JP3553989B2 - Novel glycosyl donor and method for producing glycoside compound using the same - Google Patents

Description

【００１８】
反応させるアルコールとしては周知のアルコールを使用できる。周知のアルコールとしては、脂肪族アルコール、芳香族アルコール、ステロイドアルコール、グリセロール誘導体、糖誘導体、アミノ酸誘導体などの水酸基を有する化合物を使用できる。
【００１９】
脂肪族アルコールとしては、メタノール、エタノール、プロパノール、イソプロパノール、セチルアルコール、ブタノール、エチレングリコール、プロピレングリコールなどを挙げる事ができる。勿論、シクロヘキサノール、メチルシクロヘキサノール、メントール等の環状脂肪族アルコールも使用できる。
【００２０】
芳香族アルコールとしては、フェノール、ｐ−クロロフェノール、ｏ−クロロフェノール、２，４−ジニトロフェノール、ｐ−クレゾール、ｏ−クレゾール、α−ナフトール、β−ナフトール、カテコール、レゾルシノール、ハイドロキノン等を挙げる事ができる。
【００２１】
ステロイドアルコールとしては、コレステロール、コレスタノール、スチグマステロール、エストロン、エストラジオール、テストステロン、アンドロステロン等が挙げられる。
【００２２】
グリセロール誘導体としては、グリセリン及びそのモノアシル体、ジアシル体を挙げる事ができる。ここで、アシル基としてはアセチル、ベンゾイル、パルミチル、ステアリル、オレイル基等を挙げる事ができ、ジアシル体では同一のアシル基であっても、異なるアシル基であっても何等支障はない。これらの誘導体には立体異性体が存在するものがあるが、そのいずれであっても混合物であっても使用できる事は言うまでもない。加えて、一部の水酸基が他の官能基に変換された誘導体をもこれらの範疇に含まれる。例えば、スフィンゴシン誘導体、セラミドなどを挙げる事ができる。
【００２３】
糖誘導体としては、周知の糖を使用できる。すなわち、前述した糖を使用できるが、必ずしもアノマー位がヘミアセタール結合している必要はなく、鎖状の糖誘導体をも使用できる。糖には、数多くの水酸基があるが、反応に関与しない水酸基は全て前述した方法により保護しておく方が望ましいが、反応性などを考慮して、保護基の使用を必要最小限にする事も可能である。
【００２４】
アミノ酸誘導体としては、セリン、スレオニン、ヒドロキシプロリン、ヒドロキシリジン、チロシンなどを挙げる事ができる。これらのアミノ酸には、Ｄ体とＬ体が存在するが、そのいずれでも、また、混合物であっても使用できる事は言うまでもない。また、種々のアミノ酸から誘導したアミノアルコールやペプチドの誘導体を使用できる。これらの使用に際して、アミノ基やカルボキシル基あるいは他の官能基を常法によって保護した誘導体を使用できる事は当然である。
【００２５】
次に共存させる活性化剤について述べる。活性化剤としては、過塩素酸塩あるいはトリフルオロメタンスルホン酸塩のいずれかを使用する。
【００２６】
過塩素酸塩としては、周知の塩を使用できる。具体的には、過塩素酸銀、過塩素酸リチウム、過塩素酸トリチルなどを挙げる事ができる。とりわけ、過塩素酸トリチルが有効である。過塩素酸トリチルを使用する際にヨウ素を添加させると収率の向上につながる。ヨウ素の使用量は過塩素酸トリチルに対して、０．０１当量〜数当量の範囲であるが、通常０．１〜１．０当量使用する。
【００２７】
トリフルオロメタンスルホン酸塩としては周知の塩を挙げる事ができる。例えば、トリフルオロメタンスルホン酸銀、トリフルオロメタンスルホン酸銅、トリフルオロメタンスルホン酸スズ、トリフルオロメタンスルホン酸リチウムなどを挙げる事ができる。これらの塩の金属の価数は問わない。しかし、トリフルオロメタンスルホン酸スズ（ＩＩ）が優れている。また、トリフルオロメタンスルホン酸スズ（ＩＩ）を使用する際に過塩素酸リチウムを添加すると収率の向上が認められる。ここで、過塩素酸リチウムの使用量は０．０１〜数当量の範囲であるが、通常、０．１〜１．０当量使用する。
【００２８】
反応に用いる溶媒としては、特に制限はない。具体的には、アルコール系の溶媒を除く前述した周知の溶媒を挙げる事ができる。
【００２９】
反応温度としても特に制限はない。しかし、通常、−８０℃から溶媒の沸点の範囲である。また、操作性等を考慮すると−１０℃〜室温の範囲が好ましい。
【００３０】
用いるグリコシル供与体とアルコール及び活性化剤の当量関係にも特に大きな制限はない。例えば、グリコシル供与体あるいはアルコールを過剰に使用する事も可能であるが、両者を等量使用する事も可能である。一方、活性化剤は、その種類にもよるが、通常０．０１〜数等量使用する。好ましくは０．１〜１．０当量で、特に触媒量で使用できる点が本法の利点の一つでもある。
【００３１】
反応時間は反応させる糖やアルコールの構造によっても異なるが、通常数分から数十時間の範囲である。
【００３２】
【発明の効果】
本発明方法によるグリコシド系化合物の製造法は、グリコシル供与体が安定で調製が容易である事、反応性が高く供与体とアルコールのモル比をほぼ等量にしても収率が高い事、また、活性化剤や溶媒等の組み合わせを適宜変える事により生成するグリコシドのアノマーの立体も制御できるなどの利点を有しており、従来の方法における問題点を克服している。従って、本発明の工業的価値は大きい。
【００３３】
以下に実施例を挙げて本発明を更に具体的に説明するが、本発明はその要旨を超えない限り、以下の実施例により何等制限を受けるものではない。
【００３４】
【実施例１】
２，３，４，６−テトラ−Ｏ−ベンジル−Ｄ−グルコピラノース（１．０１３ｇ，１．９ｍｍｏｌ）をテトラヒドロフラン（ＴＨＦ）（１０ｍｌ）に溶解し、−４０℃にて１．６８Ｍ ｎ−ブチルリチウム（１．２６ ｍｌ，２．０６ｍｍｏｌ）を加え、同温度で３０分間攪拌した。これに塩化３−メチルチオプロピオニル（２８６ｍｇ， ２．０６ｍｍｏｌ）をＴＨＦ（１ｍｌ）に溶解して加えた。−４０℃で５時間攪拌後、反応溶液に４％クエン酸水溶液を加え、酢酸エチルで抽出した。常法に従い、洗浄、乾燥、濃縮後、シリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝１５：１）で精製したところ、α体が６０％、β体が２９％得られた。^１３Ｃ ＮＭＲ（ＣＤＣｌ_３） δ＝９０．２（Ｃ−１， β）， ９４．１（Ｃ−１， α）．
【００３５】
【実施例２】
実施例１で合成したグリコシル供与体のβ体（５０ ｍｇ， ０．０７８ｍｍｏｌ）をエーテル１ｍｌに溶解し、ヨウ素の０．１Ｍエーテル溶液（７７８ μｌ， ０．０７８ｍｍｏｌ）を室温で加え、１時間攪拌した後にエーテルを減圧留去した。これを再びエーテル１ｍｌに溶解し、０℃にて過塩素酸トリチル（１５ｍｇ， ０．０３９ｍｍｏｌ）と３β−コレスタノール（３１ ｍｇ， ０．０７８ ｍｍｏｌ）をエーテル１ｍｌを用いて加えた。一晩かけて室温まで昇温させ、５％チオ硫酸ナトリウム水溶液を加えた。常法に従い、酢酸エチルで抽出し、調製用シリカゲル薄層クロマトグラフィー（ヘキサン：酢酸エチル＝６：１）で精製したところ、目的とするグリコシド系化合物を収率８７％、α：β＝８．４：１で得た。
【００３６】
【実施例３】
実施例１で合成したグリコシル供与体のα体（５０ ｍｇ， ０．０７８ ｍｍｏｌ）をエーテル１ｍｌに溶解し、これに、過塩素酸トリチル（１５ ｍｇ，０．０３９ｍｍｏｌ）と３β−コレスタノール（３１ ｍｇ， ０．０７８ ｍｍｏｌ）をエーテル１ｍｌを用いて加えた。一晩かけて室温まで昇温させ、飽和炭酸水素ナトリウム水溶液を加えた。以下、実施例２と同様に行い、目的物を収率７１％、α：β＝８．７：１で得た。
【００３７】
【実施例４】
実施例１で合成したグリコシル供与体のβ体（５０ ｍｇ， ０．０７８ ｍｍｏｌ）とシクロヘキサノール（８ｍｇ， ０．０７８ｍｍｏｌ）をアセトニトリル１ｍｌに溶解し、これに、０℃でトリフルオロメタンスルホン酸スズ（ＩＩ）（３２ｍｇ， ０．０７８ ｍｍｏｌ）と過塩素酸リチウム（１ｍｇ， ０．００８ ｍｍｏｌ）を加え、９０分間攪拌した。以下実施例３と同様に行い、目的とするグリコシド系化合物を収率８５％，α：β＝１：３．９で得た。
【００３８】
【実施例５】
実施例３と同様に、シクロヘキサノール、メチル ２，３，４−トリ−Ｏ−ベンジル−α−Ｄ−グルコピラノシド、メチル ２，３，６−トリ−Ｏ−ベンジル−α−Ｄ−グルコピラノシド、１，６−アンヒドロ−３，４−Ｏ−イソプロピリデン−β−Ｄ−ガラクトピラノース、１，２：３，４−ジ−Ｏ−イソプロピリデン−α−Ｄ−ガラクトピラノースと反応させた。その結果、収率とアノマー比（α：β）は９７％（６．７：１）、７１％（８．７：１）、４６％（４．５：１）、６１％（５．２：１）、８５％（５．２：１）となった。
【００３９】
【実施例６】
実施例４と同様に、メチル ２，３，４−トリ−Ｏ−ベンジル−α−Ｄ−グルコピラノシド、メチル ２，３，６−トリ−Ｏ−ベンジル−α−Ｄ−グルコピラノシド、１，６−アンヒドロ−３，４−Ｏ−イソプロピリデン−β−Ｄ−ガラクトピラノース、１，２：３，４−ジ−Ｏ−イソプロピリデン−α−Ｄ−ガラクトピラノースと反応させた。その結果、収率とアノマー比（α：β）は７４％（１：９．０）、４２％（１：９．２）、６１％（１：１．１）、９４％（１：８．９）となった。[0001]
Summary of the Invention
The present invention relates to a novel glycosyl donor, a method for producing the same, and a method for producing a glycoside compound using the same. Specifically, a glycosyl donor in which hydrogen of a hydroxyl group at an anomeric position of a sugar is substituted with a 3-methylthiopropionyl group, a method for producing the same, and an aliphatic alcohol, an aromatic alcohol, a steroid alcohol, a glycerol derivative, a sugar derivative, an amino acid The present invention relates to a process for producing a glycoside compound, which comprises reacting an alcohol selected from a derivative with an activator selected from a perchlorate and a trifluoromethanesulfonate, and reacting the alcohol.
[0002]
[Industrial applications]
Glycoside-based compounds are attracting attention for use in medicines and agricultural chemicals as antibiotics and anticancer drugs, but recently it has been revealed that they are closely related to cell adhesion and differentiation, and they have been developed as new medicines. Is expected.
[0003]
[Prior art]
Due to the use of unstable intermediates in the synthesis, industrially superior methods are limited. A method known for a long time involves reacting a halogeno sugar with an alcohol, but it has many drawbacks such as poor stability of the raw material halogeno sugar and highly dehydrated reaction conditions, and industrialization is difficult.
[0004]
[Problems to be solved by the invention]
Although a method using an anomeric thiophosphinic acid ester derivative has already been disclosed (JP-A-60-136591), there is a need for the development of a cheaper and more stable glycosyl donor and a method for stereoselectively producing glycoside compounds. Have been. The present inventors have conducted intensive studies in view of the above circumstances, and found that the use of a specific acyl group as a leaving group can solve the stereoselective glycosylation reaction and the stability of a glycosyl donor at once. Reached.
[0005]
[Summary of the Invention]
That is, the gist of the present invention is to provide a glycosyl donor in which the hydrogen of the hydroxyl group at the anomeric position of the sugar is substituted with a 3-methylthiopropionyl group, a method for producing the glycosyl donor, the present glycosyl donor, an aliphatic alcohol, an aromatic alcohol, and a steroid. An alcohol selected from alcohol, glycerol derivative, sugar derivative and amino acid derivative is allowed to coexist with an activator selected from perchlorate and trifluoromethanesulfonate, and reacted to produce a glycoside compound. is there.
[0006]
[Means for Solving the Problems]
Hereinafter, the present invention will be described in detail.
[0007]
First, a method for producing a novel glycosyl donor, one of the present invention, will be described.
[0008]
The novel glycosyl donor, ie, glycosyl 3-methylthiopropionate, can be synthesized by a conventional method from a sugar having a free anomeric hydroxyl group and a 3-methylthiopropionyl halide in the presence of a base.
[0009]
Well-known sugars can be used. The anomeric position of these sugars must be hemiacetal bonded. The cyclic hemiacetal may be a 5- or 6-membered ring. Usually, aldose is used, but ketose can also be used. Specifically, as these sugars, hexoses such as tetraose such as erythrose and threose, pentoses such as ribose, arabinose and xylose, glucose, mannose, galactose, allose and talose, and 2-deoxyglucose , 2-deoxyribose, etc., a part of these sugars are deoxylated or amino sugars, such as 2-acetamido-2-deoxyglucose, and further, these sugars are mutually ether-bonded, such as lactose. Oligosaccharides, sialic acid, glucuronic acid and the like. In addition, these sugars have a D-form and an L-form, and any of them can be used as a mixture.
[0010]
Needless to say, these sugars can be used while protecting all the hydroxyl groups other than the anomeric position, but derivatives having free hydroxyl groups which are protected to the minimum necessary for solubility and the like may be used.
[0011]
As the protecting group for the hydroxyl group, a conventionally well-known group can be used. Specifically, acetyl, trifluoroacetyl, trichloroacetyl, benzoyl, a method of protecting with an acyl group such as p-nitrobenzoyl group, acetaldehyde, a method of acetalization with acetone, etc., methyl, benzyl, triphenylmethyl group and the like Examples thereof include a method of etherification with an alkyl group, a method of silylation with a t-butyldimethylsilyl group, a t-butyldiphenylsilyl group, and the like.
[0012]
On the other hand, known derivatives can be used as the 3-methylthiopropionyl halide. Usually chloride is used.
[0013]
Well-known bases can be used. Specifically, alkali metals such as metal sodium and metal potassium, metal alcoholates such as sodium methoxide and thallium ethoxide, alkali metal hydrides such as sodium hydride, and alkyls such as n-butyllithium and phenyllithium Or aryl metals or tertiary amines such as pyridine, triethylamine, and 1,8-diazabicyclo- [5,4,0] -undec-7-ene.
[0014]
As the solvent, a solvent other than alcohols can be used. That is, benzene, toluene, chloroform, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, ether, tetrahydrofuran, dimethylformamide, acetonitrile, propionitrile, nitromethane and the like can be mentioned.
[0015]
The reaction temperature is not particularly limited. Usually, the temperature ranges from -60 ° C to the boiling point of the solvent, preferably from -10 ° C to room temperature.
[0016]
The 3-methylthiopropionyl halide and the base can be used in a large excess with respect to the sugar, but are usually used in a molar amount of 1 to 2 times. Preferably, it is about 1 to 1.2 equivalents.
[0017]
Next, a method for producing a glycoside compound will be described. The above-mentioned glycosyl donor and alcohol are reacted in the presence of an activator.
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[0018]
As the alcohol to be reacted, a known alcohol can be used. As the well-known alcohol, a compound having a hydroxyl group such as an aliphatic alcohol, an aromatic alcohol, a steroid alcohol, a glycerol derivative, a sugar derivative, and an amino acid derivative can be used.
[0019]
Examples of the aliphatic alcohol include methanol, ethanol, propanol, isopropanol, cetyl alcohol, butanol, ethylene glycol, propylene glycol and the like. Of course, cyclic aliphatic alcohols such as cyclohexanol, methylcyclohexanol and menthol can also be used.
[0020]
Examples of the aromatic alcohol include phenol, p-chlorophenol, o-chlorophenol, 2,4-dinitrophenol, p-cresol, o-cresol, α-naphthol, β-naphthol, catechol, resorcinol, hydroquinone, and the like. Can be.
[0021]
Examples of the steroid alcohol include cholesterol, cholestanol, stigmasterol, estrone, estradiol, testosterone, androsterone, and the like.
[0022]
Examples of the glycerol derivative include glycerin and its monoacyl and diacyl derivatives. Here, examples of the acyl group include acetyl, benzoyl, palmityl, stearyl, and oleyl groups. In the case of a diacyl derivative, the same acyl group or different acyl groups cause no problem. Some of these derivatives have stereoisomers, and it goes without saying that any of these derivatives and mixtures thereof can be used. In addition, derivatives in which some hydroxyl groups are converted to other functional groups are also included in these categories. For example, sphingosine derivatives, ceramides and the like can be mentioned.
[0023]
Well-known sugars can be used as the sugar derivatives. That is, the above-mentioned sugar can be used, but the anomeric position does not necessarily have to be hemiacetal-bonded, and a chain-like sugar derivative can also be used. Sugars have many hydroxyl groups, but it is desirable to protect all hydroxyl groups that do not participate in the reaction by the above-mentioned method.However, considering the reactivity etc., minimize the use of protecting groups as necessary. Is also possible.
[0024]
Examples of amino acid derivatives include serine, threonine, hydroxyproline, hydroxylysine, tyrosine and the like. These amino acids have a D-form and an L-form, and it goes without saying that any of them and even a mixture can be used. In addition, derivatives of amino alcohols and peptides derived from various amino acids can be used. When these are used, it is natural that a derivative in which an amino group, a carboxyl group, or another functional group is protected by a conventional method can be used.
[0025]
Next, the co-activator will be described. As the activator, either perchlorate or trifluoromethanesulfonate is used.
[0026]
As the perchlorate, a known salt can be used. Specific examples include silver perchlorate, lithium perchlorate, and trityl perchlorate. In particular, trityl perchlorate is effective. Addition of iodine when using trityl perchlorate leads to an improvement in yield. The amount of iodine used is in the range of 0.01 equivalent to several equivalents to trityl perchlorate, but usually 0.1 to 1.0 equivalent is used.
[0027]
Well-known salts can be mentioned as the trifluoromethanesulfonate. For example, silver trifluoromethanesulfonate, copper trifluoromethanesulfonate, tin trifluoromethanesulfonate, lithium trifluoromethanesulfonate and the like can be mentioned. The metal valence of these salts does not matter. However, tin (II) trifluoromethanesulfonate is superior. When tin (II) trifluoromethanesulfonate is used, addition of lithium perchlorate improves the yield. Here, the amount of lithium perchlorate used is in the range of 0.01 to several equivalents, but usually 0.1 to 1.0 equivalent is used.
[0028]
The solvent used for the reaction is not particularly limited. Specifically, there may be mentioned the above-mentioned well-known solvents excluding alcohol-based solvents.
[0029]
There is no particular limitation on the reaction temperature. However, it is usually in the range of -80 ° C to the boiling point of the solvent. Further, in consideration of operability and the like, the range is preferably −10 ° C. to room temperature.
[0030]
There is no particular limitation on the equivalent relationship between the glycosyl donor used, the alcohol and the activator. For example, it is possible to use an excess of a glycosyl donor or an alcohol, but it is also possible to use an equal amount of both. On the other hand, the activator is usually used in an amount of 0.01 to several equivalents, depending on the type. One of the advantages of the present method is that it can be preferably used in an amount of 0.1 to 1.0 equivalent, particularly in a catalytic amount.
[0031]
The reaction time varies depending on the structure of the sugar or alcohol to be reacted, but usually ranges from several minutes to several tens of hours.
[0032]
【The invention's effect】
The method for producing a glycoside compound according to the method of the present invention is that the glycosyl donor is stable and easy to prepare, the reactivity is high and the yield is high even when the molar ratio of the donor and the alcohol is almost equal, and It has the advantage that the steric nature of the glycoside anomer can be controlled by appropriately changing the combination of the activator, the solvent and the like, thereby overcoming the problems of the conventional methods. Therefore, the industrial value of the present invention is great.
[0033]
Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited by the following examples unless it exceeds the gist thereof.
[0034]
Embodiment 1
2,3,4,6-Tetra-O-benzyl-D-glucopyranose (1.013 g, 1.9 mmol) was dissolved in tetrahydrofuran (THF) (10 ml), and -40 ° C at 1.68 M n-butyl. Lithium (1.26 ml, 2.06 mmol) was added, and the mixture was stirred at the same temperature for 30 minutes. To this was added 3-methylthiopropionyl chloride (286 mg, 2.06 mmol) dissolved in THF (1 ml). After stirring at -40 ° C for 5 hours, a 4% aqueous citric acid solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. After washing, drying and concentration according to a conventional method, purification by silica gel column chromatography (hexane: ethyl acetate = 15: 1) gave 60% α-form and 29% β-form. ¹³ C NMR (CDCl ₃ ) δ = 90.2 (C-1, β), 94.1 (C-1, α).
[0035]
Embodiment 2
The β-form (50 mg, 0.078 mmol) of the glycosyl donor synthesized in Example 1 was dissolved in 1 ml of ether, a 0.1 M ether solution of iodine (778 μl, 0.078 mmol) was added at room temperature, and the mixture was stirred for 1 hour. After that, ether was distilled off under reduced pressure. This was dissolved again in 1 ml of ether, and trityl perchlorate (15 mg, 0.039 mmol) and 3β-cholestanol (31 mg, 0.078 mmol) were added at 0 ° C. using 1 ml of ether. The temperature was raised to room temperature overnight, and a 5% aqueous sodium thiosulfate solution was added. Extraction with ethyl acetate and purification by silica gel thin-layer chromatography (hexane: ethyl acetate = 6: 1) according to a conventional method gave the target glycoside compound in a yield of 87% and α: β = 8. Obtained 4: 1.
[0036]
Embodiment 3
The α-isomer (50 mg, 0.078 mmol) of the glycosyl donor synthesized in Example 1 was dissolved in 1 ml of ether, and trityl perchlorate (15 mg, 0.039 mmol) and 3β-cholestanol (31 mg, 0.078 mmol) was added using 1 ml of ether. The temperature was raised to room temperature overnight, and a saturated aqueous solution of sodium hydrogen carbonate was added. Thereafter, the same procedure as in Example 2 was carried out to obtain the desired product at a yield of 71% and α: β = 8.7: 1.
[0037]
Embodiment 4
The β-form (50 mg, 0.078 mmol) of the glycosyl donor synthesized in Example 1 and cyclohexanol (8 mg, 0.078 mmol) were dissolved in 1 ml of acetonitrile, and tin trifluoromethanesulfonate (0 ° C.) was added thereto. II) (32 mg, 0.078 mmol) and lithium perchlorate (1 mg, 0.008 mmol) were added, and the mixture was stirred for 90 minutes. Thereafter, the same procedure as in Example 3 was carried out to obtain a target glycoside compound at a yield of 85% and α: β = 1: 3.9.
[0038]
Embodiment 5
As in Example 3, cyclohexanol, methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside, methyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside, It was reacted with 6-anhydro-3,4-O-isopropylidene-β-D-galactopyranose, 1,2,3,4-di-O-isopropylidene-α-D-galactopyranose. As a result, the yield and the anomeric ratio (α: β) were 97% (6.7: 1), 71% (8.7: 1), 46% (4.5: 1), and 61% (5.2). : 1), 85% (5.2: 1).
[0039]
Embodiment 6
As in Example 4, methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside, methyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside, 1,6-anhydro -3,4-O-isopropylidene-β-D-galactopyranose, 1,2,3,4-di-O-isopropylidene-α-D-galactopyranose. As a result, the yield and anomeric ratio (α: β) were 74% (1: 9.0), 42% (1: 9.2), 61% (1: 1.1), and 94% (1: 8). .9).

Claims (7)

General formalized 1 (wherein R is _{-H, -CH 3, -CH 2 OH} , -OH, -OCH 2 Ph, -OCOCH 3, -OCH 3, -CH 2 OCH 3, -CH 2 OCPh 3, - CH ₂ OCH ₂ Ph, —CH ₂ OCOCH ₃ , —NHCOCH ₃ , or —OC (CH ₃ ) ₂ O—, —OCH (Ph) O— in which R and R are bonded, wherein Ph represents a phenyl group ..) indicates one of) or general formalized 2 (wherein R is _{-H, -CH 3, -CH 2 OH} , -OH, -CH (OH) CH 2 OH, -OCH 2 Ph, - _{OCOCH 3, -OCH 3, -CH 2} OCH 3, -CH 2 OCPh 3, -CH 2 OCH 2 Ph, -CH 2 OCOCH 3, -NHCOCH 3, -CH (OCH 2 Ph) CH 2 OCH 2 Ph, - CH (OCOC _{3) CH 2 OCOCH 3, -CHOHCH} 2 OCPh 3, Formula 3, Formula 4 or, _-OC which R and R are bonded _{(CH 3) 2 O -,} - OCH (Ph) O- ( where, Ph is phenyl A glycosyl donor wherein the hydrogen of the hydroxyl group at the anomeric position of the saccharide represented by) is substituted with a 3-methylthiopropionyl group.

General formalized 1 (wherein R _{-H, -CH} 3 of the anomeric hydroxyl group and a halogenated 3-methyl thio propionyl sugar, characterized in that to the base coexistence reaction, -CH 2 OH, -OH, -OCH ₂ Ph, —OCOCH ₃ , —OCH ₃ , —CH ₂ OCH ₃ , —CH ₂ OCPh ₃ , —CH ₂ OCH ₂ Ph, —CH ₂ OCOCH ₃ , —NHCOCH ₃ , or —OC in which R and R are bonded. (CH ₃ ) ₂ O—, —OCH (Ph) O— (wherein, Ph represents a phenyl group) or general formula 2 (where R is —H, —CH _{3). , -CH 2 OH, -OH, -CH} (OH) CH 2 OH, -OCH 2 Ph, -OCOCH 3, -OCH 3, -CH 2 OCH 3, -CH 2 OCPh 3, -CH 2 OCH 2 Ph, -CH ₂ O _{COCH 3, -NHCOCH 3, -CH (} OCH 2 Ph) CH 2 OCH 2 Ph, -CH (OCOCH 3) CH 2 OCOCH 3, -CHOHCH 2 OCPh 3, Formula 3, Formula 4 or, R and R are bonded _{-OC (CH 3) 2 O -} , -. OCH (Ph) O- ( where. However, Ph is showing a phenyl group), one of) the hydrogen of the hydroxyl groups of the anomeric position of the sugar represented by 3-methylthio A method for producing a glycosyl donor substituted with a propionyl group. General formalized 1 (wherein R is _{-H, -CH 3, -CH 2 OH} , -OH, -OCH 2 Ph, -OCOCH 3, -OCH 3, -CH 2 OCH 3, -CH 2 OCPh 3, - CH ₂ OCH ₂ Ph, —CH ₂ OCOCH ₃ , —NHCOCH ₃ , or —OC (CH ₃ ) ₂ O—, —OCH (Ph) O— in which R and R are bonded, wherein Ph represents a phenyl group ..) indicates one of) or general formalized 2 (wherein R is _{-H, -CH 3, -CH 2 OH} , -OH, -CH (OH) CH 2 OH, -OCH 2 Ph, - _{OCOCH 3, -OCH 3, -CH 2} OCH 3, -CH 2 OCPh 3, -CH 2 OCH 2 Ph, -CH 2 OCOCH 3, -NHCOCH 3, -CH (OCH 2 Ph) CH 2 OCH 2 Ph, - CH (OCOC _{3) CH 2 OCOCH 3, -CHOHCH} 2 OCPh 3, Formula 3, Formula 4 or, _-OC which R and R are bonded _{(CH 3) 2 O -,} - OCH (Ph) O- ( where, Ph is phenyl A) a glycosyl donor in which the hydrogen of the hydroxyl group at the anomeric position of the sugar represented by) is substituted with a 3-methylthiopropionyl group, and an aliphatic alcohol, an aromatic alcohol, a steroid alcohol, or a glycerol derivative. A method for producing a glycoside compound, comprising reacting an alcohol selected from a sugar derivative and an amino acid derivative with an activator selected from a perchlorate and a trifluoromethanesulfonate, and reacting the same. 4. The method according to claim 3, wherein trityl perchlorate is used as the activator. 4. The method according to claim 3, wherein tin (II) trifluoromethanesulfonate is used as the activating agent. 5. The method according to claim 4, wherein iodine coexists. 6. The method according to claim 5, wherein lithium perchlorate is allowed to coexist.