JPH07109286A - Neohesperidose derivative - Google Patents

Abstract

PURPOSE:To obtain a novel derivative which is useful as an antiinflammatory agent of low toxicity because it has the inhibitory action against type III allergy. CONSTITUTION:A derivative of the formula I (R is monosaccharide, OHprotecting group, alkyl, alkenyl, alkinyl, sphingosine, cholesterol or their derivative), for example, the derivative of the formula II. For the synthesis of the derivative, after neohesperidose of the formula: Rhaalpha1 2Glc is synthesized, it is mixed with pyridine, acetic anhydride and a catalytic amount of 4-dimethylaminopyridine with stirring to effect the reaction, then treated with hydrazine acetate in DMF, allowed to react with trichloroacetonitrile in the presence of DBV to obtain a novel synthetic intermediate of the formula III. Further, the intermediate is allowed to react with, for example, octanol followed by deprotection of the product, or the reaction with N3-sphingosine followed by deprotection to introduce aglycon such as octyl or sphingosine into the glucose residue.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to glucose derivatives, particularly oligosaccharides and oligosaccharide derivatives having an anti-inflammatory effect.

[0002]

2. Description of the Related Art An anti-inflammatory agent acts to suppress inflammation, which is originally a biological defense reaction, when it becomes excessive and harmful to the living body. In addition, anti-inflammatory agents are roughly classified into steroid-based and non-steroidal ones, and as typical steroid-based anti-inflammatory agents, hydrocortisone, prednisolone and the like are known.

[0003]

However, not to mention steroidal anti-inflammatory agents, even non-steroidal anti-inflammatory agents are toxic as represented by aspirin and the heterocyclic compound indomethacin. Many problems remain in terms of aspects.

The present invention has been made in view of the above problems, and an object thereof is to provide an anti-inflammatory agent having low toxicity.

[0005]

In order to solve the above problems, the present invention is characterized in that the anti-inflammatory agent is composed of oligosaccharides and oligosaccharide derivatives.

[0006] This was found to have a strong anti-inflammatory effect when the synthesis and biological activity screening of neohesperidose (Rhaα1 → 2Glc), which is a disaccharide contained in naringin which is one of flavonoid glycosides, was carried out. It is based on the fact that it turned out.

Therefore, the present invention includes an anti-inflammatory agent containing neohesperidose (Rhaα1 → 2Glc).

The inventors of the present application conducted the synthesis of a series of compounds by examining the number of rhamnose in neohesperidose, position isomers, conversion of rhamnose, introduction of aglycone, and the like, and examined the structure-activity relationship. And provided a new type of anti-inflammatory agent containing a sugar chain.

This series of compounds is represented by the following general formula.

[0010]

[Chemical 3] Here, the number of rhamnose in neohesperidose can be selected as an arbitrary number of 1 or more.

The conversion of rhamnose can be carried out, for example, by converting rhamnose into fucose, glucose, galactose xylose, sialic acid or arabinose.

The aglycones introduced into glucose are, for example, hydrocarbons such as octyl, propyl and allyl, halogens such as fluorine, sphingosine, ceramide, cholesterol, ursolic acid and derivatives thereof.

As the binding site for sugar or aglycone, any of the 1- to 6-positions of glucose can be used.

The introduction of aglycone into the glucose residue can be carried out via a synthetic intermediate represented by the following formula.

[0015]

[Chemical 4]

[0016]

ACTION AND EFFECTS The compounds of the present invention as described above are oligosaccharides and their derivatives whose anti-inflammatory action has not been recognized in the past. Has an inflammatory effect.

Therefore, these compounds can be used as novel anti-inflammatory agents, for example, therapeutic agents for renal diseases which suppress nephritis.

[0018]

【Example】

(I) Synthesis of compound Unless otherwise specified, the starting materials are Tokyo Kasei Co., Ltd.
I am using the reagent.

[0019]

Example 1 Synthesis of neohesperidose 5 (FIG. 1) 1 + 2 → 3 1 , 582.7 mg (1.0 mmol), 2 , 480.5 mg
(1.5 mmol), molecular sieve 4A (1.0 g) and 1,2-dichloroethane (5 ml) were stirred while stirring at -15 ° C. 574.5 mg (3.0 mmol) of nyl chloride was added,
Stir for 30 minutes. After diluting with ethyl acetate, the mixture was filtered through Celite, and the filtrate was washed with saturated aqueous sodium hydrogen carbonate and saturated brine. After drying the organic layer with magnesium sulfate, the solvent was distilled off. The residue was purified by SX-8 column (toluene) and silica gel column (toluene: ethyl acetate = 4: 1) to give 3 to 7.
Obtained 59.4 mg (86.6%).

[Physical Properties of Compound 3 ] Rf = 0.28 (toluene: ethyl acetate = 5: 1) δ _H (CDCl ₃ , TMS) 5.270 (dd, 1H, J = 1.46Hz, 3.66Hz, H-2b ) 5.207 (dd, 1H, J = 3.66Hz, 10.26Hz, H-3b) 5.137 (dd, 1H, J = 1.46Hz, H-1b) 4.482 (dd, 1H, J = 7.33Hz, H-1a) 3.681 (T, 1H, J = 8.42Hz, H-3a) 3.642 (t, 1H, J = 8.79Hz, H-4a) 1.987, 1.984, 1.955 (3s, 9H, 3Ac) 0.825 (d, 1H, J = 6.23 Hz, H-6b)

[Chemical 5] 3 , 512.7 mg (0.63 mmol), MeOH 15 ml,
0.2 ml of NaOMe (5.2N) was stirred at room temperature for 1 hour, treated with Amberlyst 15E, and the solvent was distilled off to obtain 429.5 mg (99.2%) of 4 .

[Physical Properties of Compound 4 ] Rf = 0.49 (chloroform: MeOH = 10: 1) δ _H (CDCl ₃ , TMS) 5.109 (br-s, 1H, H-1b) 4.402 ( d, 1H, J = 7.69Hz, H-1a) 0.988 (d, 1H, J = 6.22Hz, H-6b) 4 → 5 4 of 541.2mg of (0.79mmol) MeOH: H ₂ O
= (4: 1) suspended in 125 ml, replaced with Ar gas,
It was stirred. Next, 541.2 mg of Pd (OH) ₂ -C was added, the atmosphere was replaced with H ₂ gas, and the mixture was stirred day and night. After filtration through Celite, the solvent was removed by filtration. The residue was purified by LH-20 (chloroform: MeOH = 1: 1) column, and 197.4 mg (76.) of neohesperidose 5 was added.
8%) (α / β = 3/1).

[Physical Properties of Compound 5 ] Rf = 0.33 (ethyl acetate: EtOH: H ₂ O = 5:
2: 1) Elemental analysis C ₁₂ H ₂₂ O ₁₀ theoretical value C; 44.17 H; 6.80 measured value C; 43.73 H; 6.86 δ _H (CD ₃ OD, TMS) 5.221 (α , 0.75H, J = 3.67Hz, H-1a
α) 5.161 (d, 0.25H, J = 1.47Hz, H-1b
β) 4.909 (d, 0.75H, J = 1.47Hz, H-1b
α) 4.529 (d, 0.25H, J = 7.7Hz, H-1aβ) 3.981 (dd, 0.75H, J = 1.47Hz, 3.3Hz, H-2b
α) 1.252 (d, 3H, J = 6.23Hz, H-6b)

[0023]

[Example 2] Synthesis of intermediate for synthesis of neohesperidose derivative (Fig. 1) A mixture of 5 → 6 neohesperidose 5 (290 mg, 0.89 mmol), pyridine 25 ml, acetic anhydride 25 ml, and catalytic amount of 4-dimethylaminopyridine. Was stirred at room temperature for 3 days. The solvent was distilled off, and the residue was purified by silica gel column (toluene: ethyl acetate = 1: 1) to obtain 464 mg (84%) of 6 .

[Physical Properties of Compound 6 ] Rf = 0.48 (toluene: acetone = 3: 1) δ _H (CDCl ₃ , TMS) 6.309 (d, 0.75H, J = 3.7 Hz, H- 1a
α) 5.679 (d, 0.25H, J = 8.4Hz, H-1a
β) 5.288 (t, 0.75H, J = 9.5Hz, H-3a
α) 4.906 (br-s, 0.25H, H-1bβ) 4.889 (br-s, 0.75H, H-1bα) 6 → 7 6 (196 mg, 0.32 mmol), hydrazine acetic acid ( Four
4 mg, 0.48 mmol) and 2 ml of DMF at room temperature.
Stir for hours. After diluting with ethyl acetate, the mixture was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, the organic layer was dried over magnesium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (toluene: acetone = 3: 1) 7 159 mg (87
%)Obtained.

[Physical Properties of Compound 7 ] A solution of Rf = 0.44 (toluene: acetone = 3: 1) 7 → 8 7 (152 mg, 0.26 mmol) in 1,2-dichloroethane (2 ml) was stirred under ice-cooling and trichloromethane was added. Acetonitrile (264 μl, 2.6 mmol), DBU (79 μl, 0.
(52 mmol) was added sequentially and the mixture was stirred for 4 hours. The reaction solution was purified by silica gel column (toluene: acetone = 5: 1).
˜3: 1), and imidate body 8 (165 mg, 87%), which is a synthetic intermediate zone of the neohesperidose derivative, was obtained.

[Physical Properties of Compound 8 ] Rf = 0.50 (toluene: acetone = 4: 1) [α] ²² _D + 37.3 ° (C = 1.2, chloroform) δ _H (CDCl ₃ , TMS) 8.778 (s, 1H, NH ) 6.463 (d, 1H, J = 3.7Hz, H-1a) 5.522 (t, 1H, J = 9.9Hz, H-3a) 5.195 (Dd, 1H, J = 3.3, 10.2Hz, H-
3b) 5.117 (t, 1H, J = 9.9Hz, H-4a) 4.911 (s, 1H, H-1b) 4.296 (dd, 1H, J = 4.0, 12.4Hz, H-
6a) 3.990 (dd, 1H, J = 3.7, 9.9 Hz, H-6)
a ') 2.133, 2.106, 2.066, 2.043, 2.006, 1.963 (6s, 18H, 6xAc) 1.169 (d, 3H, J = 6.2Hz, H -6b)

[0027]

Example 3 Synthesis of Neohesperidose Derivative from Intermediate (Imidate Form 8 ) Synthesis of Rhaα1-2Glc-Oct (FIG. 2) Synthesis of Neohesperidose Octyl Derivative (Protected Form) 8 → 10 + 13 Activated Molecular sieve 4A, 300mg, 1,
Imidate compound 8 , 8 dissolved in 2 ml of 2-dichloroethane
5 mg (0.118 mmol) and octanol 37 μl
(0.235 mmol) was added and the mixture was kept at room temperature for 20 minutes at -10 ° C.
After stirring for 40 minutes at -10 ° C, BF ₃ · Et ₂ O,
29 μml (0.235 mmol) was added. 50 at -10 ° C
The mixture was stirred for 3 minutes at 0 ° C. for 3 hours, triethylamine was added for neutralization, the mixture was diluted with chloroform, and filtered through Celite. The filtrate was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was separated and purified by silica gel chromatography (toluene: acetone = 10: 1) to obtain 32.8 mg of a mixture of 10 and 13 .

Subsequently, the mixture was TLC (toluene:
Separated and purified with acetone = 10: 1), oily product 10 1
5.0 mg (Yield: 18.5%) and 13 to give 28.5 mg. Α of compound 10 by 500 MHz ¹ H-NMR
The mixture ratio of the isomer-β isomer was 1: 7, and the mixture ratio of the α-β isomer of compound 13 was 1: 1.

[0029] [Physical properties of Compound 10] molecular formula C ₃₂ H ₅₀ O ₁₆ Molecular weight 690.736 FAB (+) MS 691 ( M + H) + 1 H-NMR neohesperidose-octyl derivative (protector) 10 Rf = 0. 19 (toluene: acetone = 10: 1) δ _H (CDCl ₃ , TMS) 5.061 (t, 1H, J = 10.2 Hz, H-4b) 4.456 (d, 1H, J = 7.7 Hz, H-1aβ) 4.108 (dd, 1H, J = 12.1, 2.5Hz, H
-6a) 1.197 (d, 0.39H, J = 6.2Hz, H-6b
α) 1.173 (d, 2.61H, J = 6.2Hz, H-6b
β) 2.128, 2.078, 2.065, 2.038, 2.011, 1.994 (6s, 18H, 6
× Ac) Synthesis of neohesperidose octyl derivative (deprotected form) 10 → 11 10 15 mg (22 μmol) was dissolved in 2 ml of methanol, and 5.9 mg (43 μmol) of potassium carbonate was added at room temperature and stirred for 2 hours. The reaction solution is a gel filtration column LH-2
The mixture was placed on 0 and eluted with methanol, and the solvent of the obtained fraction was distilled off under reduced pressure to give 8.1 mg ( 11 ; yield 85.1%) of an oily substance.
Got

[Physical Properties of Compound 11 ] Molecular Formula C ₂₀ H ₃₈ O ₁₀ Molecular Weight 438.514 FAB (−) MS 437 (M−H) ⁺ Neohesperidose Octyl Derivative (Deprotected Form) 1
1 Rf = 0.70 ( ^n- butanol: ethanol: water = 2:
1: 1) δ _H (CD ₃ OD, TMS) 4.307 (d, 1H, J = 7.7 Hz, H-1aβ) 1.249 (d, J = 6.2 Hz, H-6bα) 1.218 (D, J = 6.1 Hz, H-6bβ) IR ν KBr, cm ⁻¹ 3.416 (O−H), 1.062 (C−O) Synthesis of Rhaα1 → 2Glc → F (FIG. 2) 13 → 14 13 (19 mg, 33 μmol), methanol 0.5 ml, 1
A mixture of 60 μl N sodium methoxide was stirred overnight at room temperature. The reaction solution was purified by LH-20 (methanol) to obtain 7.5 mg (70%) of 14 . (Β: α = 2:
1) [Physical Properties of Compound 14 ] Rf = 0.53,0.42 ( ^n- butanol: ethanol: water = 2: 1: 1) δ _H (CD ₃ OD, TMS) 5.670 (dd, 0.33H, J = 2.6, 53.8Hz, H-1aα) 5.147 (dd, 0.67H, J = 7.0, 53.8Hz, H-1aβ) 5.133 (br-s, 0.67H, H-1bβ) 4.920 ( br-s, 0.33H, H-1bα) 1.250 (d, 2H, J = 6.2Hz, H-6bβ) 1.228 (d, 2H, J = 6.2Hz, H-6bα) Rhaα1 → 2Glc Synthesis of azidosphingosine (Fig. 3) Rhaα1 → 2Glc Synthesis of protected azidosphingosine 8 + 16 → 17α + 17β Activated molecular sieve 4A 1,2 per 300 mg.
-Imidate compound 8 , 7 dissolved in 2 ml of dichloroethane
8.5 mg (0.109 mmol) and N ₃ - sphingosine
16 , 70 mg (0.163 mmol) was added, and the mixture was stirred at room temperature for 20 minutes and at -10 ° C for 40 minutes, and then at -10 ° C for BF _3.
-Et ₂ O 27 μl (0.217 mmol) was added. −
The mixture was stirred at 10 ° C for 50 minutes and at 0 ° C for 2.5 hours, neutralized by adding triethylamine, and then diluted with chloroform.
Celite filtration was performed. The filtrate was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure.

The resulting residue was separated and purified by silica gel column chromatography (toluene: acetone = 10: 1) to obtain 96.2 mg of a mixture of 16 , 17α and 17β and a mixture of α: β = 7: 1 in 33. 6 mg (yield 53.1
%)Obtained. For TLC The 16, a mixture of 17α and 17ß (toluene: acetone = 4: 1) at separation and purification, 16, the mixture 30 of 50.6 mg (recovery rate 72.3%) and 17α及<br/> beauty 17ß 4 mg was obtained. 17α and 17
The mixture of β was separated by HPLC (* 1) to obtain 9.5 mg of α-form ( 17α : yield 8.8%) and 17.2 mg of β-form ( 17β : yield 15.9%) as an oily substance. Obtained.

* 1 HPLC separation conditions Developing solvent A Water: trifluoroacetic acid = 100: 0.1 Developing solvent B Acetonitrile: water: trifluoroacetic acid =
95: 5: 0.1 0 to 1 min → 30 min → 60 min A: B = 50: 50 → 0: 100 → 0: 100 Flow rate 23 ml / min [Physical properties of compound 17α ] Molecular formula C ₄₉ H ₇₁ N ₃ O ₁₈ Molecular weight 990. 11 Neohesperidose / azidosphingosine derivative α
(Protected body) 17α Rf = 0.43 (toluene: acetone = 4: 1) δ _H (CDCl ₃ , TMS) 8.069-8.050 (m, 2H, H-2Bz, 6B)
z) 7.608-7.573 (m, 1H, H-4Bz) 7.479-7.448 (m, 2H, H-3Bz, 5B)
z) 5.443 (t, 1H, J = 9.9Hz, H-3a) 5.282 (dd, 1H, J = 9.9, 3.7Hz, H-
3b) 5.109 (dd, 1H, J = 3.7, 1.8Hz, H-
2b) 4.968 (d, 1H, J = 3.7 Hz, H-1a) 4.832 (d, 1H, J = 1.8 Hz, H-1b) 4.262 (dd, 1H, J = 12. 1,4.4Hz, H
-6a) 4.053 (dd, 1H, J = 12.1, 2.2Hz, H
-6a ') 3.982 (ddd, 1H, J = 9.9, 4.4, 2.2Hz, H-
5a) 2.138, 2.088, 2.038, 2.022,
1.970 (5s, 18H, 6xAc) 1.196 (d, 3H, J = 6.2Hz, H-6b) 0.878 (t, 3H, J = 7.0, H-18sphin) [Compound Physical Properties of 17β ] Molecular Formula C ₄₉ H ₇₁ N ₃ O ₁₈ Molecular Weight 990.11 Neohesperidose Azidosphingosine Derivative β
(Protected body) 17β Rf = 0.43 (toluene: acetone = 4: 1) δ _H (CDCl ₃ , TMS) 8.056-8.036 (m, 2H, H-2Bz, 6B)
z) 7.597-7.561 (m, 1H, H-4Bz) 7.468-7.438 (m, 2H, H-3Bz, 5B)
z) 5.246 (dd, 1H, J = 9.9, 3.3 Hz, H-
3b) 5.221 (t, 1H, J = 9.5 Hz, H-3a) 5.066 (t, 1H, J = 9.9 Hz, H-4b) 5.023 (dd, 1H, J = 3. 3, 1.8Hz, H-
2b) 4.976 (t, 1H, J = 9.9Hz, H-4a) 4.970 (d, 1H, J = 1.8Hz, H-1b) 4.478 (d, 1H, J = 7. 7Hz, H-1a) 4.163 (dd, 1H, J = 12.1, 5.1Hz, H
-6a) 4.076 (dd, 1H, J = 12.1, 2.6Hz, H
-6a ') 3.740 (dd, 1H, J = 9.5, 7.7Hz, H-
2a) 3.672 (ddd, 1H, J = 9.9, 5.1, 2.6)
Hz, H-5a) 2.131, 2.077, 2.009, 2.005,
1.989 (6s, 18H, 6xAc) 0.878 (t, 3H, J = 7.0Hz, H-18sphin
) Deprotection of Rhaα1 → 2Glc azidosphingosine protected form (α) 17α → 18α 17α , 8.8 mg (8.89 μmol) of methanol was added to 0.8%.
It was dissolved in 5 ml, 1N NaOH (0.1 ml) was added at 0 ° C., and the mixture was stirred at room temperature for 3.5 hr. The reaction solution was placed on a gel filtration column LH-20 and eluted with methanol, and the solvent in the obtained fraction was distilled off under reduced pressure to give 5.1 mg ( 18) of a white powder.
α : yield 90.5%) was obtained.

[Physical Properties of Compound 18α ] Molecular Formula C ₃₀ H ₅₅ N ₃ O ₁₁ Molecular Weight 633.78 Melting Point 149-152 ° C. IR ν KBr cm ^-1 3420 (O-H), 2924, 2854 (C-H),
1054 (CO) FAB (-) MS 632 (MH) ⁺ neohesperidose azidosphingosine derivative α
(Protected body) 18α Rf = 0.65 ( ^n- butanol: acetic acid: water = 7: 2:
5) δ _H (CD ₃ OD, CD ₃ OH) 4.931 (d, 1H, J = 3.7 Hz, H-1a) 4.921 (d, 1H, J = 1.8 Hz, H-1b) 4 0.030 (dd, 1H, J = 3.3, 1.8 Hz, H-
2b) 3.776 (dd, 1H, J = 9.5, 3.7 Hz, H-
3b) 3.729 (dd, 1H, J = 11.7, 5.5Hz, H
-6a) 3.631 (ddd, 1H, J = 9.9, 5.5, 2.2Hz, H-
5a) 1.304 (d, 3H, J = 6.2Hz, H-6b) 0.941 (t, 3H, J = 7.0Hz, H-18sphin
) Deprotection of Rhaα1 → 2Glc azidosphingosine protected form (β) 17β → 18β 17β 15.3 mg (15.5 μmol) of methanol 2
It was dissolved in 0.1 ml of 1N NaOH at 0 ° C., and the mixture was stirred at room temperature for 1 hr. The reaction solution is gel filtration column L
The mixture was placed on H-20 and eluted with methanol, and the solvent of the obtained fraction was evaporated under reduced pressure to give a white powder of 9.4 mg ( 18β : yield 9
5.7%) was obtained.

[Physical Properties of Compound 18β ] Molecular Formula C ₃₀ H ₅₅ N ₃ O ₁₁ Molecular Weight 633.78 Melting Point 141-143 ° C. IR ν KBr cm ^-1 3404 (O-H), 2924, 2854 (C-H),
1047 (CO) FAB (-) MS 632 (MH) ⁺ neohesperidose azidosphingosine derivative β
(Deprotected form) 18β Rf = 0.59 ( ^n- butanol: acetic acid: water = 7: 2:
5) δ _H (CD ₃ OD, CD ₃ OH) 5.271 (d, 1H, J = 1.8 Hz, H-1b) 4.388 (d, 1H, J = 7.7 Hz, H-1a) 3 .953 (dd, 1H, J = 3.3, 1.8 Hz, H-
2b) 1.306 (d, 3H, J = 6.2Hz, H-6b) 0.942 (t, 3H, J = 7.0Hz, H-18sphin
) Synthesis of cholesterol derivative of neohesperidose (Fig. 4)

[Chemical 6] Activated molecular sieve 4A, 750 mg, 1,
Imidate compound 8 , 1 dissolved in 2 ml of 2-dichloroethane
02.3mg (0.14mmol) and 1,2-dichloroethane cholesterol 20 was dissolved in 3ml, 151.0mg
(0.39 mmol) was added, and the mixture was added at room temperature for 40 minutes and at -7 ° C for 5 minutes.
After stirring for 0 minutes, BF ₃ · Et ₂ O, 50 μ at −7 ° C.
1 (0.41 mmol) was added. After stirring at -7 ° C for 3 hours,
Triethylamine 2 was diluted by adding 5 ml of chloroform.
After neutralizing by adding 0 μl, filtration was performed with a 0.45 μm filter. The filtrate was diluted with chloroform to a total volume of about 120 ml and saturated aqueous sodium hydrogen carbonate solution 70 m
34 ml of a pale yellow residue obtained by washing with 1, then 50 ml of saturated saline and drying over anhydrous magnesium sulfate, and distilling off the solvent under reduced pressure, was subjected to silica gel column chromatography (toluene: acetone = 20: 1-10: 1 to 4: 1)
3. Separation and purification were carried out with 21β , 21α , 13β , 13α as white powders, respectively, 42.6 mg (32.1%), 4.
4 mg (3.3%), 21.6 mg (26.6%), 35.
2 mg (43.3%) were obtained.

Induction of neohesperidose cholesterol
Body β (protected form) 21β Rf = 0.23 (toluene: acetone = 10: 1) δ _H (CDCl ₃ , TMS) 5.392 (m, 1H, cholesterol H-6) 5.266-5.225 ( m, 2H, H-3a, H-3
b) 5.068 (dd, 1H, J = 10.3, 9.9Hz, H
-4b) 5.002 (m, 1H, H-2b) 4.963 (d, 1H, J = 2.2Hz, H-1b) 4.960 (m, 1H, H-4a) 4.586 (d , 1H, J = 7.7 Hz, H-1a) 4.396 (dq, 1H, J = 6.2 Hz, H-5b) 4.273 (d, 1H, J = 12.5, 5.1 Hz, H −
6a) 4.077 (dd, 1H, J = 2.6Hz, H-6a ') 3.717 (dd, 1H, J = 9.5Hz, H-2a) 3.687 (ddd, 1H, J = 4) .8 Hz, H-5a) 3.617 (m, 1H, cholesterol H-3) 2.126, 2.070, 2.058, 2.019,
2.007, 1.991 (6s, 18H, 6 × Ac) 1.196 (d, 3H, J = 6.2Hz, H-6b) [Physical properties of compound 21β ] C ₅₁ H ₇₈ O ₁₆ = 947. 17 FAB (−) MS 945 (MH) ⁺ [Physical properties of compound 21α ] C ₅₁ H ₇₈ O ₁₆ = 947.17 neohesperidose cholesterol derivative α (protected
Body) 21α Rf = 0.23 (toluene: acetone _{= 10: 1) δ H (} CDCl 3, TMS) 5.447-5.225 (dd, 1H, J = 9.9, 9.5H
z, H-3a) 5.365 (m, 1H, cholesterol H-6) 5.247 (dd, 1H, J = 10.3, 3.3Hz, H
-3b) 5.080 (dd, 1H, J = 3.3, 1.8Hz, H-
2b) 5.053 (d, 1H, J = 4.0 Hz, H-1a) 5.046 (dd, 1H, J = 9.5 Hz, H-4b) 4.970 (dd, 1H, J = 10. 3Hz, H-4a) 4.842 (d, 1H, H-1b) 4.260 (dd, 1H, J = 12.1, 5.1Hz, H
-6a) 4.123 (ddd, 1H, J = 1.8Hz, H-5a) 4.076 (dd, 1H, H-6a ') 3.921 (dq, 1H, J = 6.2Hz, H- 5b) 3.699 (dd, 1H, H-2a) 3.444 (m, 1H, cholesterol H-3) 2.135, 2.085, 2.077, 2.041,
2.033, 1.990 (6s, 18H, 6 × Ac) 1.191 (d, 3H, H-6b) ¹ H-NMR [Physical properties of compound 13β ] C ₂₄ H ₃₃ O ₁₅ = 580.52 Rf = 0.32 (toluene: acetone = 4: 1) ¹ H-NMR (500 MHz, δ, ppm) 5.313 (1H, d, J _{1a, F} = 45.
4, J _{1a, 2a} = 6.6Hz; 1a) [Physical properties of compound 13α ] C ₂₄ H ₃₃ O ₁₅ = 580.52 Rf = 0.32 (toluene: acetone = 4: 1) ¹ H-NMR (500MHz, δ, ppm) 5.705 (1H, dd, J _{1a, F} = 52.
4, J _{1a, 2a} = 2.6Hz ; 1a) 21β , 14.0 mg (15 μmol) in methanol 2.5
Dissolve in 4 ml of potassium carbonate at room temperature 4.1 mg (30 μmo
l) was added and stirred for 1.3 hours. The reaction solution was placed on a gel filtration column LH-20 and eluted with methanol, and the solvent of the obtained fraction was distilled off under reduced pressure to obtain white powder 22β , 11 mg (quantitative).

[Physical Properties of Compound 22β ] C ₃₉ H ₆₀ O ₁₀ = 694.95 mp 235 to 237 ° C. (uncorrected) IR ν KBr cm ⁻¹ 3400 (OH, str), 2932 (CH, str), 1
051 (CO, str) FAB (+) MS 695 (M + H) ⁺ 717 (M + Na) ⁺ neohesperidose cholesterol derivative (deprotection
22β Rf = 0.58 ( ^n- butanol: ethanol: water = 2:
1: 1) δ _H (CD ₃ OD, TMS) 5.376 (m, 1H, cholesterol H-6) 5.190 (d, 1H, H-1b) 4.474 (d, 1H, J = 7. 7Hz, H-1a) 4.134 (dq, 1H, J = 9.5, 6.2Hz, H-
5b) 3.841 (dd, 1H, J = 9.5, 1.8 Hz, H-
6a) 3.659 (dd, 1H, J = 3.3 Hz, H-6a ') 1.235 (d, 3H, H-6b) 21α , 5.0 mg (5.3 μmol) in methanol 1.5.
2.0 ml of potassium carbonate at room temperature (14.5
μmol) was added and the mixture was stirred for 2 hours. The reaction solution was placed on a gel filtration column LH-20 and eluted with methanol, and the solvent of the obtained fraction was distilled off under reduced pressure to obtain 22 mg of white powder, 4.1 mg.
(Quantitative) was obtained.

[Physical Properties of Compound 22α ] C ₃₉ H ₆₆ O ₁₀ = 694.95 m.p. p. 240-244 ° C (uncorrected) FAB (+) MS 717 (M + Na) ^{+ 1} H-NMR neohesperidose cholesterol derivative (deprotection)
22α Rf = 0.55 ( ^n- butanol: ethanol: water = 2:
1: 1) δ _H (CD ₃ OD, TMS) 5.365 (m, 1H, cholesterol H-6) 4.996 (d, 1H, J = 3.3 Hz, H-1a) 1.244 (d, 3H, J = 6.2 Hz, H-6b) Neoheperidose ceramide derivative (Rhaα1 →
Synthesis of 2Glc1 → Cer) (FIG. 5) Synthesis of Rhaα1 → 2Glc1 → Cer protected compound 8 + 25 → 26α + 26β imidate compound 8 (42 mg, 58 μmol), ceramide derivative (Bz-Cer) 25 (66 mg, 87 μmol), molecular Sieve 4A (600 mg), chloroform 1.5
After stirring the mixture of ml at room temperature for 20 minutes, the reaction solution was cooled to -12 ° C.
Cool down to boron trifluoroetherate (11μ
1, 120 μmol) was added and the mixture was further stirred for 1 hour. The reaction solution was neutralized with triethylamine, diluted with chloroform, filtered through Celite, and the filtrate was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over magnesium sulfate, the solvent was evaporated, and the residue was purified by silica gel column (toluene:
Acetone = 5: 1) and 14.5 mg (1
9%) and 3 mg (4%) of α-form 26α were obtained. Further, as a decomposition product of the imidate body 8, a fluorine-substituted compound 13 19
mg (56%) (β: α = 5: 2) was obtained.

[Physical properties of compound 26β ] Rf = 0.29 (toluene: acetone = 8: 1) δ _H (CDCl ₃ , TMS) 8.02 to 7.25 (m, 5H, Aromatic proton) 5.937 (d, 1H, J = 8.4Hz , -N H) 5.874 (dt, 1H, J = 7.7,15.4Hz, 5Ce
r) 5.642 (t, 1H, J = 7.4Hz, 3Cer) 5.499 (dd, 1H, J = 7.4, 15.4Hz, 4Ce)
r) 4.980 (s, 1H, H-1b) 4.464 (m, 1H, H-5b) 4.405 (d, 1H, J = 7.7Hz, H-1a) 2.132, 2. 089, 2.039, 2.002,
1.979.1, 963 (6S, 18H, 6xAc) 1.198 (d, 3H, J = 6.2Hz, H-6c) 0.878 (t, 6H, J = 7.0Hz, Mex) 2) 26α Rf = 0.40 (toluene: acetone = 8: 1) δ _H (CDCl ₃ , TMS) 8.02 to 7.23 (m, 5H, Aromatic proton) 6.162 (d, 1H, J = 9.5Hz, -NH) 5.940 (dt, 1H, J = 7.7, 15.0Hz, 5c
er) 5.611 (t, 1H, J = 7.7Hz, 3cer) 5.466 (t, 1H, J = 9.5Hz, H-3a) 5.312 (dd, 1H, J = 3.3) 10.3Hz, H-
3b) 4.942 (d, 1H, J = 2.9 Hz, H-1a) 4.902 (d, 1H, J = 1.1 Hz, H-1b) 4.524 (m, 1H, H-5b) 2.137, 2.083, 2.048, 2.020,
1.985, 1.968 (6S, 18H, 6 × Ac) 0.878 (t, 6H, J = 7.0 Hz, Me × 2) [Physical properties of compound 13 ] Rf = 0.68 (chloroform: methanol) = 40:
1) Rhaα1 → 2Glcβ1 → deprotection of Cer protection body 26β → 27β 26β (9mg, 6.8μmol ), tetrahydrofuran:
A mixture of 0.5 ml of methanol = 1: 1 and 0.15 ml of 1N NaOH was stirred at room temperature for 8 hours, and then the reaction solution was mixed with LH-20 (chloroform: methanol: water = 60: 3).
0: 5), and deprotected 27β was 6.5 mg (99
%)Obtained.

[Physical Properties of Compound 27β ] Rf = 0.83 ( ⁿ -butanol: ethanol: water =
2: 1: 1) δ _H (DMSOd ₆ : D ₂ O = 49: 1, TMS) 5.560 (dt, 1H, J = 7.3, 15.4 Hz, 5c)
er) 5.318 (dd, 1H, J = 7.0, 15.4Hz, 4c)
er) 5.173 (s, 1H, H-1b) 4.178 (d, 1H, J = 7.7Hz, H-1a) 1.106 (d, 3H, J = 6.2Hz, H-6b) 0.847 (t, 6H, J = 7.0 Hz, Me × 2) Rhaα1 → 2Glcα1 → Cer Deprotection of protected body 26α → 27α 26α (2.6 mg, 1.97 μmol), tetrahydrofuran: methanol = 1: 1 0.5 ml and 1N NaO
A mixture of 0.1 ml of H was stirred at room temperature for 2 hours. The reaction solution was purified with LH-20 (methanol) to give 27α of 1.
9 mg was obtained quantitatively. [Physical Properties of Compound 27α ] Rf = 0.85 (chloroform: methanol: water = 6
0: 30: 5) δ _H (DMSOd ₆ : D ₂ O = 49: 1, TMS) 5.599 (dt, 1H, J = 7.7, 15.4 Hz, 5c)
er) 5.359 (dd, 1H, J = 7.3, 15.4Hz, 4c
er) 4.715 (s, 1H, H-1b) 4.639 (d, 1H, J = 3.7Hz, H-1a) 1.117 (d, 3H, J = 6.2Hz, H-6b) 0.852 (t, 6H, J = 7.0 Hz, Me × 2) Rhaα1 → 2Glcβ1 → Synthesis of ursolic acid (FIG. 6) Rhaα1 → 2Glcβ1 → Synthesis of protected ursolic acid 8 + 30 → 31 Imidate 8 (52 mg) , 72 μmol), ursolic acid methyl ester 30 (126 mg, 268 μmol), molecular sieve 4A (500 mg) and 1.2 mg of 1.2-dichloroethane were stirred at room temperature for 20 minutes, then cooled to -12 ° C. and stirred for 10 minutes. Boron trifluoroetherate (13 μl, 142 μmol) was added and the mixture was stirred for 2.5 hours. The reaction solution was neutralized with triethylamine, diluted with chloroform, and filtered through Celite. The filtrate was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, the organic layer was dried over magnesium sulfate, and the solvent was evaporated. After the gel filtration was performed at residue SX-8 (toluene), preparative TLC (toluene: ethyl acetate = 5: 1) to give 31 18
mg (β / α = 2 / 1,24%) was obtained.

[Physical Properties of Compound 31 ] δ _H (CD ₃ OD, TMS) 5.113 (d, 0.33 H, J = 4.0 Hz, H-1a)
α) 5.007 (s, 0.67H, H-1bβ) 4.895 (d, 0.33H, J = 1.5Hz, H-1b
α) 4.540 (d, 0.67H, J = 7.7Hz, H-1a)
β) 3.606, 3.601 (2s, 3H, CO ₂ Me ) Deesterification reaction 31 → 32α + 32β 31 (11 mg, 11 μmol), lithium iodide (42 m
g, 314 μmol) and 1 ml of pyridine were refluxed for 17 hours. The reaction solution was passed through LH-20 (methanol), and then purified by silica gel column (toluene: ethyl acetate = 3: 2) to obtain 4.3 mg of a mixture of 32β (β-form) and 32α (α-form). Then, 5.7 mg of 31 (recovery rate 51.8%) was recovered.

A mixture of β-form and α-form was prepared by preparative TL.
2 mg of pure β-form 32β , (1
1 mg of α-form 32α was obtained (5.5%).

[Physical Properties of Compound 32β ] Rf = 0.44 (toluene: ethyl acetate = 2: 1) δ _H (CD ₃ OD, TMS) 5.285 (t, 1H, J = 9.5 Hz, H- 4b) 4.996 (t, 1H, J = 9.5 Hz, H-3a) 4.909 (t, 1H, J = 9.5 Hz, H-4a) 4.690 (d, 1H, J = 7. 7 Hz, H-1a) 2.115, 2.045, 2.015, 2.008,
1.985, 1.954 (6s, 18H, 6 × Ac) 1.150 (d, 3H, J = 6.2Hz, H-6b) 1.119, 1.083, 0.966, 0.864,
0.849 (5s, 15H, 5 × Me) 0.880 (d, 3H, J = 6.6Hz, Me) [Physical properties of compound 32α ] Rf = 0.37 (toluene: ethyl acetate = 2: 1) δ _H (CD ₃ OD, TMS) 5.364 (s, 1H, olefin hydrogen) 5.206 (s, 1H, H-1b) 4.407 (d, 1H, J = 7.4 Hz, H-1a)

[0043]

Example 4 Synthesis of Other Derivatives Synthesis of Rhaα1 → 2Galβ1 → 4Glc ( 2 + 40 → 41 → 42 → 43 ; FIG. 7) 2 + 40 → 41 Compound 2 (96 mg, 0.3 mmol), Compound 40 (172)
mg, 0.2 mmol), molecular sieve 4A 500 mg,
A mixture of 2 ml of 1.2-dichloroethane was stirred for 30 minutes under a stream of argon and then cooled to -10 ° C. A 1.2-dichloroethane solution of silver triflate (154 mg, 0.6 mmol) and phenylselenyl chloride (115 mg, 0.6 mmol) was sequentially added, and the mixture was stirred at -4 ° C for 30 minutes. The reaction solution was neutralized with triethylamine, diluted with chloroform, and filtered through Celite. After washing successively with saturated aqueous sodium hydrogen carbonate and saturated brine, the organic layer was dried over magnesium sulfate, and the solvent was evaporated. The residue was formed on a silica gel column (hexane: ethyl acetate = 4: 3), and 178 mg (7%) of trisaccharide 41 was added.
7.4%).

[Physical properties of compound 41 ] Rf = 0.40 (THF / hexane = 1: 2) [α] ²² _D −44.3 ° (C = 0.53, CHCl ₃ ). δ _H (CDCl ₃ , TMS) 7.40 to 7.09 (m, 30H, Aromatic proton) 5.420 (s, 1H, benzylidene proton) 5.2298 (dd, 1H, J = 1.8, 3. 3Hz, H-2
c) 5.196 (dd, 1H, J = 3.3, 9.9Hz, H-3
c) 5.180 (d, 1H, J = 1.8 Hz, H-1c) 4.450 (d, 1H, J = 7.7 Hz, H-1b) 4.445 (d, 1H, J = 7. 7Hz, H-1a) 1.999, 1.975, 1.964 (3s, 9H, 3
× Ac) 0.812 (d, 3H, J = 6.2 Hz, H-6c) 41 → 42 3 sugar 41 (36 mg, 0.031 mmol), 80% AcOH
2 ml of the mixture was stirred at 80 ° C. for 30 minutes. After the reaction solution was azeotropically distilled with toluene several times, the residue was produced with LH-20 (MeOH) to obtain a diol derivative 42 (32.5 mg, 98%).

[Physical Properties of Compound 42 ] Rf = [α] ²² _D −27.1 ° (C = 1.1, CHCl ₃ ). δ _H (CDCl ₃ , TMS) 7.42 to 7.18 (m, 25H, Aromatic proton) 5.288 (dd, 1H, J = 1.8, 3.6Hz, H-2
c) 5.210 (dd, 1H, J = 3.6, 10.2Hz, H-
3c) 5.190 (d, 1H, J = 1.8 Hz, H-1c) 4.924 (t-1H, J = 10.2 Hz, H-4c) 4.465 (d, 1H, J = 7. 7Hz, H-1b) 4.365 (d, 1H, J = 7.7Hz, H-1a) 4.182 (m, 1H, H-5c) 2.002, 1.985, 1.960 (3s, 9H, 3
4Ac) 0.836 (d, 3H, J = 6.2 Hz, H-6c) 42 → 43 Diol 42 (32 mg, 30 μmol), 20% Pd
(OH) ₂ -C (32 mg), MeOH-H ₂ O (4:
1) 2 ml of the mixture was catalytically reduced at room temperature for 20 hours. The catalyst was filtered off, the filtrate was concentrated under reduced pressure, and the residue was added with MeOH (3 m).
1, K ₂ CO ₃ (6.2 mg) was added, and the mixture was stirred at room temperature for 15 hours. The reaction solution was formed with LH-20 (MeOH) to obtain 13.7 mg (93%) of deprotected form 43 . (Α /
β = 2: 1) [Physical properties of compound 43 ] Rf = 0.17 (AcOEt: EtOH: H ₂ O = 5:
1: 1) δ _H (CD ₃ OD, TMS) 5.219 (d, 0.33H, J = 1.5Hz, H-1c)
β) 5.200 (d, 0.67H, J = 3.7Hz, H-1a
α) 4.967 (d, 0.67H, J = 1.5Hz, H-1c
α) 4.557 (d, 0.33H, J = 7.7Hz, H-1a
β) 4.365 (d, 0.67H, J = 7.3Hz, H-1b
α) 4.351 (d, 0.33H, J = 7.3Hz, H-1b
β) 1.249 (d, 2H, J = 6.2Hz, H-6cα) 1.232 (d, 1H, J = 6.2Hz, H-6cβ) Synthesis of Rhaα1 → 2Galβ1 → 4Glcβ1 → Cer ( 41 → 45 → 46 → 47 → 48 → 49; FIG. 7) 41 → 4 5 41 ( 460mg, 0.4mmol), 20% Pd (OH) 2
-C (200mg), MeOH-H 2 O (4: 1) A mixture of 5ml for 20 hours catalytic reduction at room temperature. After the catalyst was filtered off, the filtrate was distilled off under reduced pressure. 20 ml of pyridine, 20 ml of acetic anhydride and a catalytic amount of 4-dimethylaminopyridine were added to the residue, and the mixture was stirred at room temperature overnight. The solvent was distilled off, and the residue was azeotropically distilled with toluene several times, and the residue was purified by a silica gel column to give 45 (3
60 mg, 99%) was obtained (α: β = 5: 4).

[Physical Properties of Compound 45 ] Rf = 0.62 (chloroform: methanol = 40:
1) δ _H (CDCl ₃ ) 6.250 (d, 0.56H, J =
3.7 Hz, H-1aα 5.633 (d, 0.44H, J = 8.0 Hz, H-1a
β) 45 → 46 45 (301 mg, 0.33 mmol), hydrazine acetic acid (46 mg, 0.5 mmol), dimethylformamide 1.5
The ml mixture was stirred at room temperature for 1 hour. The reaction solution is LH-2
0 (methanol), followed by silica gel column purification (ethyl acetate: toluene = 4: 1) to give 46 (23
3 mg, 81%) was obtained.

[Physical Properties of Compound 46 ] Rf = 0.47 (ethyl acetate: toluene = 4: 1) A solution of 46 → 47 46 (93 mg, 107 μmol) in 1.2 ml of 1.2-dichloroethane was stirred under water cooling while stirring with trichloroacetonitrile (108 μl, 1.07 mmol), 1.8 diazabicyclo [5,4,0] undecene (32 μl, 214 μmol).
Were sequentially added and stirred overnight. The reaction solution was purified by silica gel column (ethyl acetate: toluene = 4: 1) 47 (103
mg, 95%) was obtained.

[Physical Properties of Compound 47 ] Rf = 0.61 (ethyl acetate: toluene = 4: 1) δ _H (CDCl ₃ , TMS) 8.737 (s, 1H, = NH ) 6.401 (d , 1H, J = 3.7Hz, H-1a) 5.533 (t, 1H, J = 9.9Hz, H-3a) 5.353 (d, 1H, J = 3.3Hz, H-4b) 5 200 (dd, 1H, J = 3.3, 9.9Hz, H-3
c) 5.123 (dd, 1H, J = 7.7, 10.2Hz, H-
2b) 4.953 (dd, 1H, J = 3.3, 10.2Hz, H-
3b) 4.882 (d, 1H, J = 1.2 Hz, H-1c) 4.515 (d, 1H, J = 7.7 Hz, H-1b) 3.815 (t, 1H, J = 9. 9 Hz, H-4a) 2.163, 2.149, 2.139, 2.101,
2.058, 2.034, 2.002, 1.967 x 2
(8s, 27H, 9xAc) 1.150 (d, 1H, J = 6.6Hz, H-6c)

[Chemical 7] 47 (43 mg, 42 μmol), 50 (48 mg, 64 μmo)
l), molecular sieve 4A (400 mg) and chloroform (1.5 ml) were stirred at room temperature for 30 minutes, and then-
The mixture was cooled to 20 ° C., boron trifluoroetherate (12 μmol, 131 μmol) was added, and the mixture was stirred for 40 minutes. The reaction mixture was neutralized with triethylamine, diluted with chloroform, filtered through Celite, and washed with saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over magnesium sulfate, the solvent was evaporated, and the residue was purified by silica gel column (toluene: acetone = 5: 1) to obtain 6.4 mg (9.4%) of 48 . In addition, as a decomposed product of 47 , 25 mg of 51 (68
%)Obtained.

[Physical Properties of Compound 48 ] Rf = 0.23 (toluene: acetone = 5: 1) [α] ²² _D −1.3 ° (C = 0.4, chloroform) δ _H (CDCl ₃ , TMS) ) 8.05 to 7.42 (m, 5H, Aromatic proton) 5.931 (d, 1H, J = 8.8Hz, NH) 5.864 (dt, 1H, J = 7.0, 15.0Hz, 5ce
r) 5.628 (t, 1H, J = 7.4Hz, 3cer) 5.484 (dd, 1H, J = 7.4, 15.0Hz, 4ce)
r) 5.343 (d, 1H, J = 3.3Hz, H-4b) 5.178 (dd, 1H, J = 2.9, 10.2Hz, H-
3c) 4.998 (d, 1H, J = 1.9Hz, H-1c) 4.937 (dd, 1H, J = 3.3, 10.3Hz, H-
3b) 4.466 (m, 1H, H-5c) 4.424 (d, 1H, J = 7.7Hz, H-1b) 4.374 (d, 1H, J = 7.7Hz, H-1a) 2.225, 2.151, 2.135, 2.068,
2.041, 2.014, 1.979, 1.956
1.950 (9s, 27H, 9xAc) 1.192 (d, 3H, J = 6.2Hz, H-6c) 0.879 (t, 6H, J = 7.0Hz, Mex2) [Compound Physical Properties of 51 ] RF = 0.17 (toluene: acetone = 5: 1) 48 → 49 48 (6 mg, 3.7 μmol), 0.5 ml of tetrahydrofuran / methanol (1/1) solution and 1N NaOH
The mixture (0.1 ml) was stirred at room temperature for 15 hours. LH-20 (chloroform: methanol: water = 6)
Purification at 0: 30: 5) provided 3.5 mg (83%) of 49 .

[Physical Properties of Compound 49 ] Rf = 0.59 (chloroform: methanol: water = 6)
0: 30: 5) δ _H (DMSOd ₆ : D ₂ O = 49: 1) 5.578 (dt, 1H, J = 7.4, 15.1Hz, 5ce
r) 5.346 (dd, 1H, J = 7.4, 15.4Hz, 4ce
r) 5.164 (s, 1H, H-1c) 4.289 (d, 1H, J = 7.7Hz, H-1b) 4.213 (d, 1H, J = 7.6Hz, H-1a) 1.120 (d, 3H, J = 5.8Hz, H-6c) 0.854 (t, 6H, J = 7.0Hz, Me × 2) Rhaα1 → 2Galβ1 → 4Glc The 1st hydroxyl group of glucose is fluorine. Synthesis of Fluoride Substituted with (FIG. 7) 51 → 52 51 (25 mg, 25 μmol), Methanol 1 ml and 1N
Mix a mixture of sodium methoxide (50 μl) at room temperature with 1
Stir for 8 hours. The reaction solution was purified by LH-20 (methanol) to obtain 11.7 mg (83%) of 52 .

[Physical Properties of Compound 52 ] Rf = 0.21 (chloroform: methanol: water = 6)
0: 30: 5) δ _H (CD ₃ OD, TMS) 5.194 (dd, 1H, J = 7.0, 53.2Hz, H-1a) 5.192 (s, 1H, H-1c) 4.361 ( d, 1H, J = 7.5 Hz, H-1b) 1.228 (d, 3H, J = 6.2 Hz, H-6c) NeuAc2 → 6Galβ1 → 4Rhaα1 → 2Gl
Synthesis of c (Fig. 8) Condensation reaction 55 + 42 → 56α + 56β Sialic acid donor 55 (24 mg, 46 μmol), trisaccharide acceptor 42 (32 mg, 30 μmol), molecular sieve 3A (500 mg) A mixture of 2 ml of acetonitrile at room temperature. After stirring for 2 hours, the mixture was cooled to -40 ° C, and a solution of silver triflate (29 mg, 113 µmol) in 0.5 ml of acetonitrile and phenylselenyl chloride (22 mg, 1
A solution of 15 .mu.mol) in 0.5 ml of acetonitrile was sequentially added. After stirring at this temperature for 1 hour, the reaction solution was neutralized with triethylamine, diluted with ethyl acetate, and filtered through Celite.
After washing successively with saturated aqueous sodium hydrogen carbonate and saturated brine, the organic layer was dried over magnesium sulfate, and the solvent was evaporated. The residue is SX-4
Gel filtration purification with (toluene) was performed to obtain 45 mg of a tetrasaccharide compound. Then, preparative TLC (ethyl acetate: toluene = 4: 1) was used to separate and generate the α-tetrasaccharide.
The body 56α 26mg (56.5%), the β body 56β 7.8
Obtained mg (17%).

[Physical Properties of Compound 56α ] Rf = 0.35 (ethyl acetate: toluene = 3: 1) [α] ²² _D −34.1 ° (C = 1.6, chloroform) δ _H (CDCl ₃ , TMS) 7.40 to 7.20 (m, 25H, aromatic hydrogen) 5.351 (m, 1H, H-8d) 5.273 (dd, 1H, J = 1.5, 3.3Hz, H-2
c) 5.197 (dd, 1H, J = 3.3, 10.2 Hz, H-
3c) 5.153 (s, 1H, H-1c) 4.902 (t, 1H, J = 10.2Hz, H-4c) 4.456 (d, 1H, J = 7.7Hz, H-1b) 4.416 (d, 1H, J = 8.1Hz, H-1a) 4.173 (m, 1H, H-5c) 2.473 (dd, 1H, J = 4.4, 12.8Hz, H- 3d
eq) 2.106, 2.102, 2.045, 1.988,
1.983, 1.959, 1.946, 1.891 (8
s, 24H, 8 × Ac) 0.820 (d, 3H, J = 6.2 Hz, H-6c) [Physical properties of compound 56β ] Rf = 0.45 (ethyl acetate: toluene = 3: 1) [α ] ²² _D −22.5 ° (C = 0.53, chloroform) δ _H (CDCl ₃ , TMS) 7.48 to 7.20 (m, 25H, Aromatic proton) 5.709 (d, 1H, J =) 9.5 Hz, NH ) 5.272 (dd, 1H, J = 1.5, 3.3 Hz, H-2
c) 5.170 (dd, 1H, J = 3.3, 10.1 Hz, H-
3c) 5.082 (s, 1H, H-1c) 4.449 (d, 1H, J = 7.7Hz, H-1b) 4.416 (d, 1H, J = 7.7Hz, H-1a) _{3.796 (s, 3H, -CO 2} Me) 2.502 (dd, 1H, J = 4.8,12.8Hz, H-3d
eq) 2.138, 2.045, 2.041, 2.033,
1.973, 1.969, 1.966, 1.867 (8
S, 24H, 8 × Ac) 0.807 (d, 3H, J = 6.2 Hz, H-6d) Acetylation of α-form 56α → 57α 56α (20 mg, 12.9 μmol), pyridine 1.5 m
After stirring a mixture of 1 ml and acetic anhydride (1.5 ml) at room temperature for 17 hours, the solvent was distilled off. The residue was purified by LH-20 (MeOH) to give 57α of 19 mg (93%).

[Physical properties of compound 57α] Rf = 0.33 (ethyl acetate: toluene = 3: 1) [α] ²² _D -33.3 ° (C = 1.26, chloroform) δ _H (CDCl ₃ , TMS) 7.40 to 7.20 (m, 25H, Aromatic proton) 5.488 (d, 1H, J = 1.8Hz, H-4b) 5.362 (ddd, 1H, J = 2.6, 4.9, 8.0Hz, H-
8d) 5.308 (dd, 1H, J = 1.5, 8.0 Hz, H-7
d) 5.279 (dd, 1H, J = 1.5, 3.3 Hz, H-2
c) 5.194 (dd, 1H, J = 3.3, 10.0Hz, H-3
c) 5.122 (s, 1H, H-1c) 4.895 (t, 1H, J = 10.0Hz, H-4c) 4.169 (m, 1H, H-5c) 3.755 (s, 3H, CO ₂ Me ) 2.545 (dd, 1H, J = 4.4, 12.8Hz, H-3d
eq) 2.103, 2.103, 2.027, 1.983,
1.983, 1.977, 1.977, 1.964,
1.885 (6S, 27H, 9 × Ac) 1.929 (t, 1H, J = 12.8Hz, H-3dax) 0.813 (s, 3H, J = 6.2Hz, H-6c) α-form Deprotection of 57α → 58α 57α (13 mg, 8.2 μmol), MeOH 1 ml, M
A mixture of eONa (5.2N, 10 μl) was added at room temperature to 1.
After stirring for 5 hours, 500 ml of water was added and the mixture was stirred overnight. The reaction solution was purified with LH-20 (MeOH), the solvent was distilled off, and the residue was added with MeOH-H ₂ O (4: 1) 7.5 ml, 20.
% Pd (OH) ₂ -C (18 mg) was added for catalytic reduction. The reaction solution was purified by LH-20 (MeOH), 5
6.1 mg (92%) of 8α was obtained.

[Physical Properties of Compound 58α ] Rf = 0.30 ( ⁿ BuOH: EtOH: H ₂ O = 2:
1: 1) δ _H (CD ₃ OD, TMS) 5.227 (br-s, 0.5H, H-1cβ) 5.181 (d, 0.5H, J = 3.7Hz, H-1a)
α) 5.010 (br-s, 0.5H, H-1cα) 4.564 (d, 0.5H, J = 8.1Hz, H-1a
β) 4.352 (d, 0.5H, J = 7.7Hz, H-1b
α) 4.317 (d, 0.5H, J = 7.7Hz, H-1b
β) 2.014, 2.010 (2s, 1H, Ac) 1.635 (t, 1H, J = 12.8Hz, H-3dax) 1.250 (d, 1.5H, J = 6.2Hz, H-6d
α) 1.233 (d, 1.5H, J = 6.2Hz, H-6d
β) NeuAcβ2 → 6Galβ1 → 4Rhaα1 → 2Gl
Synthesis of c 56β → 58β 56β (17 mg, 10.8 μmol), MeOH 1 ml,
A mixture of 0.1 N NaOH (0.5 ml) was stirred overnight at room temperature. Subjected to the same purification and 58α, 5.2 a 58β
mg (60%) was obtained (α / β = 2: 1).

[Physical Properties of Compound 58β ] Rf = 0.26 ( ⁿ BuOH: EtOH: H ₂ O = 2:
1: 2) δ _H (CD ₃ OD, TMS) 5.200 (d, 0.33H, J = 1.1Hz, H-1c)
β) 5.173 (d, 0.67H, J = 3.7Hz, H-1a
α) 4.990 (d, 0.67H, J = 1.1Hz, H-1c
α) 4.547 (d, 0.33H, J = 8.0Hz, H-1a
β) 4.294 (d, 0.67H, J = 7.7Hz, H-1b
α) 4.285 (d, 0.33H, J = 7.7Hz, H-1b
β) 2.798 (dd, 0.33H, J = 4.8, 12.1Hz, H-3deq
β) 2.771 (dd, 0.67H, J = 4.8, 12.1Hz, H-3deq
α) 1.678 (t, 0.33H, J = 12.1Hz, H-3dax
β) 1.674 (t, 0.67H, J = 12.1Hz, H-3dax
α) 1.242 (d, 2H, J = 6.2Hz, H-6cα) 1.222 (d, 1H, J = 6.2Hz, H-6cβ) Fucα1 → 2Glc, Fucα1 → 2Glc1 → C
er and Fucα1 → 2Glc → Oct (FIG. 9) (i) Fucα1 → 2Glc ( 60 + 61 → 62α)
→ 63α → 64 ) condensation reaction 60 + 61 → 62α + 62β 60 (0.78g, 1.45mmol), 61 (1.01)
g, 2.17 mmol), molecular sieve 4A (1.5
g), Silver triflate (1.12g, 4.36mm)
ol) and 4 ml of 1.2-dichloroethane were stirred at room temperature for 1 hour, cooled to -15 ° C, and added with 3 ml of a solution of phenylselenyl chloride in 1.2-dichloroethane,
Stir for minutes. The reaction solution was neutralized with triethylamine, filtered through Celite, and the filtrate was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over magnesium sulfate and the solvent was evaporated. The residue was purified with a silica gel column ( ^n- hexane: ethyl acetate = 4: 1) to obtain α-form 62α of 997 mg (72 mg ).
%), And β-form 62β was obtained in an amount of 301 mg (22%).

[Physical Properties of Compound 62α ] Rf = 0.44 ( ⁿ hexane: ethyl acetate = 4: 1) δ _H (CDCl ₃ , TMS) 7.42 to 7.02 (m, 35H, Aromatic proton) 5 .518 (d, 1H, J = 3.7 Hz, H-1b) 4.608 (d, 1H, J = 8.4 Hz, H-1a) 4.177 (q, 1H, J = 6.6 Hz, H -5b) 3.974 (dd, 1H, J = 3.7, 10.3Hz, H-
2b) 3.863 (t, 1H, J = 9.2Hz, H-2a) 3.846 (dd, 1H, J = 3.7, 10.3Hz, H-
3b) 3.793 (t, 1H, J = 9.1Hz, H-4a or H-3a) 3.683 (dd, 1H, J = 4.7, 11.0Hz, H-
6a) 3.621 (t, 1H, J = 9.1 Hz, H-3a or H-4a) 3.351 (br-s, 1H, H-4b) 0.782 (d, 3H, J = 6. 6 Hz, H-3b) [Physical properties of compound 62β ] Rf = 0.50 ( ⁿ hexane: ethyl acetate = 4: 1) δ _H (CDCl ₃ , TMS) 7.48 to 7.15 (m, 35H, Aromatic proton) 4.923 (d, 1H, J = 7.7 Hz, H-1b) 4.423 (d, 1H, J = 8.4 Hz, H-1a) 3.805 (dd, 1H, J = 7. 7,9.9Hz, H-2
b) 3.558 (d, 1H, J = 2.2 Hz, H-4b) 3.392 (q, 1H, J = 6.6 Hz, H-5b) 1.197 (d, 3H, J = 6. 6Hz, H-6b) Acetyl-substituted 62α → 63α 62α (987mg, 1.03mmol), 20% Pd (O
H) ₂ -C (560mg) and MeOH-H ₂ O (4:
1) 35 ml of the mixture was catalytically reduced for 16 hours at room temperature. The catalyst was filtered off, the filtrate was azeotroped with toluene several times, and 40 ml of pyridine, 40 ml of acetic anhydride and a catalytic amount of 4-DMAP were added to the residue.
(4-Dimethylaminopyridine) was added and stirred for 2 days. Toluene was added and the solvent was evaporated, and the residue was purified by silica gel column (toluene: ethyl acetate = 1: 1) 63
150 mg (24%) of α was obtained.

[Physical Properties of Compound 63α ] Rf = 0.29 (toluene: ethyl acetate = 1: 1) δ _H (CDCl ₃ , TMS) 6.301 (d, 1H, J = 4.0 Hz, H-1a) ) 5.441 (d, 1H, J = 9.9Hz, H-3a) 5.267 (d, 1H, J = 3.7Hz, H-1b) 5.251 (d, 1H, J = 3.3Hz) , H-4b) 5.204 (dd, 1H, J = 3.3, 11.0 Hz, H-
3b) 5.043 (t, 1H, J = 9.9Hz, H-4a) 4.979 (dd, 1H, J = 3.7, 11.0Hz, H-
2b) 4.304 (dd, 1H, J = 4.4, 12.5Hz, H-
6a) 4.165 (q, 1H, J = 6.6Hz, H-5b) 4.056 (dd, 1H, J = 2.2, 12.5Hz, H-
6a ') 4.024 (dd, 1H, J = 4.0, 9.9Hz, H-2
a) 2.238, 2.144, 2.085, 2.022x
3,1.973 (5s, 21H, 7xAc) 1.132 (d, 3H, J = 6.6Hz, H-6b) Deacetylation 63α → 64 63α (20mg, 32µmol ), 2ml of methanol and potassium carbonate The mixture of (9 mg, 64 μmol) was stirred at room temperature for 1 hour. The reaction solution was purified by LH-20 (methanol) to obtain 8.3 mg (79%) of 64 . (Α / β = 3:
1) [Physical Properties of Compound 64 ] δ _H (CD ₃ OD, TMS) 5.281 (d, 0.75H, J = 3.3Hz, H-1a)
α) 5.158 (br-s, 0.25H, H-1bβ) 4.949 (d, 0.75H, J = 4.0Hz, H-1b
α) 4.551 (d, 0.25H, J = 7.7Hz, H-1a
β) 4.295 (q, 0.25H, J = 6.6Hz, H-5b
β) 4.207 (q, 0.25H, J = 6.6Hz, H-5b
α) 1.191 (d, 3H, J = 6.6 Hz, H-6bβ) (ii) Synthesis of Fucα1 → 2Glc1 → Cer ( 63α →
65 → 68 → 69 ) Deacetylation of 1-position of glucose 63α → 65 63α , a mixture of 128 mg (0.206 mmol) hydrazine acetic acid (38.2 mg, 0.412 mmol) and DMF 2 ml was stirred at room temperature for 1 hour. After diluting with ethyl acetate, the extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over magnesium sulfate and the solvent was evaporated. The residue was purified with a silica gel column (toluene: ethyl acetate = 3: 1), and 65 was added to 9
Obtained 5.7 mg (80.2%).

[Physical Properties of Compound 65 ] Rf = 0.38 (toluene: ethyl acetate = 1: 1) δ _H (CDCl ₃ , TMS) 5.498 (t, 1H, J = 9.52 Hz, H-3a) ) 4.642 (q, 1H, J = 6.59Hz, H-5b) 2.157, 2.153, 2.094, 2.087,
2.045, 2.018, 2.012, 2.001,
1.987, 1.982 (12s, 36H, 12Ac) 1.135 (d, 1H, 6.59Hz) 1.112 (d, 1H, J = 6.59Hz) Imidization 65 → 95.7mg of 66 65 A solution of (0.165 mmol) in 1.2-dichloroethane (2 ml) was stirred at 0 ° C. into which 260 μl (15.6 eq) of trichloroacetonitrile, 1.8 were added.
-Diazabicyclo [5,4,0] undecene 18 μl
(0.7 eq) were added sequentially and stirred for 45 minutes. The reaction solution was purified with a silica gel column (toluene: ethyl acetate = 1: 1).
1) to give 94.7 mg (79.2%) of 66 .

[Physical Properties of Compound 66 ] Rf = 0.63 (toluene: ethyl acetate = 1: 1) [α] ²⁷ _D -10.463 (C = 1.0, CHCl ₃ ) δ _H (CDCl ₃ , TMS) 8.802 (s, 1H, NH ) 6.476 (d, 1H, J = 4.03Hz, H-1a) 5.527 (t, 1H, J = 9.52Hz, H-3a) 5 .3076 (d, 1H, J = 3.67 Hz, H-1b) 5.089 (t, 1H, J = 9.52 Hz, H-4a) 2.143, 2.076, 2.029, 2.026, 1.988, 1.957 (6s, 1
8H, 6Ac) 1.128 (d, 3H, J = 6.59 Hz, H-6b) Condensation reaction 66 + 50 → 68α + 68β 66 , 56.1 mg (0.078 mmol), 50 , 87.8.
While stirring a mixture of mg (0.116 mmol), CHCl ₃ 1.0 ml and molecular sieve 4A 800 mg at −15 ° C., BF ₃ OEt ₂ , 15 μl was added thereto,
Stir for 1.5 hours. After diluting with ethyl acetate, the mixture was filtered through Celite, and the filtrate was washed with saturated aqueous sodium hydrogen carbonate and saturated brine.
The organic layer was dried over magnesium sulfate and the solvent was evaporated.
Silica gel column purification of the residue (toluene: acetone =
8: 1) to give 68β 24 mg (23.5%), 68α
18 mg (19.6%) was obtained.

[Physical Properties of Compound 68 ] 68β Rf 0.53 (toluene: acetone = 5: 1) 68α Rf 0.64 (toluene: acetone = 5: 1) 68β [α] ²⁸ _D -13.6 (C = 1.0, CHC
l ₃ ) 68α [α] ²⁸ _D 2.38 (C = 0.5, CHC
l ₃ ) [Physical properties of compound 68β ] δ _H (CDCl ₃ , TMS) 5.896 (d, 1H, J = 7.69 Hz, NH ) 5.886 (d, t, 1H, J = 7.33 Hz, 15.39Hz, 5Cer) 5.641 (t, 1H, J = 7.33Hz, 3Cer) 5.497 (dd, 1H, J = 7.33Hz, 15.39Hz, 4Cer) 5.2298 (br-s, 1H, H- 1b) 5.217 (t, 1H, J = 9.16 Hz, H-3a) 4.916 (t, 1H, J = 9.89 Hz, H-4a) 4.440 (d, 1H, J = 7. 69Hz, H-1a) 4.403 (q, 1H, J = 6.23Hz, H-5b) 4.509 (dd, 1H, J = 5.13Hz, 12.45Hz, H-6a) 3.824 (dd, 1H, J = 4.4Hz, 10.99Hz, H-6a ') 2.150, 2.050, 2.016, 1.989, 1.981, 1.953 (6s, 18H,
6Ac) 1.124 (d, 3H, J = 6.6 Hz, H-6b) 0.877 (t, 6H, J = 6.96 Hz, 2Me) [Physical properties of compound 68α ] δ _H (CDCl ₃ , TMS ) 6.044 (dt, 1H, J = 6.96, 15.39Hz, 5Cer) 5.686 (t, 1H, J = 8.79, 3Cer) 5.228 (d, 1H, J = 4.03Hz, H-) 1b) 4.802 (d, 1H, J = 3.67Hz, H-1a) 4.181 (q, 1H, J = 6.6Hz, H-5b) 2.177,2.062,2.057,2.008,2.005 (6s, 18H, 6A
c) 0.996 (d, 3H, J = 6.59Hz, H-6b) 0.876 (t, 6H, J = 7.33Hz, 2Me) Deprotection 68β → 69β 68α → 69α 68β , 12.2mg ( 9.28 μmol) in MeOH: T
HF = (1: 1), dissolved in 1 ml, 1N NaOH solution 0.3 ml was added, and the mixture was stirred day and night. LH directly to the reaction solution
-20 column purification (chloroform: MeOH = 1: 2)
Then , 9.86 mg (100%) of 69β was obtained.

Similarly, 68α , 11.0 mg (8.37μ)
mol) in MeOH: THF (1: 1), 1 ml,
0.3 ml of 1N NaOH solution was added, and the mixture was stirred day and night. The reaction solution was purified by the same procedure to obtain 8.3 mg of 69α .
(93.3%) was obtained.

[Physical Properties of Compound 69 ] Rf 69β 0.50 (chloroform: MeOH =
5: 1) 69α 0.47 (chloroform: MeOH = 5:
1) 69β _H (CD ₃ OD, TMS) 5.701 (dt, 1H, J = 7.33Hz, 15.76Hz, 5Cer) 5.45112 (dd, 1H, J = 7.7Hz, 15.76Hz, 4Cer) 5.066 (Br-s, 1H, J = 7.69Hz, H-1a) 4.345 (d, 1H, J = 7.69Hz, H-1a) 0.883 (t, 6H, J = 6.94Hz, 2Me) [Physical Properties of Compound 69α ] δ _H (CD ₃ OD, TMS) 5.719 (dt, 1H, J = 7.09Hz, 15.39Hz, 5Cer) 5.459 (dd, 1H, J = 7.32Hz, 15.29Hz, 4Cer) 4.944 (d, 1H, J = 1.47Hz, H-1b) 4.913 (d, 1H, J = 3.3Hz, Ha) 1.212 (d, 3H, J = 6. 6Hz, H-6b) 0.897 (t, 6H, J = 7.33Hz, 2Me) (iii) Synthesis of Fucα1 → 2Glc → Oct Condensation reaction 66 + 70 → 71 66 , 38.6 mg (0.053 mmol), 70 ( ⁿ octanol) , 17 μmol (0.107 mmol), 1.0 ml of dichloroethane, and 400 mg of molecular sieve 4A were stirred at −15 ° C., and 11 μl of BF ₃ OEt ₂ was added thereto, which was stirred for 3 hours. Then, the mixture was diluted with ethyl acetate, filtered through Celite, and the filtrate was washed with saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over magnesium sulfate and the solvent was distilled off. The residue was purified by LH-20 column (chloroform: MeOH = 1: 1) to give 71 as 29.2 mg.
(79.2%) was obtained.

[Physical Properties of Compound 71 ] Rf 0.49 (toluene: acetone 5: 1) [α] ²⁶ _D -79.8 (C = 1.0, CHCl ₃ ) δ _H (CDCl ₃ , TMS) 5 .221 (d, 1H, J = 3.3 Hz, H-1b) 5.189 (d, 1H, J = 3.3 Hz, H-4b) 5.178 (t, 1H, J = 9.52 Hz, H -3a) 4.941 (dd, 1H, J = 4.03Hz, 10.99Hz, H-2b or H-3
b) 4.872 (t, 1H, J = 9.8Hz, H-4a) 4.511 (q, 1H, J = 6.6Hz, H-5b) 4.385 (d, 1H, J = 7. 69Hz, H-1a) 4.198 (dd, 1H, J = 4.77Hz, 12.09Hz, H-6a) 4.024 (dd, 1H, J = 2.2Hz, 12.09Hz, H-6a ') 3.731 (Dd, 1H, J = 7.7Hz, 7.16Hz, H-2a) 2.077, 2.001, 1.962, 1.925, 1.916, 1.908 (6s, 18H,
6Ac) 1.022 (d, 3H, J = 6.59 Hz, H-6b) 0.804 (t, 3H, J = 6.96 Hz, Me) Deprotection 71 → 72 71 , 29.2 mg (0.042 mmol ) To MeOH: T
It was dissolved in 1 ml of HF = 1: 1 solution, 0.3 ml of 1N NaOH solution was added, and the mixture was stirred for 2 hours. Directly add the reaction mixture to L
H-20 column purification (chloroform: MeOH = 1: 1)
2) to give 18.5 mg (100%) of 72 .

[Physical Properties of Compound 72 ] Rf 0.23 (chloroform: MeOH = 5: 1) δ _H (CD ₃ OD, TMS) 5.204 (br-s, 1H, H-1b) 4.343 ( d, 1H, J = 7.69Hz, H-1a) 4.279 (q, 1H, J = 6.6Hz, H-5b) 1.177 (d, 3H, J = 6.59Hz, H-6b) 0.887 (t, 3H, J = 6.96Hz, Me) Rhaα1-4Glcβ1-Pro, Rhaα1-6
Glcβ1-Pro, Rhaα1-4 (Rhaα1-
6) Glcβ1-Pro and Rhaα1-6Glcβ1
Synthesis of -All (Fig. 10) (i) Synthesis of Rhaα1-6Glcβ1-Pro Glycosylation 2 + 75 → 76a + 76b + 76c 75 (110 mg, 275 μmol), 2 (126 mg, 39
A mixture of 3 .mu.mol), molecular sieve 4A (1.4 g) and 4 ml of 1.2-dichloroethane was stirred at room temperature for 30 minutes and then cooled to -15.degree. Methyl triflate (6
7 μl, 592 μmol) was added and stirred for 1.5 hours.
The reaction solution was neutralized with triethylamine, diluted with chloroform, and filtered through Celite. The filtrate was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, the organic layer was dried over magnesium sulfate, and the solvent was evaporated. The residue was purified by a silica gel column to obtain 80 mg (43%) of α1 → 6 body 76a , (α1 → 6)
6,4) body 76b 22 mg (8.3%), α1 → 4 body 7
9 mg (5%) of 6c was obtained.

[Physical properties of α1 → 6 body 76a ] Rf = 0.56 ( ⁿ hexane: ethyl acetate = 3: 2) [α] ²² _D δ _H (CDCl ₃ , TMS) 7.38 to 7.22 (m, 10H, Aromatic pro
ton) 5.947 (m, 1H, -OCH 2 C H CH 2) 5.288 (dd, 1H, J = 3.3, 9.5Hz, H-3b) 5.279 (br-s, 1H, H-2b) 5.056 (t, 1H , J = 9.5Hz, H-4b) 4.811 (br-s, 1H, H-2b) 4.472 (d, 1H, J = 7.3Hz, H-1a) 2.136, 2.044, 1.984 (3s, 9H, 3 × Ac ) 1.206 (d, 3H, J = 6.2Hz, H-6b) [Physical properties of α1 → 6,4 body 76b ] Rf = 0.37 ( ⁿ hexane: ethyl acetate = 3: 2) [α] ²² _D − 37.6 ° (c = 0.96, chloroform) δ _H (CDCl ₃ , TMS) 7.40 to 7.21 (m, 10H, Aromatic pro
ton) 5.264 (dd, 1H, J = 3.3, 9.9Hz, H-3b or H-3c) 5.226 (dd, 1H, J = 3.3, 9.9Hz, H-3c or H-3b) 5.188 (dd, 1H, J = 1.5, 3.3Hz, H-2b or H-2c) 5.085 (dd, 1H, J = 1.9, 3.3Hz, H-2c or H-2b) 5.046 (t, 1H, J = 9.9Hz, H-4b or H-4c) 4.995 (t, 1H, J = 9.9Hz, H-4c or H-4b) 4.928 (br-s, 1H, H-1b or H-1c) 4.812 (br-s, 1H, H- 1c or H-1b) 4.480 (d, 1H, J = 7.3Hz, H-1a) 2.126, 2.099, 2.055, 1.991, 1.986, 1.972 (6s, 18H,
6 × Ac) 1.213 (d, 3H, J = 6.2Hz H-6c) 0.812 (d, 3H, J = 6.2Hz H-6b) [Physical properties of α1 → 4 body 76c ] Rf = 0.30 ( ⁿ hexane : Ethyl acetate = 3: 2) [α] ²² _D −29.6 ° (c = 0.53, chloroform) δ _H (CDCl ₃ , TMS) 7.40 to 7.22 (m, 10H, Aromatic pro
ton) 5.951 (m, 1H, -OCH 2 C H CH 2) 5.223 (dd, 1H, J = 3.3, 10.3Hz, H-3b) 5.167 (dd, 1H, J = 1.0, 3.3Hz, H-2b) 5.061 (d, 1H, J = 1.0Hz, H-1b) 4.514 (d, 1H, J = 7.7Hz, H-1a) 4.022 (m, 1H, H-5b) 2.115, 1.995, 1.975 (3s, 9H, 3 × Ac) 0.770 (D, 3H, J = 6.2Hz, H-6b) Acetylation (production of Rhaα1-6Glcβ1-All) 76a → 78 76a (11 mg, 16.4 μmol), pyridine 0.5 m
A mixture of 1, 0.5 ml of acetic anhydride and a catalytic amount of 4-dimethylacinopyridine was stirred at room temperature for 4 hours, and the solvent was azeotropically distilled with toluene. The residue was purified by silica gel column ( ^n-
Hexane: ethyl acetate = 5: 4), 11 mg of 78 (94)
%)Obtained.

[Physical Properties of Compound 78 ] Rf = 0.51 ( ⁿ hexane: ethyl acetate = 5: 4) [α] ²² _D −48 ° (c = 0.75, chloroform) δ _H (CDCl ₃ , TMS) ) 7.39~7.21 (m, 10H, Aromatic proton) 5.940 (m, 1H, -OCH 2 C H CH 2) 5.049 (t, 1H, J = 9.9Hz, H-4b) 4.848 (t, 1H, J = 9.1 Hz, H-4a) 4.475 (d, 1H, J = 7.7 Hz, H-1a) 3.844 (m, 1H, H-5b) 3. 600 (t, 1H, J = 9.2Hz, H-2a or H-3a) 3.489 (dd, 1H, J = 8.0, 9.1Hz, H-3a or H-2a) 2.131, 2.038 , 1.980, 1.937 (4
s, 12H, 4 × Ac) 1.205 (d, 3H, J = 6.2 Hz, H-6b) Deprotection (production of Rhaα1-6Glcβ1-Pro) 76a → 77a 76a (30 mg, 44 μmol), 20% Pd (OH) ₂
A mixture of -C (20 mg) and 2 ml of methanol-water (4: 1) was catalytically reduced at room temperature for 2.5 hours. The catalyst is filtered off,
The filtrate was evaporated under reduced pressure, methanol (1 ml) and potassium carbonate (7 mg) were added to the residue, and the mixture was stirred at room temperature for 2 hours. The reaction solution was purified by LH-20 (methanol) to give 77a 1.
Obtained 5.2 mg (93%).

[Physical Properties of Compound 77a ] Rf = 0.56 ( ^n- butanol: ethanol: water = 2:
1: 1) δ _H (CD ₃ OD, TMS) 4.749 (br-s, 1H, H-1b) 4.232 (d, 1H, J = 7.7 Hz, H-1a) 1.261 (d , 3H, J = 6.0 Hz, H-6b) 0.950 (t, 3H, J = 7.3 Hz, Me) Deprotection (generation of Rhaα1-4Glcβ1-Pro) 76c → 77c 76c , (7.2 mg10. 7 μmol) deprotection of 76a
Was carried out in the same manner as in the above deprotection to obtain 77c (3.4 mg, 86%).

[Physical Properties of Compound 77c ] Rf = 0.54 ( ^n- butanol: ethanol: water = 2:
1: 1) δ _H (CD ₃ OD, TMS) 4.265 (d, 1H, J = 7.3 Hz, H-1a) 1.265 (d, 3H, J = 6.2 Hz, H-6b) 0 .945 (t, 3H, J = 7.3 Hz, Me) Deprotection (Rhaα1-4Rhaα1-6Glcβ1-P
generation of ro) 76b → 77b 76b (14mg , the de-protection of 14.8μmol), 76a
Was carried out in the same manner as the deprotection of 7b to obtain 6 mg (79%) of 77b .

[Physical Properties of Compound 77b ] Rf = 0.39 ( ^n- butanol: ethanol: water = 2:
1: 1) δ _H (CD ₃ OD, TMS) 4.812 (br-s, H-1b or H-1c) 4.246 (d, 1H, J = 8.0 Hz, H-1a) 1.260 (D, 3H, J = 6.2Hz, H-6b or H-6c) 1.257 (d, 3H, J = 6.2Hz, H-6c or H-6b) 0.948 (t, 3H, J = 7.3 Hz, Me) Synthesis of Glcβ1-naringenin (FIG. 11) Glycosylation 81 + 82 → 83 82 , 100 mg (367.2 μmol) and NaH52.9.
mg (containing 60%, 3.6 eq) was dissolved in 3 ml of DMSO, stirred at room temperature for 15 minutes, and then dissolved in 3 ml of DMSO 8
1, added 755.5mg (5eq), and stirred for 1.5 hours. After pouring the reaction solution into a 1N-HCl solution to make it acidic,
Extract with AcOEt, wash with water and brine, M
It was dried over gSO ₄ . The concentrated residue was subjected to silica gel column chromatography (PhMe: AcOEt: AcOH = 5:
1: 0.05), and 67.1 mg (30.3) of 83
%)Obtained.

[Physical properties of compound 83 ] ¹ H-NMR (acetone-d6, TMS) δ = 2.788 (1H, dd, J = 3.0,17.0 Hz,
H-3a) 3.262 (0.5H, dd, J = 13.0, 17.0H)
z, H-3b) 3.273 (0.5H, dd, J = 13.0, 17.5H)
z, H-3b) 4.16-4.30 (3H, m, H-5Glc, H-6aG
lc, H-6bGlc) 5.104 (0.5H, t, J = 9.5Hz, H-4Glc
) 5.107 (0.5H, t, J = 9.5Hz, H-4Glc
) 5.198 (0.5H, dd, J = 8.0, 9.5Hz, H
-2Glc) 5.199 (0.5H, dd, J = 8.0, 9.5Hz, H
-2Glc) 5.400 (0.5H, t, J = 9.5Hz, H-3Glc
) 5.402 (0.5H, t, J = 9.5Hz, H-3Glc
) 5.509 (0.5H, dd, J = 2.5, 13.5Hz,
H-2Glc) 5.506 (0.5H, dd, J = 2.5, 13.5Hz,
H-2Glc) 5.532 (0.5H, d, J = 8.0Hz, H-1Glc)
) 5.546 (0.5H, d, J = 8.0Hz, H-1Glc
) 6.144 (1H, d, J = 2.0Hz, H-6 or H-
8) 6.181 (1H, dd, J = 1.0, 2.0 Hz, H-8
or H-6) 6.906 (2H, d, J = 8.0Hz, H-2 ', H-6' or
H-3 ', H-5') 7.397 (2H, d, J = 8.5Hz, H-3 ', H-5' or
H-2 ', H-6') 8.709 (1H, s, OH-4 ') 12.061 (0.5H, s, OH-5) 12.073 (0.5H, s, OH-5) ) Deprotection (formation of Glcβ1-naringenin) 83 → 84 83 , 26.8 mg (44.5 μmol) was added to MeOH (1 m
l), 28% NaOMe-MeOH solution 3.6
μml (4/10 eq) was added, and the mixture was stirred at room temperature for 7 hours. Neutralize with Amberlyst 15 to remove resin, concentrate residue to LH-
20 purified by gel chromatography (MeOH), 84
Was obtained in an amount of 13.7 mg (70.1%).

[Physical Properties of Compound 84 ] ¹ H-NMR (CD ₃ OD, TMS) δ = 2.743 (0.5H, dd, J = 3.5,17.0)
Hz, H-3a) 2.750 (0.5H, dd, J = 3.5, 17.0Hz,
H-3a) 3.159 (0.5H, dd, J = 13.0, 17.0H)
z, H-3b) 3.161 (0.5H, dd, J = 13.0, 17.0H
z, H-3b) 4.964 (0.5H, d, J = 7.0Hz, H-1Glc
) 4.975 (0.5H, d, J = 7.0Hz, H-1Glc
) 5.373 (0.5H, dd, J = 2.5, 13.0Hz,
H-2) 5.378 (0.5H, dd, J = 2.5, 13.0Hz,
H-2) 6.18-6.21 (2H, m, H-6 and H-8) 6.820 (2H, d, J = 8.5Hz, H-2 ', H-6' or
H-3 ', H-5') 7.186 (2H, d, J = 8.5Hz, H-3 ', H-5' or
H-2 ′, H-6 ′) Synthesis of Glc2Acβ1-naringenin (FIG. 12) Ring-opening acetylation 85 → 86 85 1.083 g (1.73 mmol) of AcOH9m
It was dissolved in 1 ml of H ₂ O and stirred at room temperature for 1 hour. After distilling off the solvent, 5 ml of Ac ₂ O and 5 ml of pyridine were added,
Stirred at room temperature for 16 hours. After the solvent was distilled off, a large amount of water was added, the mixture was extracted with AcOEt, washed with a saturated saline solution, and dried with MgSO ₄ . The concentrated residue is subjected to silica gel column chromatography (PhMe: AcOEt = 3: 1).
The product was purified by 86 to obtain 868.8 mg (95.0%) of 86 .

[Physical Properties of Compound 86 ] ¹ H-NMR (CDCl ₃ , TMS) δ = 3.666 (0.83H, dd, J = 1.5, 11.
0Hz, H-6) 3.759 (0.83H, dd, J = 3.5, 11.0H
z, H-6 ') 3.810 (0.83H, t, J = 9.5Hz, H-4o
r H-3) 3.908 (0.83H, ddd, J = 1.5, 3.5, 10.0H
z, H-5) 3.984 (0.83H, t, J = 9.5Hz, H-3o)
r H-4) 4.492 (0.83H, d, J = 12.5Hz, CH ₂
Ph) 4.510 (0.83H, d, J = 10.5Hz, CH ₂
Ph) 4.618 (0.83H, d, J = 12.0Hz, CH ₂
Ph) 4.748 (0.83H, d, J = 11.5Hz, CH ₂
Ph) 4.815 (0.83H, d, J = 10.5Hz, CH ₂
Ph) 4.830 (0.83H, d, J = 12.0Hz, CH ₂
Ph) 5.050 (0.83H, dd, J = 3.5, 10.0H
z, H-2) 5.608 (0.17H, d, J = 8.0Hz, H-1
β) 6.294 (0.83H, d, J = 3.5Hz, H-1
α) 7.14-7.38 (15H, m, Ph) Bromination 86 → 87 86 503.9 mg (942.6 μmol) of CH ₂ C
l ₂ dissolved in 0.5 ml, Ac ₂ O 0.5 ml, 30% H
Br-AcOH 281.6 μl (1.5 eq) was added,
The mixture was stirred at 0 ° C for 1.5 hours. Add a large amount of water and add AcOE
After extraction with t, NaHCO ₃ aq, washed with brine, dried over MgSO _4, the solvent was distilled off, 87 52
Obtained 9.9 mg (101.2%).

[Physical Properties of Compound 87 ] ¹ H-NMR (CDCl ₃ , TMS) δ = 6.651 (1H, d, J = 4.0 Hz, H-1) Glycosylation 82 + 87 → 88 82 51. 9 mg (190.6 μmol), NaH22.
9 mg (60% content, 3 eq) was dissolved in 2.0 ml of DMSO, stirred for 15 minutes, and then dissolved in 1.0 ml of DMSO 87
529.9 mg (5 eq) was added, and the mixture was stirred at room temperature for 4.5 hours. After acidification with 1N-HCl, extraction with AcOEt, washing with NaHCO ₃ aq, saturated saline, and then Mg
Dried with SO ₄ . The concentrated residue was subjected to silica gel column chromatography (PhMe: AcOEt: AcOH = 5:
1: 0.05), 88 13.4 mg (9.4%)
Obtained.

[Physical properties of compound 88 ] ¹ H-NMR (acetone-d6, TMS) δ = 2.785 (0.5H, ddd, J = 2.0, 3.0, 17.0)
Hz, H-3a) 2.967 (0.5H, dd, J = 3.0, 17.0Hz,
H-3a) 3.245 (0.5H, ddd, J = 2.0, 3.0, 17.0Hz,
H-3b) 3.333 (0.5H, dd, J = 13.0, 17.0H)
z, H-3b) 3.906 (1H, t, J = 9.5Hz, H-3Glc) 5.158 (1H, dd, J = 8.0, 9.5Hz, H-2
Glc) 5.336 (0.5H, d, J = 8.0Hz, H-1Glc
) 5.352 (0.5H, d, J = 8.0Hz, H-1Glc
) 5.501 (0.5H, br.d, J = 11.5Hz, H-
2) 5.676 (0.5H, dd, J = 3.0, 13.0Hz,
H-2) 6.15 (2H, m, H-6 and H-8) 6.91 (2H, m, H-2 ', H-6' or H-3 ', H-5') 8. 550 (1H, br.s, OH-4 ′) debenzylation (production of Glc2Acβ1-naringenin) 88 → 89 88 9.9 mg of MeOH 0.8 ml, H ₂ O 0.2
It was dissolved in ml, 20% Pd (OH) ₂ -C 10 mg was added, and the mixture was stirred under H ₂ atmosphere for 3 hours. 20% P by filtration
The d (OH) _2- C was removed and the concentrated residue was purified by LH-20 gel chromatography (MeOH) to give 89 5.8 mg (91.8%).

[Physical Properties of Compound 89 ] ¹ H-NMR (Acetone-d6, TMS) δ = 2.027 (1.5H, s, Ac) 2.029 (1.5H, s, Ac) 4.978 (1H, dd, J = 8.0, 9.0Hz, H-2
Glc) 5.258 (0.5H, d, J = 8.0Hz, H-1Glc
) 5.277 (0.5H, d, J = 8.0Hz, H-1Glc
) 5.501 (1H, td, J = 3.0, 13.5Hz, H-
2) 6.117 (2H, m, H-6 and H-8) 8.013 (0.5H, br.s, OH-4 ') 8.618 (0.5H, br.s, OH-4) ′) 12.068 (0.5H, s, OH-5) 12.076 (0.5H, s, OH-5) Rhaα1-3Glcβ1-All and Rhaα1-
Synthesis of 3 (Rhaα1-2) Glcβ1-All (Fig. 1
3) (i) Rhaα1-3 (Rhaα1-2) Glcβ1-A
Synthesis of ll 90 + 2 → 91 1) 90, 106.91mg (0.35mmol), 2, 14
4.4 mg (0.45 mmol), dichloroethane (1.5 ml) and molecular sieves 4A (500 mg) were stirred at -15 ° C to give MeOTf (methyl triflate) (47.1 µl).
(0.42 mmol) was added, and the mixture was stirred day and night. After diluting with ethyl acetate, the mixture was filtered through Celite, and the filtrate was washed with saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over magnesium sulfate, the solvent was evaporated, and the residue was purified by silica gel column (toluene: ethyl acetate = 5: 1) to give 91 to 34.
Obtained 8 mg (17.3%).

90 + 95 → 91 + 96 2) 90 , 56.8 mg (0.18 mmol), 95 , 70 mg
(0.24 mmol), dichloroethane (1 ml) and molecular sieve 4A (300 mg) were stirred at -15 ° C, and hafnocene dichloride (139.8 mg, 0.37 mm) was added thereto.
ol) and silver trifluoromethanesulfonate 18
9.3 mg (0.74 mmol) was added, and the mixture was stirred day and night. After diluting with ethyl acetate, the mixture was filtered through Celite, and the filtrate was washed with saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over magnesium sulfate, the solvent was evaporated, the residue was purified by SX-8 (toluene) column, and 91 was 37.4% and 96 was 4
Obtained in 8.6%.

[0077] [Physical properties of the compound 91] Rf = 0.29 (toluene: ethyl acetate _{= 3: 2) δ H (} CDCl 3, TMS) 5.918 (m, 1H, -OCH 2 C H CH 2) 5.556 (s , 1H, benzylidene hydrogen) 5.337 (dd, 1H, J = 1.83Hz, 3.67Hz, H-2b) 5.297 (dd, 1H, J = 3.67Hz, 10.26Hz, H-3b) 5.200 (d, 1H, J = 1.83Hz, H-1b) 4.973 (t, 1H, J = 9.89Hz, H-4b) 4.404 (d, 1H, J = 7.7Hz, H-1a) 4.355 (dd, 1H, J = 5.13Hz, 10.99Hz , H-6a) 4.193 (dd, 1H, J = 5.87Hz, 9.9Hz, H-6a ') 3.884 (t, 1H, J = 9.16Hz, H-3a) 3.799 (t, 1H, J = 10.25Hz, H-4a) 3.621 (dd, 1H, J = 7.7Hz, 9.2Hz H-2a) 2.126, 1.974, 1.954 (3s, 9H, 3Ac) 0.8493 (d, 3H, J = 6.23Hz, H-6b) [Compound physical properties of the 96] Rf = 0.35 (toluene: ethyl acetate _{= 3: 2) δ H (} CDCl 3, TMS) 5.944 (m, 1H, -OCH 2 C H CH 2) 5.501 (s, 1H, benzylidene hydrogen ) 5.035 (d d, 1H, J = 9.89Hz, H-4b or H-4c) 4.958 (d, 1H, J = 1.1Hz, H-1b or H-1c) 4.873 (d, 1H, J = 1.1Hz, H-1c or H-1b) 4.865 (t, 1H, J = 9.9Hz, H-4b or H-4c) 4.514 (d, 1H, J = 7.67Hz, H-1a) 2.094, 2.072, 2.026, 1.953, 1.931, 1.902 (6s, 18H,
6Ac) 1.156 (d, 3H, J = 6.23Hz, H-6b) 0.564 (d, 3H, J = 6.23Hz, H-6c) 91 → 91' 91, 8mg (0.0138mmol), pyridine 1ml and acetic anhydride 1 ml of the mixture was stirred at room temperature for 1.5 hours. After distilling off the reaction solution, LH-20 column purification (chloroform: methanol = 1: 1) was carried out, and 91 ' , 8.59 mg
(100%) was obtained.

[0078] [Physical properties of the compounds 91'] Rf = 0.33 (toluene: ethyl acetate = (3: 1)) δ H (CD 3 OD, TMS) 5.833 (m, 1H, -OCH 2 C H CH ₂ ) 5.554 (s, 1H, benzylidene hydrogen) 5.088 (dd, 1H, J = 8.06Hz, 9.16Hz, H-2a) 4.932 (t, 1H, J = 9.89Hz, H- 4b) 4.511 (d, 1H, J = 8.06Hz, H-1a) 2.131, 2.104, 1.982, 1.959 (4s, 12H, 4Ac) 0.666 (d, 1H, J = 6.23Hz, H- 6b) 96 → 97 96 , 274 mg (0.032 mmol) in 80% acetic acid solution 2
ml was added and the mixture was stirred on an oil bath at 80 ° C. for 2 hours. The solution was azeotroped with toluene, evaporated, and purified by LH-20 column (chloroform: MeOH = 1: 1) to give 97 15.7 mg.
(63.9%) was obtained.

[0079] [Physical properties of the compound 97] Rf = 0.401 (toluene: ethyl acetate _{= 1: 2) δ H (} CDCl 3, TMS) 5.940 (m, 1H, -OCH 2 C H CH 2) 5 0.073 (d, 1H, J = 1.46Hz, H-1b or H-1c) 4.957 (d, 1H, J = 1.84Hz, H-1b or H-1c) 2.139, 2.11, 2.043, 2.030, 1.977 , 1.970 (6s, 18H,
6Ac) 1.256 (d, 3H, J = 6.6Hz, H-6b or H-6c) 1.153 (d, 3H, J = 6.22Hz, H-6b or H-6c) 97 → 98 97 , 30mg MeOH (1 ml) and Na (0.039 mmol)
0.05 ml of OMe was added and the mixture was stirred day and night. It was treated with Amberlyst 15E and the solvent was distilled off. LH the residue
-20 column refinement (MeOH), 98 19.6mg
(97.5%) was obtained.

[Physical Properties of Compound 98 ] Rf = 0.50 (BuOH: EtOH: H ₂ O = 2:
_{1: 1) δ H (CD} 3 OD, TMS) 5.979 (m, 1H, -OCH 2 C H CH 2) 4.944 (d, 1H, J = 1.46Hz, H-1b or H-1c) 4.901 (d, 1H, J = 1.47Hz, H-1b or H-1c) 4.414 (d, 1H, J = 8.06Hz, H-1a) 1.263 (d, 3H, J = 6.23) Hz, H-6b or H-6c) 1.205 (d, 3H, J = 5.87Hz, H-6b or H-6c) (ii) Synthesis of Rhaα1-3Glcβ1-All 91 → 92 91 , 23.4 mg ( 80% acetic acid solution was added to 0.040 mmol), and the mixture was stirred on an oil bath at 80 ° C. for 2 hours. The solution was azeotropically distilled with toluene and purified by LH-20 column (chloroform: MeOH = 20: 1) to give 92 (13.0 mg).
(65.5%) was obtained.

[0081] [Physical properties of the compound 92] Rf = 0.30 (toluene: ethyl acetate _{= 1: 2) δ H (} CDCl 3, TMS) 5.926 (m, 1H, -OCH 2 C H CH 2) 5 .370 (dd, 1H, J = 1.83Hz, 3.3Hz, H-2b) 5.129 (d, 1H, J = 1.83Hz, H-1b) 5.083 (t, 1H, J = 9.89Hz, H-4b) 4.364 (d, 1H, J = 7.7Hz, H-1a) 3.569 (t, 1H, J = 8.79Hz, H-3a) 2.505, 2.050, 1.997 (3s, 9H, 3Ac) 1.245 (d, 3H, J = 6.25 Hz, H-6b) 92 → 93 92 , 35.6 mg (0.072 mmol) in MeOH 2 ml,
0.05 ml of NaOMe was added and stirred for 7 hours. It was treated with Amberlyst 15E and the solvent was distilled off. The residue was subjected to LH-20 column purification (MeOH) to obtain 26.5 mg (100%) of 93 .

[Physical Properties of Compound 93] Rf = 0.66 (BuOH: EtOH: H ₂ O = 2:
_{1: 1) δ H (CD} 3 OD, TMS) 5.959 (m, 1H, -OCH 2 C H CH 2) 5.154 (br-s, 1H, H-1b) 4.312 (d, 1H , J = 8.06 Hz, H-1a) 3.492 (t, 1H, J = 9.16 Hz, H-3a) 3.401 (t, 1H, J = 9.53 Hz, H-4a) 1.252 (D, 3H, J = 6.23 Hz, H-6b) The starting materials were obtained based on the following documents.

Compound 1 : K. Takeo and Y. Suzuki, Carbo
hydr. Res., 162 , 95 (1987). 2 : L.Andras, S.Lajos, H.Janos, J.Carbohydr.chem., 7
(3) 687-699 (1988) 3 : Rhaα1 → 2Glc (neohesperidose) S.Kamiya, S.Esaki, M.Hama, Agric.Biol.chem., 31 (3) , 26
1-266 (1967) (II) Action as anti-inflammatory agent The evaluation method and results of the effect of the above compound as an anti-inflammatory agent are shown below.

(1) Experimental Animals Male Hartley guinea pigs weighing 200 to 250 g were used.

(2) Experimental Materials Antiserum was anti-ovalbumin rabbit serum (anti-count = 1/80)
000), and ovalbumin was used as the antigen.

(3) Experimental method The passive Arthus reaction was performed by the method of Katayama et al. [Kataya].
ma, S.M. et al. , Arzein-Forsc
h. , 31 , 1196 (1981)].
That is, 2.5m of anti-ovalbumin rabbit serum in guinea pig
Sensitization was carried out by intravenously administering 1 / kg. Part 3
After 0 minutes, 0.0 mg of antigen solution containing 0.1 mg of ovalbumin
5 ml was intradermally administered to the abdomen that had been shaved on the previous day to induce a reaction. Two hours after the antigen challenge, the area of bleeding at the stimulation site was measured and used as an index of the degree of reaction. Also,
The test drug was intravenously administered 30 minutes before the antigen administration. There were 4 guinea pigs in each group.

(4) Experimental Results Table 1 shows the bleeding area at the stimulation site when each compound was administered. The figures are 100% for the saline administration group.
Is calculated as the suppression rate. From the results shown in Table 1, the inhibitory effect was observed for all the compounds tested.

[0088]

[Table 1] (5) Judgment From the results of the Arthus reaction, it is clear that the compound has a type III allergy suppressing effect.

[Brief description of drawings]

FIG. 1 is a flow chart showing a synthetic route for an imidate compound, which is a synthetic intermediate for a 1-substituted neohesperidose derivative.

FIG. 2 shows a synthetic intermediate (imidate) to Rhaα1-
It is a flowchart which shows the path | route which synthesize | combines the pathway which synthesize | combines 2Glc-Oct, and the 1-position of neohesperidose with the fluorine substitution product.

FIG. 3 shows a synthetic intermediate (imidate) to Rhaα1-
2 is a flowchart showing a route for synthesizing 2Glc-azidosphingosine.

FIG. 4 shows a synthetic intermediate (imidate) to Rhaα1-
It is a flowchart which shows the pathway which synthesize | combines 2Glc-cholesterol.

FIG. 5 shows a synthetic intermediate (imidate) to Rhaα1-
It is a flowchart which shows the path | route which synthesize | combines 2Glc-Cer.

FIG. 6 shows a synthetic intermediate (imidate) to Rhaα1-
It is a flow chart which shows the pathway which synthesizes 2Glc-ursolic acid.

FIG. 7: Sugar Rhaα1-2Gal in which galactose is glycosidic-linked to the 4-position of glucose of neohesperidose.
It is a flowchart which shows the synthetic | combination route of (beta) 1-4Glc or this glycoside, a derivative.

FIG. 8: Sugar Rhaα1-2Gal in which galactose is glycoside-linked to the 4-position of glucose in neohesperidose.
It is a flowchart which shows the synthetic | combination route of the sugar which the acetylneuraminic acid couple | bonded with 6-position of the galactose of (beta) 1-4Glc.

FIG. 9: Rhaα1-2Glc-Oct (FIG. 2) and R
Rha of haα1-2Glc-Cer (FIG. 5) is Fuc
It is a flow chart which shows the synthetic route of the sugar converted into.

FIG. 10: Rhaα1-4Glcβ1-Pro, Rha
α1-6Glcβ1-Pro, Rhaα1-4Rhaα
1-6Glcβ1-Pro and Rhaα1-6Glcβ
It is a flow chart which shows a synthetic route of 1-All.

FIG. 11 is a flowchart showing the synthetic pathway of Glcβ1-naringenin.

FIG. 12 is a flowchart showing the synthetic pathway of Glc2Acβ1-naringenin.

FIG. 13: Rhaα1-3Glcβ1-All and Rh
It is a flowchart which shows the synthetic route of a (alpha) 1-3Rha (alpha) 1-2Glc (beta) 1-All.

 ─────────────────────────────────────────────────── ─── Continued Front Page (72) Inventor Takayuki Ishii 6-28-1, Shinjuku, Shinjuku-ku, Tokyo Nisshin Shokuhin Building Mect Co., Ltd.

Claims (3)

[Claims] 1. A glucose derivative represented by the following formula. [Chemical 1] 2. A synthetic intermediate represented by the following formula: 3. Neohesperidose (Rhaα1 → 2Gl
Anti-inflammatory agents, including c).