JPS6094989A - Novel trisaccharide compound and its preparation - Google Patents

Abstract

NEW MATERIAL:O-6-O-Acetyl-2-azido-3, 4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl-( 1 4 )-O-methyl 2,3-di-O-benzyl-beta-D-glycopyranosyluronato-( 1 4 )-O-1,3,6-tri- O-acetyl-2-azido-2-deoxy-D-glycopyranose shown by the formula I (Ac is acetyl; Bn is benzyl; Me is methyl). USE:An intermediate for synthesizing an antithrombotic agent having low side effect. Conversible into a fragment compound of antithrombine bond site of heparin. PREPARATION:A compound shown by the formula II is benzylidenated, treated with dichlorotetraisopropyldisiloxane, acetylated to give a compound shown by the formula III (TIPDS is shown by the formula IV), then benzylated, de-silylated, epoxidized, subjected to azide formation, acetylated, etc. successively to give a compound shown by thr formula V, which is subjected to acetolysis.

Description

[Detailed Description of the Invention] The novel trisaccharide compound of the present invention c)
Heno and phosphorus antithrombin (Antithrom-
bln) can be a fragment compound of the binding site.

Antithrombin (2) is a glycoprotein consisting of a single-chain polypeptide, and is considered to be an important factor as a blood coagulation inhibitor.

On the other hand, heno and phosphorus are mucopolysaccharides that bind to antethrompin and dramatically enhance the anti-coagulation effect of antithrombin. It is thought that wI is composed of the following sugar residues (L. Thunberg,
G. BickstrBrr+ and LJ. Lln
daht.

Carbohydr. Res. / 0θ( 19g.Z
) 393 and references cited therein].

Also of interest to Non-Hatake is that animal experiments have recently shown that small pieces of heparic acid containing the above-mentioned binding site still have antithrombotic activity.

This result indicates that it will be possible to develop effective antithrombotic agents with fewer side effects in the near future.

However, there are no examples of compounds having such a skeleton obtained by chemical synthesis.

Therefore, the present inventors carried out a synthetic chemical investigation of the antithrombin binding site of henoferin, and in the process succeeded in synthesizing the trisaccharide compound of the present invention for the first time.
This completes the present invention.

In other words, before! When trying to synthesize ej[(A),
1) Assuming that the hydroxyl group to be sulfated can be converted from an acetyl group or benzoyl group, and if) the amino group to be oxidized can be converted from an azide group, the following J[(B)
is assumed to be a synthetic precursor.

In the present invention, the trisaccharide moiety (the part surrounded by the dotted line) of the above S sugar [B] was synthesized. ,Me
indicates a methyl group. This is a trisaccharide compound represented by the following formula and a method for producing the same.

The above trisaccharide compound haze is, for example, formula (1):% formula% After benzylidene the compound represented by /.

3-dichloro-/, /, 3*3-ftritube-n-biru-
/, 3-disiloxane (TIPDSC22) and then acetylated to form formula (3): C, TIPt)S
obtains a compound represented by formula (4), deacetylates the compound to obtain a compound represented by formula (4), and benzylates the compound to form formula (
5): Compound shown by ? ! 7tl-obtained, the compound was desilylated to obtain a compound represented by the formula (6): % formula %, the compound was epoxidized to obtain a compound represented by the formula (7); Taking the compound shown below, debenzylidening the compound,
After obtaining a compound represented by formula (9) % formula % and tritylating the compound,
Monochloroacetylation is performed to obtain a compound represented by the formula aQ= (in the formula, Tr represents a trityl group), the compound is detritylated, Jones oxidized, and then methyl esterified to obtain the formula Qll: OBn N .

(In the formula, Me represents a methyl group.) A compound represented by: OBn NH of formula a was obtained by demonochloroacetylating the compound, and the final I□hi compound was -23 (wherein, Bnl represents a pencil group) to form a42Na0BnN.

It can be obtained by obtaining a compound represented by and subjecting the compound to acetolysis.

The compound of the present invention can be a fragment compound of the antithrombin binding site of heno4rin, and can also be a useful intermediate in the synthesis of an effective antithrombotic agent with few side effects. .

The present invention will be explained in more detail below.

The starting material of the present invention, 6-anhydro-β-cellobiose (1), can be obtained by the following method (1.Fujlmakl et al.
Carbohydr, Res, / 0 / (/
9g2)/IIza~/S/].

In addition, one of the starting materials, bromide P (11'd, %
For example, it can be obtained from O-glucose by the following steps (H, Paulsen et al, C
hem, ber,.

197g, //ha2.33'l-, 2,7da7].

The starting material thus obtained (1ν, (from 13,
For example, the target compound of the present invention is obtained by the following steps.

Compound 111 is benzylidened to obtain the benzylidene compound (21).
.

The reaction is carried out in the presence of an acid catalyst such as p-TsQH or MsOH.

DMF is used as the solvent, and the reaction temperature and reaction time are preferably 6θ to qθ°C and /-5 hours, respectively.

The obtained penzolidene body was silylated to form 3
Obtain a cyrillic body whose position is preserved, and use it as a lever! , the 7-position is acetylated to obtain the silyl compound (31).
Dichloro-i, i, 3. ．． 3-tetraisopropyl-7
, 3-i) Using siloxane. Suitable solvents are pyridine and dimethylformamide.

The reaction temperature and reaction time are -ko θ0 to λ5'C, respectively.
1/θ hour to 2 days is appropriate.

Acetylation may be carried out using a conventional method, for example, using an acetic anhydride-pyridine system.

The acetylation step is the fc step that efficiently separates compound (31).

The obtained acetylated 9-silyl form (3) is deacetylated to obtain the J', j'-OH form (41?i-). It is preferable to conduct the reaction in a mixed solvent such as methanol, dioxane, etc. or a mixed solvent thereof.

Reaction temperature and reaction time are each 0-2! ;'C.

70 hours to 2 days is reasonable.

The obtained co',3'-OH form (4) was pendylated to give 1
．． 2',,J1'-0-pencil body (5) is obtained. In this step, the reaction is carried out using benzyl bromide and benzyl chloride in the presence of an alkali hydride such as NaH. In this case, the reaction proceeds efficiently only when n-Bu4Nl is added. Suitable solvents include tetrahydrofuran, dimethylformamide, dimethoxyethane, and the like. The reaction temperature and reaction time are O-2, respectively.
, tc, 6 to IO time is appropriate.

The obtained 2',,J'-0-benzyl compound (5) is desilated to obtain -2*J-OH compound +61't-. In this step, the reaction is carried out using n-B u , NF or diF in a solvent such as tetrahydrofuran, dioxane or dimethoxyethane. The reaction temperature and reaction time were 0-. 2. t"c, time A to 2 days is appropriate.

The obtained 2,3-OH form (6) is epoxidized to obtain an epoxy form (7). This step involves the use of an alkali metal alcoholide, e.g. NaOc, in the presence of tosyl imimezole.
When H,, NaOC2H5, is treated with OCH, KOC2H5, etc., it can be led to an epoxy body at once.

Suitable solvents include chloroform-n-hexane, chloroform-pentane, and chloroform-petroleum ether. Reaction temperature and reaction time are room temperature to solvent boiling point, respectively! ;-10 hours is appropriate.

Furthermore, it is possible to lead to a jepoxy compound by cytosylating or mesylating with tosyl chloride/pyridine or mesyl chloride/pyridine, followed by treatment with an alkali metal alkoxide.

The obtained epoxy body (7) is selectively azidated at the C position, and then acetylated to obtain an azide body (8) in which the 3 position is retained. As the azidating agent, it is preferable to carry out the reaction using sodium azide, potassium azide, lithium azide, etc. in the presence of ammonium chloride. The most suitable solvent is a mixed solvent of dimethylformamide and water. The appropriate reaction temperature and reaction time are 30 to 700°C and 70 hours to 3 days, respectively.

Acetylation may be carried out by a method such as an acetic anhydride-pyridine system.

The obtained azide compound (8) is debenzylidened to obtain a compound (9). This step is performed using, for example, p-TsOH.

This is carried out using CuC4., 2H20, and acetic acid as solvents.

As the solvent, water, THF, EtOH, dioxane, or a mixed solvent thereof is suitable. The appropriate reaction temperature and reaction time are room temperature to gθ°C and hours to 7 days, respectively.

The obtained compound (91) was converted to trityl (T') and then to monochloroacetyl (Iv'1CA) to give trityl.
Nitritylation to obtain the monochloroacetyl compound 11G@ is carried out, for example, by reacting trityl chloride in a pyridine solvent. The appropriate reaction temperature and reaction time are room temperature to /θ0°C and 7 hours to 1 day, respectively.

MCA formation is carried out by adding α-chloro-acetic anhydride to the trityl anhydride without isolating the trityl bar following the above tritylation reaction. The reaction temperature and reaction time are appropriately θ°C to room temperature and 7 to 3 hours, respectively.

After detritylation of the obtained compound αQt, Jones oxidation is performed to obtain a caldenic acid form, and methyl esterification is performed with (2) to obtain MCA, a methyl ester form Qυ. Detritylation is carried out using sulfuric acid, tosylic acid, inorganic salts (CuCl2.2H
20) The reaction is carried out by adding 111 t of peracid, for example, perchlorine. The appropriate reaction temperature and reaction time are OC to room temperature and 30 seconds to per minute, respectively.

A Jones reagent is added to the obtained compound to carry out a reaction. Solvent: acetone, methyl ethyl ketone, CH2Cl
2 is appropriate, and the reaction temperature and reaction time are, respectively,
θ°C to room temperature and 6 to lθ hours are suitable.

Methyl esterification may be carried out by Tsutomi's diazomethane method. For example, the reaction may be carried out by adding diazomethane in a dichloromethane-ether solvent. The reaction temperature and reaction time are preferably 0 to 5C1S to 30 minutes, respectively.

The MCA group of the obtained nine MCA methyl ester aυ is selectively removed to obtain a compound a. This reaction is
In the presence of a base, such as hydrazine, triethylamine, thiourea, etc., ether, methanol, ethanol,
It is carried out in a solvent such as tetrahydrofuran or a mixed solvent thereof. Reaction temperature, reaction time, room temperature to gOC, respectively.
3 hours to 1 hour per day. Obtained c −<<' −
A glycosidation reaction between the OH form +13 and the above pseudomide form is performed to obtain compound Q4t-.

Glycosidation catalysts include HgBr2, Ag,
Go,, AgC1D4, (CH,)gcO3o2CFs
, CF, SOJIAg, etc. can be used. Suitable f# medium is CH2Cl, C4CH2CH2Ct, p1 reaction degree and reaction time are OC-room temperature XQ, respectively.
% - No 2 daily allowance.

The obtained compound (141) was acetolyzed to give the desired 3
Compound 1118 (L!9 is obtained. This reaction is treated with trifluoroacetic acid and acetic anhydride, and the reaction temperature and reaction time are suitably θ°C to room temperature and 6 to /θ hours, respectively.

An example of the process for producing the target compound of the present invention is as follows.

The present invention will be explained in detail below with reference to Examples.

Example/ /,4-anhydro-2,3-0-(tetraisoprobyl disiloxane/,3-diyl)-4! −〇−(ko,
3-di-O-acetyluda, A-0-hensi IJden-β-D-darcobylanosyrun-β-〇-glucobylanose (3) Compound (11 (6,7f, 20.7 mmol), dimethoxy toluene (3,77?, 2'1.g mmol) and p-toluenesulfonic acid monohydrate (2θ)
dimethylformamide</! ;0rd) Place the solution mixture in a 300mm round bottom flask and transfer it to a rotary
Connect it to the evaporator, make it vacuum and take a hot water bath 7! ;Ng
It was treated at 0° C. for 7 hours.

After distilling off the solvent, /, 3-2chloro-/, /, 3°3-detraisoglobin-/, 3-disiloxane (9, 2.
37.5 mmol) in the residual syrup pyridine (/,
li'θml) to the cold solution and the mixture was stirred at room temperature for 7
0:114) Stirred. Anhydrous vinegar # (2011J)'t-
After addition at θ~jC and stirring at room temperature for 6 hours, the mixture was poured into ice water and then extracted with ethyl acetate.

The extract was washed with cold dilute sulfuric acid, once with an aqueous solution, and with water, dried over magnesium sulfate, and concentrated under reduced pressure.

The residue was subjected to silica chromadog 2 (bath: toluene: ethyl acetate = 2!; : / (V/V)), and
■■■■ Compound +31 A, 72 f (yield 61
I%] was obtained.

[11yl embeddedness negative of compound (3)] Specific optical rotation, [α) D −gl, Z0 (C=θ, 7/, C
HCl, )NMRδ: 0. gl;-/, 2! j;
'<m%/2H) (Q(70Mt-tz, eL3ct5
), 2.0. ! r(s, 3H, -oAc), 09
(s, 3H, -0Ac)3,'1g-3.71. <
m, gH)9, &/ (d, /H,J=11.g9
H1, H-3) Il, Ag (d, /HSJ=7.&
/Hz%H-/'n! ;, 29 (s, /H,H-/
)! , 2.3 (t, /H, J=7.2za H2, H-3'
) 3.3/ (S, /H, benzylic proton) elemental analysis: reduction η4 value (C55H540111S'2) '
CS, tig9; H, 7, 37 Actual value C, 3b, g! r:H, 7,33rn-P, 2
20-, i! , 2/°C (acicular crystals) Example co/, 6-anhydroco, 3-0-(tetraisoglobildisiloxane-7,3-diyl)-ri10-(Q, 6
-0-Benzylidene-β-D-glucopyranosyl)-β
-D-Glucobylanose (4) Compound (3) (3,!;
f, da, 711 mmol), hydrazine monohydride di) (/, '12Y,; Ig, '1 mmol) in tetrahydrofuran (30 ml) and methanol <10
The mixture of 11) was stirred at room temperature for 10 hours, and then evaporated under reduced pressure. The residual silon f was dissolved in chloroform and hA
The mixture was washed with water, dried over magnesium sulfate, and then concentrated under reduced pressure. The residual liquid was subjected to silica gel chromatography (bath fJ&:
Chloroform: methanol =, 20: / v/v
) and compound (4) 2 , ? 2t (yield 9q%) was obtained.

[Physical properties of compound (4)] m, p, : gg-g7c (acicular crystal) Specific rotation: [α element'-1Ii7° (C=0, A7
, C) ICt, )lR Nijini B'3'lbOcm' nax Elemental analysis: Calculated value (C,, Hs, 0..5L2) :C
,31,,g! ;:H, 7, 7θ Actual value C,! ;6. g91.7.9/Example 3 /, /, -anhydro-2,3-0-(tetraisoglobildicyxane-/,3-diyl)-4-0-(2,
3-G0-penzylug, 6-0-benzylidene-β
-O-glucopyranosyl)-β-D-glucobylanose (5) hydrogenated) S mmol), tetra-n-butylammonium iodide (8
,7W%,23. l, mmol) and benzyl bromide (g
, /f, was added in small portions at room temperature to a mixed solution of 117.7 mmol of tetrahydrofuran solution, and 3
．． ! ; Stirred for an hour.

Excess lint was destroyed by adding methanol, and the mixture was poured into ice water and extracted with ether. The extract was washed with water and saline and washed with magnesium sulfate. After that, depressurize 11
It shrunk by 1's. The residue was subjected to silica gel chromatography (
Solvent: Toluene: Ethyl acetate-20:/v/v)
A silolag-like compound +51.7.03V (yield: g2%) was obtained.

[Physical properties of compound (5)] Specific rotation: [α]6'-ss, l. (C=0.3/,
, CHCt, ) elemental analysis two ηlyf, value (C45H4
201+"2) 'c, 4da, 7/: H17, Hiroza actual measurement C, A4t, 5'7; H, 7,, 2A example da/, 6-anhydro-'l-0-(2, 3-di0-penjiruk, 6-o-benzylidene-β-〇-glucopyranosyl)-β-D-glucobylanose (6) (n-Bu)4N■, -o (r 7M solution of trahydrofuran/ Ome ) k was added to a cold tetrahydrofuran (30%) solution of compound (5) at θ ~ IC, and then distilled off under reduced pressure. The resulting syrup was dissolved in chloroform, washed with water, and then with magnesium sulfate. , and concentrated under reduced pressure.The residue was subjected to silica gel chromatography <ga
:chloroform:methanol=10θ:/v/v)
3. The compound tel in a shapeless powder is subjected to /q? (
A yield of 9 g) was obtained.

[Physical properties of compound (6)] Specific rotation: [α] δ2-5. θ0(C=θ, S9, CH
Ct, ) elemental analysis two-calculated value (055th 84010 *
%)-+2ot:C, 6! ;,gg;H,ls,2
θ Measured value C, A, S-,, tA; H, 3,9 Example S ko, 3:/, /, -dianhydro-1I-0-(ko.

3-di-0-benzyl-hiro, 6-0-benzylidene-β
-D-glucopyranosyl)-β-〇-glucobyranose (7) Compound +61 (11,5F, 7.4 mmol), tosylimidazole <3. gf, /6.7 mmol), sodium methylate (/, /f, 20.q mmol) in chloroform (lsOrnl, alcohol free), and hexano<1,0 trtl) were refluxed for 15.3 hours. The resulting mixture was cooled, diluted with chloroform, washed with water, dried over magnesium sulfate, and concentrated under reduced pressure. Remaining y
i by silica dal chromatography (elution: toluene:
The compound (
71J, g f (discharge of raw material (6) #Jtj#
, yield based on ? /%) vl-obtained. In addition, the raw material (
6) was recovered /, J, jt.

[Physical properties of compound (7)] m, p,: 1g3. θ-/za15' (acicular crystal) NMR
δH: ,3.3g (to/H,H-,?)(lIoo
MHz, CDCJ, ) 3. <43(ddd, /H
, J=11. /! ; and 4(, g91-1z, H-!
;' )3, da9 (dd, /H, J=ko, 93 and 3
．． 17Hz, H-λ) 3,! ;'l (dd, /H, J=9.3θ and 7.
57)-1z.

H-co') 3d, g-3, g2 (m%, S-H, H-Aa, 4b
, 3', t' and 6'8) 3, Wako (s, /H, H-riQ, 3j (dd, /H, J=!;, /3 and 10.5
OHz, H-A'b) Q, &5 (m, /H,H-,5-)Il,b7 (
d, /H, J=7.37Hz, H-/') &, g
Ko Hiroshi, 9 (m, da H, benzilguru = f) 3,! ;
g (s, Il-1, benzylidene proton)! ;,
'M (d, /H, J=3./gHz, H-/) element cumulative analysis: calculated value CC5b"5aOt)'C,4g,9g',
H,! ;,96 Real oil J1ifi: 0% 6g,,? ,5-;H
,3,9u Example 6 3-0-acetyl-/,6-anhydrocoazidocodeoxy-Hiro-〇-(2,3-)-〇-benzyru &, , A-0-pensoliden-β-D- glucopyranosyl)-β-D-glucobylanose (8) Compound +71 (/,, 2F, co, / mmol), ammonium chloride (/, 3t, 2 g mmol), sodium azide (deθθq, /l? , g mmol] in dimethylformamide (26 tst) and water (11 ml)
Heated at tD mixed qmt-1100C for 17 hours. The resulting reaction mixture was cooled, poured into ice water, and then extracted with chloroform. The extract was washed with water, dried over low acid magnesium, and condensed under reduced pressure. O-,
Acetic anhydride (2,1) was added at tC and then stirred at room temperature for 3 hours. The mixture was removed under reduced pressure and the residue was subjected to silica gel column coomadography (*m:m:toluene:ethyl:=coθ:/v/v) to obtain compound (81).
g g IIη (yield: 6 h) was obtained.

[Physical properties of compound (6)] Specific rotation: [α) p2-9, / 00 (C=0,
Ilhiro, CHC, t, ) NMRaH: (900 MHz, CDC4) 2, // (s, 3H, -0Ac) 3.22 (S, /H, H-, 2), 3. lI/-3,'lza(rnX/H,H-5')
4! , A? (d, /H,J=7.!7H1,H-/
')S, -g (Ha/H,H-3)! ;, lI9 (s, /H,H-/)S, 3g (s
, /H, benzylidene proton) element cumulative analysis two calculated values (C
AsH57Nl101゜)C,43,72:ni-5-,
A,! t; Haya 6.37 Actual value 63. The S;ni! ;,
63:tt! ;, 73 Example 7 3-0-acetyl-/, 6-anhydrocoacito-
2-deoxider〇-(2,?-di〇-benzyl-β-〇-glucopyranosyl)-β-D-glucobylanose (9) Compound (e) (77,?llv, /,/7 mmol)
A mixture of a tetrahydrofuran (10111) solution of chloride, 2#, uH20(/,g,g,a) and ethanol (/6*f) was refluxed for 7 hours.The resulting reaction product was cooled, After neutralization by adding aqueous sodium bicarbonate, it was filtered. The P solution was extracted with chloroform, and the extract was dried over magnesium sulfate and concentrated under reduced pressure. Physical properties] Specific rotation: [α)'; +, 2.2.A° (C = 0.75
i', CHC/3)IR: ν1IlaX 3j 00
cm ' Elemental analysis two calculated values (C2B'33N3010
)c, sr, #, H%s, 1.2. N, 7
．． 3s"jl". ,3F,7j,H,t,I□18.6
．． 66 Example 3-0-acetyl-/,6-anhydrocoazidocodeoxy-1I-0-(co,3-di〇-benzyl-1I-0-(α-chloroacetyl)-6-0- ) I
J-thyl-β-〇-glucopyranosyl]-β-D-gelcopidinose compound (9) (67,2, 7.2 mmol) and trityl chloride ('/-92, /0 g mmol) in pyridine ( The mixture of 2θ punishment) solution was heated in gSC for q hours. To this was added α-chloroacetic anhydride (glO cape, cog mmol) in portions at 0-5 °C, stirred for 30 min at room temperature, and then poured into ice water. , and ethyl acetate.The extract was washed with cold dilute sulfuric acid, 1 ml of hydrogen chloride solution, and water, dried with magnesium sulfate, and concentrated under reduced pressure.The residue was subjected to silica gel column chromatography (solvent: hexane-ethyl acetate = 3
2/v/v) and compound al 9 g/vu
y (yield: 79 h) was obtained.

[Physical properties at the beginning of compounding]

NMRaH: / , 911(s, , ?H, -0Ac
) Example De 3-0-acetyl-/,6-anhydro-a-azido-
copoxy-p-o-(methylco,3-)-〇-benzylugoo-(α-chloroacetyl)-β-O-glucopyranosyl uronate]-β-D-glucobylanose aυ compound + IG (369 A (796 solution) of chloroform (6
After stirring the solution mixture to room temperature for 7 minutes, it was diluted with chloroform.

The organic layer was washed with t-is water, dried over magnesium sulfate, and concentrated under reduced pressure. Cold acetate of residual Sillag 7 (/30
ae) Add Jones reagent (/θm) to the solution at o-,re
1) was added briefly, and the mixture was further stirred at room temperature for 30 minutes. Methanol was added to destroy excess reagent and the mixture was evaporated in vacuo. Then, the residue was suspended in ethyl acetate-water, and the aqueous layer was extracted with ethyl acetate. The extract was washed with aqueous sodium bicarbonate and water, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (solvent: chloroform:
Methanol (q:/v/v) was applied to obtain uronic acid.

This was esterified with diazomethane in dichloromethane-ether to give powdery compound (11) 2 / @
W9 (yield 33%) was obtained.

[Physical properties of compound aυ]

NMRJH: (lIooMHz, CDC1,) Ko, /θ (S,,,?H,-0AC)3.23 (s
, /H,H-CO) 3.1s-3,gtiCm%AH) 3,72 (s, 3H,-COOMe)3.9!
;(d, /H,%J=10.θ/H2,H-,t'
)'I −0/ (ds/K J =7−!r
7 Hzs HA, ) 9,, S-za (ds /Hs
J=j-37Hz, H! ;)”i, bg (d, /H,
J=7. j7HzXH-/')! ;, /7 (dd, /
H%J=7.7rito10. θHz, H-11')! ,2
7 (m%/H, H-,?)! ;、! ? 0 (S,/)-1,H-/) Elemental analysis: Calculated value (C,,H,4C/Jchi0,2)CS! ;3.07
;H,j,07;N,6.22;Ct,5
,．． 24 actual value C,,';11.79:H,3,01f
:N, 3.7'Z:C1,! ;, b3 Example/θ 3-0-7 cetyl/, 4-anhydrocoazidocodeoxy-Hiro-〇-(methylco, 3-di-0-benzyl-β-D-glucobylanosyl uronate)- β-D
-Gelcopi 2-north ali compound Oυ (20gW, θ, 3
/ mmol) and Thio'Z L'7 (27”F, 0-3
A mixture of a solution of J mmol) in ethanol C15wt1) was refluxed for 6 hours, and after cooling, the solvent was evaporated under reduced pressure to half the volume, which was diluted with dichloromethane. The organic layer was washed with water, dried over magnesium sulfate, and concentrated under reduced pressure. The IA residue was subjected to silica thin layer chromatography (MiFl agent: ethyl acetate/V/V) to obtain an amorphous powder of compound 62/3/Misaki (yield/%). Ta.

[Physical properties of compound α4] Specific rotation: [α 5 + gθ° (C = 0.0!;, CH
C4,) IR: ν 3'160cm-' ax Elemental analysis: Calculated value (C!?'gAN5011) 'C%
, S'za, θ7; H1 left, 55; N, 7.0/actual value C
,,! -7. '76;H,,t,,S-4;N,A,,
25 Examples/1 0-4-0-acetyl-coazido 3.11-cy〇-benzyl-1-deoxy-α-logelcopi-2-nosyl-(/→hiro)-0-methyl co,3-di0 -Benzyl-β-O-glucobyranosyl uronate-(/→Q)
-0-3-0-aceteru/,6-anhydrocoasodocodeoxy-β-D-glucobylanose I Socroomer of compound al(,20,!t,o,a glymol) 7 ( , tvte) dissolved 'e, k, compound Q3 (/3/vv, 0.22 mmol), powdered molecular sheepsge A (/,, 2F) and mercury bromide (
73 mmol) under an argon atmosphere, and the mixture was stirred at room temperature for 3 days.

The obtained reaction product was filtered, and the P solution was washed with an aqueous silver nitrate solution, an aqueous sodium bicarbonate solution, and water, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was prepared by silica thin layer chromatography (
An amorphous powder of Compound tJ49/Misaki (yield 69% based on the consumption amount of Compound GJ) was obtained. In addition, 5/η of the raw material storage 0 was collected once.

[Physical properties of compound I] Ratio light #: [α]D +λg, o° (C=0.66, C
HC4,)NMRδH: ko, θJ(ssJH, -0Ac) J, 10(s, t7
H, -0Ac)3, co/(S, /H,H-,2)3,. 2A (dd, /H, J=, 7.60 and /θ, 5
OHz, H-ko")J,,t/(t, /H,J=i7
9Hz, H-II")J, Au(d%/1-kH-I
I) 3.7&(s, JH, -CO2Me), 3. gg
(dd, /H, J=g, 7W and 10.2AHzXH-
3")t7.?A(d, /H,J=nib-;-2Hz
s HJ') da, 01(d, /H, J=A, za'I
Hz %H-A ) 11, /! (t, /H,J=za,79Hz%H-p/)9.47(d% /H,J=
7.37Hz, Hi') So, 2u (m, /H,H-
J), L4'? (s%/H%H-/)! ;、! ;3
(d, /H%J=3, '?OHz%H-/")
Elemental analysis: Calculated value C5, H56N60, 6:c, lsO
,t/',H,! ;、! r9; N, g, 33 actual measurement value C
, 60,93'', H% 3.6;
Benzyl-copeoxy-α-0-glucopyranosyl-
(/-+da)-o-methylco, 3-di-O-benzyl-
β-D-glucobyranosyl uronate-(/-1)-0
-/, 3. A-) So0-acetyl-coadiP-copeoxy-〇-glucobylanose a9 Compound +14 (4' ? "9 sθ, oti-'y
A mixture of acetic anhydride (jm) solution of trifluoroacetic acid (0.3 ytl) and trifluoroacetic acid (0.3 ytl) was stirred at room temperature for 70 hours.

After distilling off the reactants under reduced pressure, the residue was subjected to preparative silica thin layer chromatography (developing agent: benzene-ethyl acetate = 4t:
/ v/v ), compound 119 as an amorphous powder,
? / #I9 (yield 6θ) was obtained.

[Physical properties of compound a9] Specific rotation: [α) o = + tig, to (c = θ, i, c
+cj, ) NMRaH: ko, θ%? (S,,71-1.-0Ac),2.07
(s, 3H, -0Ac)2.10(s, 3H, -0Ac
), 2. ．． 2θ(s, 3H, -0Ac)3, 71
．． (s, JH, -COOCH,)A, #2.2(d,
/H, J=3.661-1x%H-/) Elemental analysis: Calculated value (C55'42N6018・H2O): C, &f
fJ/: H, j, 7/: N, ri, Dada actual measurement value 0% 3g
, Dada;H%! ;,AI”,N,l,,99 Patent applicant RIKEN

Claims (1)

[Claims] (1) Formula: %Formula% (In the formula, Ac is an acetyl group, Bn is a benzyl group, Me
indicates a methyl group. ) A trisaccharide compound represented by 121 Formula: After benzylidening the compound represented by, 7.3-dichloro-/, /, 3.3-tetraisop-tetrapyru/,
After treatment with 3-disiloxane (TIPDSC/,),
acetylation to obtain a compound of the formula: (wherein TIPDS is); deacetylation of the compound to obtain a compound of 1PLIb; , the compound is desilylated to obtain a compound represented by the formula: % formula %, the compound is engineered to obtain a compound represented by the formula: , the compound is azidated, and then acetylated to form the formula A compound represented by the formula % is obtained, the compound is debenzylidened to obtain a compound represented by the formula: After total tritylation of the compound,
After monochloroacetylation, a compound represented by the formula: (wherein T represents a trityl group) was detritylated, followed by Jones oxidation, and then methyl esterification to obtain the formula: (wherein, Me represents a methyl group) and demonochloroacetylated the compound to obtain a compound represented by the formula:
represents a benzyl group. ) to obtain a compound represented by the formula: and gold acetolysis of the compound,
A novel method for producing a trisaccharide compound, characterized by obtaining a compound represented by the formula: % Formula %.