128.6, 128.4, 128.2, 127.8, 86.4 (C-1), 84.1, 79.7, 75.5, 75.3, 72.6, 62.2, 21.3 ppm; HRMS⁺ (ESI-TOF) calcd for C34H35O6S [M+H]⁺ 571.2149, found 571.2136.

2-O-benzoyl-3,4-di-O-benzyl-1-thio-β-D-glucopyranosyluronate (87)

To a stirred solution of compound 86 (54.2 mg, 0.095 mmol) in CH2Cl2/H2O, 2/1 (1.5 mL) was added TEMPO (1.48 mg, 0.0095 mmol), BAIB (45.9 mg, 0.14 mmol) at rt.

After being stirred for 12 h, the reaction was quenched by Na2S2O3 and then diluted with CH2Cl2, washed by NaHCO3, Na2S2O3, brine, removed H2O by MgSO4. Collected organic layer and then concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, EtOAc/CH₂Cl₂/Hexanes, 1/1/3) to give 87 (46 mg, 83%) as a white solid: Rf 0.13 (EtOAc/Hexanes, 1/1); ¹H NMR (200 MHz, CDCl3) δ 7.99 (d, J = 1.2 Hz, 2H, Ar-H), 7.65-7.31 (m, 10H, Ar-H), 7.13-7.10 (m, 7H, Ar-H), 5.27 (dd, J = 9.0, 7.1 Hz, 1H, H-2), 4.90 (d, J = 9.0 Hz, 1H, H-1), 4.66 (dd, 2H, OCH2Ph), 4.17 (d, J = 7.5 Hz, 1H, H-5), 3.93 (dd, J = 7.8, 7.5 Hz, 1H, H-4), 3.82 (d, J = 7.1 Hz, 1H, H-3), 2.30 (s, 3H, SPhCH3) ppm; BBD ¹³C NMR (50 MHz, CDCl3) δ 170.5, 165.2, 138.8, 137.4, 133.6, 130.0, 128.6, 128.4, 128.3, 128.1, 127.9, 86.3 (C-1), 81.8, 78.7, 74.8, 71.8, 21.3 ppm; HRMS⁺ (ESI-TOF) calcd for C34H32O7SNa [M+Na]⁺ 607.1761, found 607.1762.

Methyl (2-O-benzoyl-3,4-di-O-benzyl-1-thio-β-D-glucopyranosid)uronate (88) To a stirred solution of 87 (34 mg, 0.058 mmol) in DMF (1 mL) was added K2CO3 (4 mg, 0.029 mmol), MeI (6 μL, 0.087 mmol) at rt. The reaction was heated to 80 ℃, after being stirred for 12 h, the reaction was quenched by NH4Cl and then diluted with CH2Cl2, washed by H2O, brine, dried by MgSO4. Collect organic layer and then concentrate under reduced pressure. The residue was purified by column chromatography (silica gel, EtOAc/Hexanes, 1/4) to give 88 (28 mg, 81%) as a white solid: Rf 0.58 (EtOAc/Hexanes, 1/2); ¹H NMR (200 MHz, CDCl3) δ 8.00 (d, J = 1.2 Hz, 2H, Ar-H), 7.65-7.31 (m, 10H, Ar-H), 7.14-7.06 (m, 7H, Ar-H), 5.23 (dd, J = 10.0, 8.6 Hz, 1H, H-2), 4.74 (d, J = 10.0 Hz, 1H, H-1), 4.70 (dd, 4H, OCH2Ph), 4.03-3.82 (m, 3H, H-3, H-4, H-5), 3.76 (s, 3H, OCH3), 2.30 (s, 3H, SPhCH3) ppm; BBD ¹³C NMR (50 MHz, CDCl3) δ 168.5, 165.1, 138.6, 137.7, 137.5, 133.6, 133.4, 130.0, 129.8, 128.6, 128.4, 128.2, 127.9, 87.4 (C-1), 83.4, 79.3, 78.3, 75.4, 75.3, 52.7, 21.3 ppm; HRMS⁺ (ESI-TOF) calcd for C35H34O7SNa [M+Na]⁺ 621.1917, found 621.1926.

Methyl

(trichloroacetimidoyl-2-O-benzoyl-3,4-O-benzyl-α-D-glucopyranosid)uronate (90) Compound 90 (27 mg, 60%) as a white foam: R_f 0.45 (EtOAc/Hexanes, 1/3) was synthesized according to method A by using compound 88 (27 mg, 0.055 mmol), Cl3CCN (34 μL, 0.33 mmol), DBU (1.5 μL, 0.011 mmol) and was purified by column chromatography (silica gel, EtOAc/Hexanes, 1/5). 90: ¹H NMR (200 MHz, CDCl3) δ 8.56 (s, 1H, NH), 7.94 (d, J = 1.2 Hz, 2H, Ar-H), 7.58-7.27 (m, 7H, Ar-H), 7.18 (s, 6H, Ar-H), 6.64 (d, J = 3.5 Hz, 1H, H-1), 5.39 (dd, J = 9.9, 3.5 Hz, 1H, H-2), 4.86-4.63 (m, 4H, OCH2Ph*2), 4.48 (d, J = 10.4 Hz, 1H, H-5), 4.27 (dd, J = 10.4, 9.3 Hz, 1H, H-4), 4.01 (dd, J = 9.9, 9.3 Hz, 1H, H-3), 3.74 (s, 3H, OCH3) ppm; BBD ¹³C NMR (50 MHz, CDCl3) δ 168.8, 165.5, 160.5, 137.5, 133.6, 129.9, 129.2, 128.7, 128.6, 128.4, 128.2, 127.9, 93.7 (C-1), 79.2, 78.8, 77.4, 75.7, 72.8, 72.2, 52.9 ppm.

28-O-benzyl-3-O-(methyl 2,3,4-tri-O-benzoyl–β–D-glucopyranosyluronate) oleanolate (91)

Compound 91 (30 mg, 52%) as a white solid: R_f 0.56 (EtOAc/CH₂Cl₂/Hexanes, 1/1/4) was synthesized according to method B by using 31 (46 mg, 0.082 mmol), 67 (30 mg, 0.055 mmol) and B(PhF5)3 (3 mg, 0.0055 mmol) and purified by flash chromatography (silica gel, EtOAc/CH2Cl2/Hexanes, 1/1/15 to 1/1/10). 91: ¹H NMR (200 MHz, CDCl3) δ 7.95-7.82 (m, 6H, Ar-H), 7.52-7.29 (m, 14H, Ar-H), 5.90 (dd, J = 9.8, 9.6 Hz, 1H, H-3′), 5.69-5.54 (m, 2H, H-2′, H-4′), 5.27 (t, J = 3.4 Hz, 1H, H-12), 5.07-5.04 (m, 2H, CO2CH2Ph), 4.88 (d, J = 7.7 Hz, 1H, H-1′), 4.30 (d, J = 9.7 Hz, 1H, H-5′), 3.69 (s, 3H, OCH3), 3.13-3.10 (m, 1H, H-3), 2.92-2.83 (m, 1H, H-18), 2.00-1.75 (m, 5H), 1.73-1.62 (m, 4H), 1.54-1.45 (m, 2H), 1.34-1.13 (m, 8H), 1.08 (s, 3H), 1.03-1.00 (m, 1H), 0.98-0.93 (m, 1H), 0.91 (s, 3H), 0.89 (s, 3H), 0.84 (s, 3H), 0.69 (s, 3H), 0.66 (s, 1H, H-5), 0.61 (s, 3H), 0.55 (s, 3H) ppm; BBD ¹³C NMR (50 MHz, CDCl3) δ 177.6, 167.5, 165.9, 165.3, 165.0, 143.8, 136.5, 133.5, 133.3, 129.9, 128.5, 128.4, 128.1, 122.7, 103.4 (C-1′), 90.9 (C-3), 72.9 (C-5′), 72.5 (C-2′), 71.9 (C-4′), 70.6 (C-3′), 66.1, 55.5, 53.0, 47.7, 46.8, 45.9, 41.8, 41.5, 39.4, 38.9, 38.5, 36.8, 33.9, 33.2, 32.8, 32.5, 30.8, 27.8, 25.9, 23.8, 23.5, 23.1, 18.2, 16.9, 16.3, 15.3 ppm; HRMS⁺ (ESI-TOF) calcd for C65H77O12 [M+H]⁺ 1049.5410, found 1049.5411.

3-O-β-D-glucopyranosyloxyuronate quillaic acid (92)

To a stirred solution of 91 (30 mg, 0.029 mmol) in MeOH/THF, 2/3 (3 mL) was added Pd/C (3 mg,), TsOH (0.362 mg, 10% w/w) at rt under H2 atmosphere (balloon).

Upon completion of the reaction after 5 h, the reaction mixture was filtered, concentrated under reduced pressure and purified by column chromatography. The resulting compound then dissolved in KOH/THF, 1/4 (5 mL) at rt. The reaction was heated to 66 ℃ reflux. After being stirred for 12 h, the reaction was quenched by Amberlyst IR120 (H⁺), concentrated under reduced pressure and purified by HPLC to give 92 (10 mg, 52%) as a white solid: R_f 0. 20 (CH₂Cl₂/MeOH, 5/1). The HPLC column used in the purification was Ascentis-RP18 (5 μm, 250 mm × 10 mm). Solution A: ddH₂O. Solution B: ACN. Mobile phase: see Table 3. The flow rate was 2 mL/min.

Peaks were detected at 210 nm.; ¹H NMR (600 MHz, CD3OD) δ 5.24 (t, J = 3.4 Hz, 1H,

28-O-benzyl-3-O-(methyl 2,3,4-tri-O-acetyl–β–D-glucopyranosyluronate) oleanolate (94)

Compound 94 (30 mg, 52%) as a white solid: R_f 0.56 (EtOAc/CH₂Cl₂/Hexanes, 1/1/4) was synthesized according to method B by using compound 25 (46 mg, 0.082 mmol), 67 (30 mg, 0.055 mmol) and B(PhF₅)₃ (3 mg, 0.0055 mmol) and purified by flash chromatography (silica gel, EtOAc/CH2Cl2/Hexanes, 1/1/10 to 1/1/6). 94: ¹H NMR (200 MHz, CDCl3) δ 7.40-7.29 (m, 5H, Ar-H), 5.27 (t, J = 3.4 Hz, 1H, H-12), 5.25-5.08 (m, 3H, H-2′, H-3′, H-4′), 5.07-5.04 (m, 2H, CO2CH2Ph), 4.58 (d, J = 7.8 Hz, 1H, H-1′), 4.00 (d, J = 9.5 Hz, 1H, H-5′), 3.74 (s, 3H, OCH3), 3.13-3.05 (m, 1H, H-3), 2.95-2.86 (m, 1H, H-18), 2.02-2.00 (m, 9H, OCOCH3*3), 2.00-1.75 (m, 5H), 1.73-1.62 (m, 2H), 1.54-1.45 (m, 3H), 1.43-1.30 (m, 4H), 1.29-1.13 (m, 5H), 1.08 (s, 3H), 0.98-0.93 (m, 2H), 0.91 (s, 6H), 0.90 (s, 3H), 0.86 (s, 3H), 0.72 (s, 3H),0.66 (s, 1H, H-5), 0.58 (s, 3H) ppm; BBD ¹³C NMR (50 MHz, CDCl3) δ 177.6, 170.4, 169.6, 169.3, 167.4, 143.8, 136.5, 128.5, 128.1, 122.6, 103.1 (C-1′), 90.8, 72.6, 72.3, 71.6, 69.7, 66.1, 55.6, 53.0, 47.7, 46.8, 46.0, 41.8, 41.5, 39.4, 39.0, 38.5, 36.8, 33.9, 33.2, 32.8, 32.5, 30.8, 27.8, 25.9, 25.8, 23.8, 23.5, 23.2, 20.8, 18.3, 16.9, 16.5 ppm; HRMS⁺ (ESI-TOF) calcd for C₅₀H₇₁O₁₂ [M+H]⁺ 863.4940, found 863.4931.

28-O-benzyl-3-O-(methyl 2,3,4-tri-O-pivaloyl–β–D-glucopyranosiduronate) oleanolate (95)

Compound 95 (13 mg, 48%) as white solid: R_f 0.77 (EtOAc/CH₂Cl₂/Hexanes, 1/1/4) was synthesized according to method B by using compound 32 (20 mg, 0.033 mmol), 67 (15 mg, 0.028 mmol) and B(PhF₅)₃ (1.5 mg, 0.0028 mmol) and purified by flash chromatography (silica gel, EtOAc/CH2Cl2/Hexanes, 1/1/15 to 1/1/10). 95: ¹H NMR (400 MHz, CDCl3) δ 7.35-7.29 (m, 5H, Ar-H), 5.35 (dd, J = 9.4, 9.0 Hz, 1H, H-3′), 5.27 (t, J = 3.4 Hz, 1H, H-12), 5.22 (dd, J = 10.0, 9.4 Hz, 1H, H-4′), 5.14-5.01 (m, 3H, H-2′, OCH2Ph), 4.64 (d, 1H, H-1′), 4.02 (d, J = 10.0 Hz, 1H, H-5′), 3.71 (s, 3H, OCH3), 3.11-3.07 (m, 1H, H-3), 2.91-2.87 (m, 1H, H-18), 2.00-1.93 (m, 1H), 1.83-1.74 (m, 3H), 1.70-1.62 (m, 4H), 1.54-1.48 (m, 2H), 1.47-1.20 (m, 8H), 1.18-1.10 (m, 33H), 1.03-1.00 (m, 1H), 0.91 (s, 3H), 0.90 (s, 3H), 0.89 (s, 3H), 0.85 (s, 3H), 0.72 (s, 3H), 0.68 (s, 1H, H-5), 0.58 (s, 3H) ppm; BBD ¹³C NMR (100 MHz, CDCl3) δ 177.5, 177.2, 176.7, 176.4, 167.6, 143.7, 136.5, 128.5, 128.1, 122.6, 102.5 (C-1′), 89.4, 72.7 (C-5′), 72.3 (C-3′), 71.8 (C-2′), 69.9 (C-4′), 66.1, 55.8, 52.8, 47.7, 46.9, 46.0, 41.8, 41.5, 39.4, 39.1, 38.9, 38.6, 36.8, 34.0, 33.3, 32.8, 32.5, 30.8, 28.4, 27.7, 27.6, 27.3, 27.2, 26.0, 25.8, 23.8, 23.5, 23.2, 18.3, 16.9, 16.4, 15.4 ppm; HRMS⁺ (ESI-TOF) calcd for C59H89O12 [M+H]⁺ 989.6349, found 989.6352.

28-O-benzyl-3-O-(methyl

2,3,4-tri-O-tert-butyldimethylsilyl-β-D-glucopyranosiduronate) oleanolate (96) Compound 96 (16 mg, 63%) was synthesized according to method B by using compound 79 (20 mg, 0.029 mmol), 67 (13 mg, 0.024 mmol) and B(PhF5)3 (1.5 mg, 0.0029 mmol). The purification of compound 96 was under flash column chromatography (silica gel, EtOAc/CH2Cl2/Hexanes, 1/1/15 to 1/1/10). 96: ¹H NMR (200 MHz, CDCl3) δ 7.40-7.29 (m, 5H, Ar-H), 5.28 (t, J = 3.4 Hz, 1H, H-12), 5.13-4.99 (m, 2H, CO2CH2Ph), 4.84 (d, J = 5.76 Hz, 1H, H-1′), 4.25 (m, 2H), 3.75-3.68 (m, 5H, OCH3), 3.11-3.02 (m, 1H, H-3), 2.92-2.85 (d, 1H, H-18), 2.02-1.80 (m, 5H), 1.75-1.57 (m, 4H), 1.54-1.45 (m, 3H), 1.45-1.15 (m, 9H), 1.11 (s, 3H), 0.94 (s, 3H), 0.92 (s, 3H), 0.91 (s, 3H), 0.89 (s, 9H), 0.88 (s, 9H), 0.87 (s, 9H), 0.85 (s, 3H), 0.80 (s, 3H), 0.73 (s, 1H, H-5), 0.60 (s, 3H), 0.10 (s, 6H), 0.09 (s, 6H), 0.07 (s, 3H), 0.05 (s, 3H) ppm; BBD

13C NMR (50 MHz, CDCl3) δ 177.6, 170.8, 143.7, 136.6, 128.5, 128.1, 122.8, 103.9 (C-1′), 88.7, 79.0, 73.0, 71.7, 66.1, 55.9, 52.1, 47.8, 46.9, 46.0, 41.8, 41.5, 39.5, 39.2, 38.9, 36.9, 34.0, 33.3, 32.9, 32.5, 30.9, 28.2, 27.8, 26.0, 23.8, 23.5, 23.2, 18.3, 18.0, 17.0, 16.7, 15.5, -3.9, -4.1, -4.8 ppm; HRMS⁺ (ESI-TOF) calcd for C62H107O9Si3

[M+H]⁺ 1079.7217, found 1079.7223.

28-O-benzyl-3-O-(methyl-2-O-benzoyl-3,4-di-O-benzyl-β-D-glucopyranosyluronate) oleanolate (97)

Compound 97 (9.5 mg, 50%) as a white solid: R_f 0.55 (EtOAc/Hexanes, 1/3) was synthesized according to method B by using compound 90 (14 mg, 0.022 mmol), 67 (10 mg, 0.018 mmol) and B(PhF5)3 (1.0 mg, 0.0022 mmol). The purification of compound 97 was under flash column chromatography (silica gel, EtOAc/Hexanes, 1/15 to 1/10).

97: ¹H NMR (400 MHz, CDCl₃) δ 7.98 (d, J = 1.2 Hz, 2H, Ar-H), 7,55 (t,1H, Ar-H), 7.41 (m, 3H, Ar-H), 7.35-7.29 (m, 7H, Ar-H), 7.15-7.09 (m, 6H, Ar-H), 5.30 (dd, J = 10.0, 8.4 Hz, 1H, H-2), 5.26 (t, J = 3.4 Hz, 1H, H-12), 5.10-5.02 (m, 2H, CO2CH2Ph), 4.80-4.58 (m, 5H, H-1′, H-5′, H-4′, OCH2Ph), 3.96-3.81 (m, 2H, OCH2Ph), 3.81 (m, 1H, H-3′), 3.74 (s, 3H, OCH3), 3.07-3.00 (m, 1H, H-3), 2.90-2.85 (m, 1H, H-18), 2.00-1.93 (m, 1H), 1.83-1.74 (m, 2H), 1.70-1.62 (m, 3H), 1.54-1.48 (m, 2H), 1.47-1.20 (m, 8H), 1.20-1.12 (m, 3H), 1.07 (s, 3H), 1.00-0.94 (m, 2H), 0.90 (s, 3H), 0.88 (s, 3H),0.84-0.82 (m, 1H), 0.80 (s, 3H), 0.65 (s, 3H), 0.60 (s, 1H, H-5), 0.56 (s, 3H), 0.53 (s, 3H) ppm;

BBD ¹³C NMR (100 MHz, CDCl3) δ 177.5, 168.9, 165.1, 143.8, 137.8, 137.7, 133.2, 130.0, 129.9, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.8, 122.7, 103.7 (C-1′), 90.5, 82.0, 79.5, 75.2, 75.1, 74.6, 73.7, 66.1, 55.6, 52.7, 47.7, 46.8, 46.0, 41.7, 41.5, 39.4, 38.9, 38.5, 36.7, 34.0, 33.2, 32.7, 32.5, 30.8, 29.8, 27.9, 27.7, 26.0, 25.8, 23.8, 23.5, 23.2, 18.2, 16.9, 16.3, 15.3 ppm; HRMS⁺ (ESI-TOF) calcd for C₆₅H₈₀O₁₀Na [M+Na]⁺ 1043.5644, found 1043.5638.

28-O-Allyl-3-O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranosyluronate)quillate (98) Compound 98 (15 mg, 17%) as a white solid: Rf 0.19 (EtOAc/Hexanes, 1/3) was synthesized according to method B by using 25 (50 mg, 0.104 mmol), 61 (46 mg, 0.0867 mmol) and B(PhF5)3 (5.3 mg, 0.0104 mmol) and purified by flash chromatography (silica gel, EtOAc/Hexanes, 1/4). 98: ¹H NMR (400 MHz, CDCl₃) δ 9.35 (s, 1H, H-23), 5.87-5.78 (m, 1H, OCH2CHCH2), 5.38 (t, J = 3.4 Hz, 1H, H-12), 5.29 (d, 1H, J = 17.08 Hz, OCH2CHCH2), 5.21-5.13 (m, 3H, H-3′, H-4′, OCH2CHCH2), 4.91 (dd, J = 8.2, 7.9 Hz, 1H, H-2′), 4.53-4.42 (m, 3H, H-16, OCH2CHCH2), 4.43 (d, J

= 7.9 Hz, 1H, H-1′), 3.97 (d, J = 9.4 Hz, 1H, H-5′), 3.78-3.73 (m, 4H, H-3, OCH3), 3.11-3.05 (m, 1H, H-18), 2.14 (t, J = 13.2 Hz, 1H, H-19), 2.07-2.04 (m, 4H), 2.00 (s, 3H), 1.99 (s, 3H), 1.81-1.68 (m, 4H), 1.79-1.65 (m, 6H), 1.50-1.38 (m, 2H), 1.34 (s, 3H), 1.30-1.20 (m, 3H), 1.17-1.05 (m, 3H), 1.00 (s, 3H), 0.96 (s, 3H), 0.94 (s, 3H), 0.91-0.89 (m, 4H), 0.70 (s, 3H) ppm; BBD ¹³C NMR (100 MHz, CDCl3) δ 206.4, 176.4, 170.2, 167.2, 132.3, 122.6, 118.3, 102.1 (C-1′), 83.4, 75.0, 72.5, 72.0, 71.0, 69.5, 65.3, 55.1, 53.1, 48.9, 48.8, 46.6, 46.5, 41.5, 40.7, 39.9, 38.2, 36.0, 32.9, 32.9, 30.9, 30.6, 27.1, 24.7, 20.7, 20.6, 17.1, 15.8, 10.1 ppm; HRMS⁺ (ESI-TOF) calcd for C46H67O14 [M+H]⁺ 843.4525, found 843.4525.

28-O-Allyl-3-O-(methyl 2,3,4-tri-O-benzoyl-β-D-glucopyranosyluronate)quillate (99)

Compound 99 (12 mg, 38%) as a white solid: R_f 0.23 (EtOAc/Hexanes, 1/4) was synthesized according to method B by using 31 (20 mg, 0.036 mmol), 61 (16 mg, 0.030 mmol) and B(PhF5)3 (1.5 mg, 0.0036 mmol) and purified by flash chromatography (silica gel, EtOAc/Hexanes, 1/5). 99: ¹H NMR (400 MHz, CDCl3) δ 9.19 (s, 1H, H-23), 7.95-7.81 (m, 6H, Ar-H), 7.54-7.26 (m, 9H, Ar-H), 5.86-5.82 (m, 2H, H-3′, OCH2CHCH2), 5.59 (dd, J = 9.6, 9.4 Hz, 1H, H-4′), 5.45 (dd, J = 9.7, 7.8 Hz, 1H, H-2′), 5.38 (t, J = 3.4 Hz, 1H, H-12), 5.28 (dd, J = 17.1, 1.4 Hz, 2H, OCH2CHCH2), 4.74 (d, J = 7.8 Hz, 1H, H-1′), 4.51-4.46 (m, 3H, H-16, OCH2CHCH2), 4.27 (d, J = 9.4 Hz, 1H, H-5′), 3.89-3.82 (m, 1H, H-3), 3.68 (s, 3H, OCH3), 3.05 (dd, J = 14.2, 3.5 Hz, 1H, H-18), 2.14 (t, J = 13.6 Hz, 1H, H-19), 2.02-1.83 (m, 4H), 1.81-1.68 (m, 5H), 1.50-1.38 (m, 4H), 1.31 (s, 3H), 1.30–1.20 (m, 3H), 1.17-1.05 (m, 3H), 1.01 (s, 3H), 0.96 (s, 3H), 0.92 (s, 3H), 0.89 (s, 3H), 0.85-0.82 (m, 1H), 0.68 (s, 3H) ppm; BBD ¹³C NMR (100 MHz, CDCl3) δ 208.3, 176.4, 167.4, 165.7, 165.4, 164.9, 142.9, 133.6, 133.4, 132.3, 130.0, 129.9, 129.2, 128.9, 128.8, 128.6, 128.5, 122.7, 118.3, 102.1 (C-1′), 83.4, 75.1, 72.8, 72.2, 71.5, 70.4, 65.3, 54.4, 53.0, 49.8, 48.8, 46.6, 46.5, 41.5, 40.7, 39.9, 38.2, 36.2, 35.5, 32.9, 32.3, 30.9, 30.5, 27.1, 25.0, 24.8, 23.4, 20.2, 17.1, 15.8, 10.7 ppm;

HRMS⁺ (ESI-TOF) calcd for C₆₁H₇₃O₁₄ [M+H]⁺ 1029.4995, found 1029.4995.

28-O-Allyl-3-O-(methyl

2,3,4-tri-O-tert-butyldimethylsilyl-β-D-glucopyranosiduronate) quillate (100)

Compound 100 (22.5 mg, 59%) as a colorless syrup: R_f 0.51 (EtOAc/Hexanes, 1/4) was synthesized according to method B by using compound 79 (30 mg, 0.043 mmol), 61 (19 mg, 0.036 mmol), B(PhF₅)₃ (2 mg, 0.0043 mmol) and was purified by column chromatography (silica gel, EtOAc/Hexanes, 1/15 to 1/8). 100: ¹H NMR (400 MHz, CDCl3) δ 9.39 (s, 1H, H-23), 5.90-5.82 (m, 1H, OCH2CHCH2), 5.38 (t, J = 3.4 Hz, 1H, H-12), 5.38-5.18 (m, 2H, OCH2CHCH2), 4.63 (d, J = 5.0 Hz, 1H, H-1′), 4.52-4.47 (m, 3H, OCH2CHCH2, H-16), 4.21 (d, 2H), 3.97-3.93 (m, 1H, H-3), 3.73 (s, 3H, OCH3), 3.66 (s, 1H), 3.56 (d, 1H), 3.09-3.02 (m, 1H, H-18), 2.14 (t, J = 13.6 Hz, 1H, H-19), 1.99-1.86 (m, 4H), 1.84-1.70 (m, 5H), 1.67-1.65 (m, 2H), 1.54-1.52 (m, 1H), 1.45-1.40 (m, 2H), 1.33 (s, 3H), 1.25-1.20 (m, 2H), 1.14-1.12 (m, 2H), 1.08 (s, 3H), 1.05-1.00 (m, 2H), 0.96 (s, 3H), 0.95 (s, 3H), 0.90 (s, 12H), 0.86 (s, 9H), 0.85 (m, 9H), 0.71 (s, 3H), 0.09 (s, 3H), 0.08 (s, 3H), 0.07 (s, 3H), 0.05 (s, 3H), 0.04 (s, 3H), 0.02 (s, 3H) ppm;

BBD ¹³C NMR (100 MHz, CDCl3) δ 206.9 (CHO), 176.5, 170.5, 142.9, 132.3 (OCH2CHCH2), 122.8 (C-12), 118.2 (OCH2CHCH2), 100.0 (C-1′), 78.8, 78.5, 75.1, 72.9, 65.3 (allylic CH₂), 54.9, 52.2, 48.9, 48.0, 46.8, 46.5, 41.5, 40.8, 39.9, 38.3, 36.0, 35.6, 35.6, 32.9, 32.4, 30.9, 30.5, 27.1, 26.0, 25.9, 24.8, 24.6, 23.4, 20.2, 18.0, 17.2, 15.7, 10.3, -4.1, -4.2, -4.3, -4.3 ppm; HRMS⁺ (ESI-TOF) calcd for C₅₈H₁₀₃O₁₁Si₃ [M+H]⁺ 1059.6803, found 1059.6815.

28-O-Allyl-3-O-(methyl

2-O-benzoyl-3,4-O-benzyl-β-D-glucopyranosyluronate)quillate (101)

Compound 101 (7.5 mg, 42%) as a white solid: R_f 0.31 (EtOAc/Hexanes, 1/3) was synthesized according to method B by using compound 90 (14 mg, 0.022 mmol), 61 (9.5 mg, 0.018 mmol) and B(PhF5)3 (1.0 mg, 0.0022 mmol). The purification of compound 101 was under flash column chromatography (silica gel, EtOAc/Hexanes, 1/10 to 1/6). 101: ¹H NMR (400 MHz, CDCl₃) δ 9.14 (s, 1H, H-23), 8.00 (d, J = 1.2 Hz, 2H, Ar-H), 7.59-7.28 (m, 6H, Ar-H), 7.25-7.09 (m, 7H, Ar-H), 5.87-5.78 (m, 1H, OCH2CHCH2), 5.36 (t, J = 3.4 Hz, 1H, H-12), 5.29-5.16 (m, 3H, OCH2CHCH2, H-2′), 4.78-4.58 (m, 4H, OCH2Ph, H-1′, H-5′), 4.50-4.42 (m, 4H, H-4′, H-16, OCH2CHCH2), 3.92 (dd, 2H, OCH2Ph), 3.75-3.70 (m, 5H, H-3′, H-3, OCH3), 3.08-3.01 (m, 1H, H-18), 2.14 (t, J = 13.6 Hz, 1H, H-19), 1.86-1.83 (m, 4H), 1.76-1.74 (m, 4H), 1.52-1.47 (m, 2H), 1.42-1.35 (m, 2H), 1.30 (s, 3H), 1.25 (s, 3H), 1.19-1.08 (m, 4H), 0.96 (s, 3H), 0.95 (s, 3H), 0.89 (s, 3H), 0.88 (s, 3H), 0.85-0.84 (m, 1H), 0.66 (s, 3H) ppm;BBD ¹³C NMR (100 MHz, CDCl3) δ 208.6, 176.5, 168.8, 165.1, 142.8, 137.7, 137.6, 133.3, 132.3, 129.9, 129.8, 128.6, 128.5, 128.4, 128.2, 128.1, 127.9, 122.7, 118.2, 102.5 (C-1), 83.2, 81.8, 79.4, 75.2, 75.0, 74.5, 73.3, 65.3, 54.5, 52.7, 49.7, 48.9, 46.6, 46.5, 41.5, 40.7, 39.9, 38.1, 36.2, 35.6, 32.9, 32.2, 30.8, 30.5, 29.8, 27.1, 25.0, 24.8, 23.4, 20.2, 17.1, 15.7, 10.7 ppm; HRMS⁺ (ESI-TOF) calcd for C₆₁H₇₆O₁₂Na [M+Na]⁺ 1023.5229, found 1023.5224.