JP2762859B2 - Cyclodextrin derivative and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel cyclodextrin derivative and a method for producing the same.

[0002]

2. Description of the Related Art Cyclodextrin is a compound having a hydrophobic cavity in the molecule and a hydrophilic outer surface and having a function similar to an oil-in-water micelle. Such a cyclodextrin takes in a hydrophobic guest molecule according to its cavity diameter to form a complex in an aqueous solution, and a solid clathrate can be isolated depending on the preparation method. Since the physicochemical properties of the guest molecule can be subtly changed by this stereoselective interaction, it can be expected to be effectively used for pharmaceuticals, and it is widely used in various fields and is being used. Compound.

[0003] In particular, in the case of a cyclodextrin derivative partially leaving a hydroxyl group at the 2-, 3- or 6-position of cyclodextrin, the inclusion ability is greatly changed by the interaction with the hydroxyl group. It can be expected that the physical properties and the like can be greatly changed.

For example, dimethylcyclodextrin in which the hydroxyl groups at the 3- and 6-positions disclosed in Japanese Patent Application Laid-Open No. 3-137103 is easily dissolved in oil, exhibits surface activity, and has a reduced hygroscopic property. Has the advantage of greatly expanding its use in pharmaceuticals.

For the synthesis of intermediates used for such cyclodextrin derivatives, see J. Carbohydr.
em., 7 293-308 (1988); Carbohydr. Res., 187 203-22
1 (1989); Carbohydr. Res., 192 366-369 (1989).

[0006]

However, in the synthesis of such a cyclodextrin derivative partially leaving the hydroxyl group at the 2-, 3- or 6-position, it is necessary to selectively react a specific hydroxyl group in the process. It was very difficult and complicated.

[0007] That is, an object of the present invention is to provide a novel cyclodextrin derivative having an acetyl group introduced at either the 2, 3 or 6 position, or at the 2, 6 or 3, 6 position, and a process for producing the same. It is in.

It is another object of the present invention to provide a method for easily producing the above cyclodextrin derivative.

[0009]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies in view of the above problems, and as a result, the object of the present invention was to provide an acetylcyclo compound represented by the following formula (1), (2) or (3). They have been found to be achieved by providing a dextrin derivative or a diacetylcyclodextrin derivative represented by the following formula (4) or (5).

[0010]

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The object of the present invention is attained by the following method for producing a cyclodextrin derivative.

(1) Hydroxy groups at the 2- and 3-positions of (6-O-tert-butyldimethylsilyl) cyclodextrin are benzylated, allylated or pyranylated, and then desilylated to obtain a cyclodextrin derivative. A method for producing 6-acetyl-cyclodextrin, wherein the protecting group is removed after acetylating the hydroxyl group at the 6-position.

(2) The (6-O-tert-butyldimethylsilyl) cyclodextrin in which the hydroxyl group at the 2-position is benzylated or allylated is desilylated, benzylated, allylated or pyranylated, and then substituted at the 2-position. A method for producing 2-acetyl-cyclodextrin, wherein a benzyl group or an allyl group is eliminated and then acetylated.

(3) A process for producing 3-acetyl-cyclodextrin, wherein the hydroxyl group at the 3-position of (2,6-di-O-tert-butyldimethylsilyl) cyclodextrin is acetylated and then desilylated.

(4) After acetylation of the 3-position hydroxyl group of (6-O-tert-butyldimethylsilyl) cyclodextrin in which the 2-position hydroxyl group is benzylated or allylated,
A method for producing 3-acetyl-cyclodextrin, wherein the benzyl or allyl group at the 2-position is eliminated and then desilylated.

(5) A method for producing 6-acetyl-cyclodextrin by reacting N-acetylimidazole with cyclodextrin.

(6) A method for producing 6-acetyl-cyclodextrin by reacting acetyl chloride with cyclodextrin.

(7) After desilylation of (6-O-t-butyldimethylsilyl) cyclodextrin in which the hydroxyl group at the 2-position is benzylated or allylated, acetylation is carried out.
A method for producing 3,6-diacetylcyclodextrin.

(8) Hydroxy group at position 2 is benzylated or allylated (3-O-t-butyldimethylsilyl) cyclodextrin The benzylation, allylation or pyranylation of the hydroxyl group at position 3 is followed by desilylation. And then 2
A method for producing 2,6-diacetylcyclodextrin, which comprises removing a benzyl group or an allyl group at the 2-position and then acetylating.

(9) The hydroxyl group at the 3-position of (2,6-di-O-tert-butyldimethylsilyl) cyclodextrin is subjected to benzylation, allylation or pyranylation, followed by desilylation, followed by acetylation. For producing 2,6-diacetylcyclodextrin.

Hereinafter, the present invention will be described more specifically.

In the present invention, cyclodextrin is n
Those with 6 are called α-cyclodextrin, those with n 7 are called β-cyclodextrin, and those with n 8 are called γ-cyclodextrin.

The following are specific examples of the reaction of the monoacetylcyclodextrin of the present invention. However, in some cases, cyclodextrin is abbreviated as CD hereinafter.

[0024]

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[0025]

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The above reaction examples (1) and (2) are specifically carried out by the following reactions. Reaction [1] β-CD (n = 7) is dissolved in dehydrated pyridine and cooled to 0 to 5 ° C. under a nitrogen atmosphere. Then added dropwise ^t BDMSi · Cl were dissolved in dehydrated pyridine, After completion of the dropwise addition 0 to 5 ° C.
For 1 hour and at room temperature for 12 hours. After completion of the reaction, reprecipitation is performed from a large amount of water, and the precipitate is separated by filtration, washed well with water, and dried. Thereafter, purification was performed by silica gel column chromatography, and the obtained [A] was recrystallized three times from ethanol. (Yield: about 80%)

Reaction [2] After dissolving [A] in dehydrated DMF, BaO, Ba (OH) _2.
8H ₂ O is subsequently added. Benzyl bromide is added dropwise to the system at room temperature, and after completion of the addition, sodium iodide is added and the mixture is stirred for 24 hours. Stirring was added After completion of the reaction methanol and then filtered to remove insoluble materials, the filtrate of methylene chloride was added 1M-H ₂ SO
_4. Wash with water in order and dry the organic phase, then concentrate under reduced pressure at 40 ° C or lower. A small amount of ethanol is added to the residue and reprecipitated from a large amount of water. The precipitate was thoroughly dried and purified by silica gel column chromatography, and the obtained [B] was recrystallized from ethanol. (Yield: about 70%)

Reaction [3] [B] is dissolved in dehydrated methylene chloride, and the solution
Cool to 5 ° C. Next, a diethyl ether complex of boron trifluoride is added dropwise to the system, and after completion of the addition, the mixture is reacted at 0 to 5 ° C. for 2 hours and at room temperature for 12 hours. After completion of the reaction, the organic phase was washed with ice-cold water, the organic phase was dried and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography. The obtained [C] was recrystallized from a diethyl ether / methanol system. . (Yield: about 70%)

Reaction [4] [C] is dissolved in THF, and 3,4-dihydro-
Add 2H pyran and stir. Then, at room temperature, 1 to 2 drops of hydrochloric acid are added and reacted for 12 hours. After the reaction is completed, KOH is added to the system.
And stirred for 30 minutes at room temperature. After filtering off KOH, the solution is concentrated under reduced pressure. The residue was separated and purified by alumina column chromatography to obtain [D]. (Yield: about
65%)

Reaction [5] [D] was dissolved in a 2/1 solution of ethanol / acetic acid, and 10%
After adding Pd / C as a catalyst, hydrogenation is performed (40
° C, 5 kg / cm ² ). When the hydrogen pressure stopped decreasing, the reaction was terminated, Pd / C was separated by filtration, the solution was concentrated under reduced pressure, and the residue was separated by alumina column chromatography.
Purification gave [E]. (Yield: about 85%)

The reaction [6] -1 [E] is dissolved in dehydrated pyridine, and acetic anhydride is added dropwise at room temperature. After the completion of the dropwise addition, the reaction is carried out at 60 ° C. for 12 hours. After completion of the reaction, pyridine is concentrated under reduced pressure, a small amount of ethanol is added to the residue, and reprecipitation is performed from a large amount of ice-cold water. The precipitate was separated by filtration, dried well, and separated and purified by alumina column chromatography to obtain [F]. (Yield: about 80%)

Reaction [6] -2 [E] is dissolved in dehydrated pyridine (or triethylamine), and acetyl chloride (or acetyl bromide) dissolved in methyl chloride is added dropwise under a nitrogen atmosphere. 0-5 after dropping
The reaction is performed for 2 hours at room temperature and 6 hours at room temperature. After completion of the reaction, the pyridine was concentrated under reduced pressure, and a small amount of ethanol was added to the residue.
Perform reprecipitation from a large amount of ice-cold water. The precipitate was separated by filtration, dried well, and separated and purified by alumina column chromatography to obtain [F].

Reaction [7] [F] is dissolved in THF, and hydrochloric acid is added thereto.
Let stir for minutes. After completion of the reaction, the reaction mixture is left to cool, KOH is added at room temperature, and the mixture is stirred for 30 minutes. After KOH was filtered off, THF was concentrated under reduced pressure, and the residue was separated and purified by silica gel column chromatography to obtain 2-acetyl β-CD [G].
(Yield: about 55%)

Reaction [8] [A] is dissolved in dehydrated DMF and cooled to 10 ° C. under a nitrogen atmosphere. NaH is added to the system, stirred at that temperature for 2 hours, then benzyl bromide is slowly added dropwise and more sodium iodide is added. 1 hour at 10 ° C, 24 hours at room temperature
Stir for hours. After completion of the reaction, methanol is added, the mixture is stirred for 30 minutes, and filtered. The filtrate was concentrated under reduced pressure at 40 ° C. or lower, and the residue was reprecipitated from a small amount of methanol, and filtered.
The filtrate is dried and separated by silica gel column chromatography. The obtained [H] was recrystallized from ethanol and purified. (Yield: about 60%)

Reaction [9] [I] was obtained in the same manner as in the reaction [3], except that the obtained compound was not recrystallized using [H] instead of [B]. (Yield: about 70%)

The reaction [10] -1 was carried out in the same manner as in the reaction [6] -1 except that [I] was used instead of [E], and silica gel column chromatography was used instead of alumina column chromatography. [J] was obtained. (Yield: about 70%)

Reaction [10] -2 [I] was used in place of [E], and separation and purification were carried out by silica gel column chromatography in place of alumina column chromatography. [J] was obtained.

Reaction [11] [J] was carried out in the same manner as in Reaction [5] except that [J] was used in place of [D], and silica gel column chromatography was used instead of alumina column chromatography.
-Acetyl β-CD [K] was obtained. (Yield: about 80%)

Reaction [12] β-CD (n = 7) is dissolved in dehydrated DMF, and imidazole is added at room temperature. Then under an argon atmosphere ^t BDM
Add Si · Cl and dissolve. The system is heated slowly and allowed to react at 90-100 ° C for 24 hours. After the reaction is completed, allow to cool,
The residue was distilled off under reduced pressure DMF and extracted with methylene chloride / water, the organic phase is 1M-H ₂ SO _4, dried after washed with water, aqueous NaHCO _3. The organic phase was concentrated under reduced pressure, and the residue was recrystallized from a methylene chloride / methanol system and purified to obtain [L]. (Yield: about 65%)

Reaction [13] -1 [L] was used in place of [E], and the reaction conditions were 100 ° C. and 36 hours, except that separation and purification were performed by silica gel column chromatography instead of alumina column chromatography. [M] was obtained in the same manner as in [6] -1. (Yield: about 90%)

Reaction [13] -2 [L] is dissolved in a mixed solvent of dehydrated DMF (or THF) and pyridine (or only triethylamine), and dissolved in DMF or THF at 0 to 5 ° C. under a nitrogen atmosphere (or acetyl chloride (or (Acetyl bromide) is added dropwise. 0-5 after dropping
The reaction is carried out at 2 ° C. for 2 hours and at room temperature for 12 hours. After completion of the reaction, the solvent is concentrated under reduced pressure, a small amount of acetone is added to the residue, and reprecipitation is performed with a large amount of ice-cold water. The precipitate is separated by filtration, dried and then separated and purified by silica gel chromatography [M].
I got (Yield: about 90%)

Reaction [14] 3-Acetyl β-CD [N] was obtained in the same manner as in Reaction [3], except that the obtained compound was not recrystallized by using [M] instead of [B]. Was. (Yield: about 50%)

The reaction [15] -1 was carried out in the same manner as in the reaction [6] -1 except that [B] was used instead of [E], and silica gel column chromatography was used instead of alumina column chromatography. [O] was obtained. (Yield: about 80%)

Reaction [15] -2 [O] was obtained in the same manner as in Reaction [13] -2, except that [B] was used instead of [L].

Reaction [16] Using [O] in place of [D], separation by silica gel column chromatography in place of alumina column chromatography, and the obtained [P] was recrystallized from methanol and purified. [P] was obtained in the same manner as in the reaction [5] except that the reaction was carried out. (Yield: about 65%)

Reaction [17] 3-AcetylCD [N] was obtained in the same manner as in reaction [3] except that [P] was used instead of [B]. (Yield: about 50
%)

In the above reaction [1], when α-CD is used instead of β-CD, α-CD is replaced with dehydrated pyridine / dehydrated DM instead of dissolving β-CD in dehydrated pyridine.
The reaction can be carried out in the same manner as in the reaction [1], except that the compound [A] is dissolved in an F = 4/3 solution, and the obtained [A] is recrystallized from a methylene chloride / ethanol solution instead of recrystallizing with ethanol.

When γ-CD is used instead of β-CD, the same operation as in reaction [1] is performed except that [A] is recrystallized from a methylene chloride / methanol solution instead of recrystallizing with ethanol. Can do it.

Reaction [18] β-CD (n = 7) is dissolved in dehydrated pyridine and stirred at room temperature under a nitrogen atmosphere. In the system, N dissolved in dehydrated pyridine
-Acetylimidazole is added dropwise. After dropping,
Stir at room temperature for 1 hour then at 40-50 ° C for about 30 hours. After completion of the reaction, pyridine is distilled off under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain the desired product [K]. (Yield: about 80%)

Reaction [19] β-CD (n = 7) is dissolved in dehydrated pyridine and stirred at −5 ° C. under a nitrogen atmosphere. Acetyl chloride dissolved in methylene chloride is slowly dropped into the system. After dropping
The reaction is carried out at 5 ° C for 2 hours and at 5 ° C for 6 hours. After completion of the reaction, pyridine and methylene chloride are distilled off at room temperature under reduced pressure, and the residue is extracted with a chloroform / water system. Chloroform layer is 1M
Wash with sulfuric acid, neutralize, dry and concentrate. The residue is separated and purified by silica gel column chromatography to obtain the desired product [K]. (Yield: about 65%)

In the above reactions [18] and [19], β-
When α-CD is used in place of CD, the reaction is carried out except that α-CD is dissolved in a 4/3 solution of dehydrated pyridine / dehydrated DMF instead of dissolving β-CD in dehydrated pyridine [18].
And [19].

Next, specific reaction examples of diacetylcyclodextrin will be shown.

[0053]

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The above reaction example (2) is specifically carried out by the following reaction. Reaction [1] β-CD (n = 7) is dissolved in dehydrated pyridine and cooled to 0 to 5 ° C. under a nitrogen atmosphere. Then added dropwise ^t BDMSi · Cl were dissolved in dehydrated pyridine, After completion of the dropwise addition 0 to 5 ° C.
For 1 hour and at room temperature for 12 hours. After completion of the reaction, reprecipitation is performed from a large amount of water, and the precipitate is separated by filtration, washed well with water, and dried. Thereafter, purification was performed by silica gel column chromatography, and the obtained [A] was recrystallized from ethanol. (Yield: about 80%)

Reaction [2] After dissolving [A] in dehydrated DMF, BaO, Ba (OH) ₂
· 8H ₂ O followed by the addition. Benzyl bromide is added dropwise to the system at room temperature, and after completion of the addition, sodium iodide is added and the mixture is stirred for 24 hours. After the completion of the reaction, methanol is added, the mixture is stirred, and then insolubles are filtered off. Add methylene chloride to the filtrate and add 1M
-H ₂ SO _4, washed sequentially with water, dried and the organic phase is concentrated below under reduced pressure 40 ° C.. A small amount of ethanol is added to the residue and reprecipitated from a large amount of water. The precipitate was thoroughly dried and purified by silica gel column chromatography, and the obtained [B] was recrystallized from ethanol. (yield:
About 70%)

Reaction [3] [B] was dissolved in dehydrated methylene chloride, and the solution
Cool to 5 ° C. Next, a diethyl ether complex of boron trifluoride is added dropwise to the system, and after completion of the addition, the mixture is reacted at 0 to 5 ° C. for 2 hours and at room temperature for 12 hours. After completion of the reaction, the organic phase was washed with ice-cold water, the organic phase was dried and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography. The obtained [C] was recrystallized from a diethyl ether / methanol system. Was. (Yield: about 70%)

The reaction [4] -1 [C] is dissolved in dehydrated pyridine, and acetic anhydride is added dropwise at room temperature. After the completion of the dropwise addition, the reaction is carried out at 60 ° C. for 12 hours. After completion of the reaction, pyridine is concentrated under reduced pressure, a small amount of ethanol is added to the residue, and reprecipitation is performed from a large amount of ice-cold water. The precipitate was separated by filtration, dried well, and then separated and purified by silica gel column chromatography to obtain [D]. (Yield: about 85%)

The reaction [4] -2 [C] is dissolved in dehydrated pyridine, and the solution is dissolved at 0 to 5 ° C. in a nitrogen atmosphere.
Acetyl chloride (or acetyl bromide) dissolved in methyl chloride is added dropwise. After completion of the dropwise addition, the mixture is reacted at 0 to 5 ° C for 2 hours and at room temperature for 6 hours. After completion of the reaction, pyridine is concentrated under reduced pressure, a small amount of ethanol is added to the residue, and reprecipitation is performed from a large amount of ice-cold water. The precipitate is separated by filtration, dried well, and then separated and purified by silica gel column chromatography [D].
I got

Reaction [5] [D] was dissolved in a 2/1 solution of ethanol / acetic acid, and 10%
After adding Pd / C as a catalyst, hydrogenation is performed (40
° C, 5 kg / cm ² ). When the hydrogen pressure stopped decreasing, the reaction was terminated, Pd / C was separated by filtration, the solution was concentrated under reduced pressure, and the residue was separated and purified by silica gel column chromatography to obtain 3,6-diacetyl CD [E]. Was. (Yield: about
80%)

Reaction [6] [B] is dissolved in THF, and 3,4-dihydro-2Hpyran is added dropwise. Add 1-2 drops of hydrochloric acid to the system and at room temperature
Stir for 12 hours. After the reaction is completed, KOH is added to the system,
Stir at room temperature for 30 minutes. After filtering off KOH, the solution is concentrated under reduced pressure. The residue was separated and purified by alumina column chromatography to obtain [F]. (Yield: about 70%)

Reaction [7] [G] was obtained in the same manner as in the reaction [3] except that the obtained compound was not recrystallized by using [F] instead of [B]. (Yield: about 70%)

Reaction [8] [H] was obtained in the same manner as in reaction [5] except that [G] was used instead of [D]. (Yield: about 85%)

[I] was obtained in the same manner as in reaction [4] -1, except that [H] was used instead of reaction [9] -1 [C]. (Yield: about 80%)

Reaction [9] -2 [I] was obtained in the same manner as in reaction [4] -2, except that [H] was used instead of [C].

Reaction [10] [I] is dissolved in THF, hydrochloric acid is added thereto, and the mixture is stirred at 40 ° C. for 30 minutes. After completion of the reaction, the reaction solution is left to cool, and KOH is added at room temperature
Stir for 30 minutes. After KOH was filtered off, THF was concentrated under reduced pressure, and the residue was separated and purified by silica gel column chromatography to obtain [J]. (Yield: about 55%)

Reaction [11] β-CD (n = 7) is dissolved in dehydrated DMF, and imidazole is added at room temperature. Then under an argon atmosphere ^t BDM
Add Si · Cl and dissolve. The system is heated slowly and allowed to react at 90-100 ° C for 24 hours. After the reaction is completed, allow to cool,
The residue was distilled off under reduced pressure DMF and extracted with methylene chloride / water, the organic phase is 1M-H ₂ SO _4, dried after washed with water, aqueous NaHCO _3. The organic phase was concentrated under reduced pressure, and the residue was recrystallized from a methylene chloride / methanol system and purified to obtain [K]. (Yield: about 65%)

Reaction [12] [L] was obtained in the same manner as in reaction [6] except that [K] was used instead of [B]. (Yield: about 70%)

Reaction [13] [L] was used in place of [B], and the reaction was carried out at room temperature for 24 hours instead of 12 hours at room temperature, and further without recrystallization with diethyl ether / methanol system. [M] was obtained in the same manner as in [3]. (Yield: about 60%)

Reaction [14] -1 [N] was obtained in the same manner as in the reaction [4] -1, except that [M] was used instead of [C]. (Yield: about 80%)

Reaction [14] -2 [N] was obtained in the same manner as in reaction [4] -2, except that [M] was used instead of [C].

Reaction [15] 2,6-Diacetyl CD [J] was obtained in the same manner as in Reaction [10], except that [N] was used instead of [I]. (yield:
About 60%)

In the above reaction [1], when α-CD is used instead of β-CD, α-CD is replaced with dehydrated pyridine / dehydrated DM instead of dissolving β-CD in dehydrated pyridine.
The same operation as in the reaction [1] can be performed except that the compound is dissolved in an F = 4/3 solution.

When γ-CD is used instead of β-CD, the same operation as in reaction [1] can be performed.

[0074]

As described above in detail, according to the present invention, a novel cyclodextrin derivative having an acetyl group introduced at either the 2, 3 or 6 position or at the 2, 6 or 3, 6 position is obtained. can get. Further, a cyclodextrin derivative which is easily soluble in oil, exhibits surface activity, and has reduced hygroscopicity can be obtained.

Further, according to the present invention, the desired product can be surely obtained because the chemical modification is aimed at a specific position of the hydroxyl group of cyclodextrin at each reaction step.

Claims (11)

(57) [Claims] 1. An acetylcyclodextrin derivative represented by the following formula (1), (2) or (3). Embedded image 2. A cyclodextrin derivative obtained by subjecting the hydroxyl groups at the 2- and 3-positions of (6-O-tert-butyldimethylsilyl) cyclodextrin to benzylation, allylation or pyranylation and then desilylation. A method for producing 6-acetyl-cyclodextrin, wherein the protecting group is removed after acetylation of the hydroxyl group at position 1. 3. A method for desilylation of (6-O-tert-butyldimethylsilyl) cyclodextrin in which the hydroxyl group at the 2-position is benzylated or allylated, followed by benzylation, allylation or pyranylation, followed by benzylation at the 2-position A method for producing 2-acetyl-cyclodextrin, which comprises removing a group or an allyl group and then performing acetylation. 4. A method for producing 3-acetyl-cyclodextrin, which comprises acetylating the hydroxyl group at the 3-position of (2,6-di-O-tert-butyldimethylsilyl) cyclodextrin and then desilylating the hydroxyl group. 5. After acetylating the 3-position hydroxyl group of (6-O-tert-butyldimethylsilyl) cyclodextrin in which the 2-position hydroxyl group is benzylated or allylated, the benzyl group or allyl group of the 2-position is converted to a benzyl group or an allyl group. A method for producing 3-acetyl-cyclodextrin, which is eliminated and then desilylated. 6. A method for producing 6-acetyl-cyclodextrin, comprising reacting cyclodextrin with N-acetylimidazole. 7. A method for producing 6-acetyl-cyclodextrin by reacting cyclodextrin with acetyl chloride. 8. A diacetylcyclodextrin derivative represented by the following formula (4) or (5). Embedded image 9. A method according to claim 6, wherein (6-O-t-butyldimethylsilyl) cyclodextrin in which the hydroxyl group at the 2-position is benzylated or allylated is desilylated and then acetylated.
-A process for producing diacetylcyclodextrin. 10. Desilylation after benzylation, allylation or pyranylation of the 3-position hydroxyl group of (6-O-t-butyldimethylsilyl) cyclodextrin in which the 2-position hydroxyl group is benzylated or allylated. A benzyl group or an allyl group at the 2-position and then acetylation. 11. A method wherein benzylation, allylation or pyranylation of the hydroxyl group at the 3-position of (2,6-di-O-tert-butyldimethylsilyl) cyclodextrin is performed, followed by desilylation, followed by acetylation. A method for producing 2,6-diacetylcyclodextrin.