JP4679981B2 - Method for deprotecting 9-fluorenylmethoxycarbonyl group - Google Patents

Method for deprotecting 9-fluorenylmethoxycarbonyl group Download PDF

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JP4679981B2
JP4679981B2 JP2005193336A JP2005193336A JP4679981B2 JP 4679981 B2 JP4679981 B2 JP 4679981B2 JP 2005193336 A JP2005193336 A JP 2005193336A JP 2005193336 A JP2005193336 A JP 2005193336A JP 4679981 B2 JP4679981 B2 JP 4679981B2
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JP2007008887A (en
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弘尚 佐治木
智弘 前川
耕作 廣田
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NE Chemcat Corp
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Description

本発明は、水素存在下パラジウムカーボン触媒を用いることによる9−フルオレニルメトキシカルボニル基の脱保護基方法に関する。   The present invention relates to a method for deprotecting a 9-fluorenylmethoxycarbonyl group by using a palladium carbon catalyst in the presence of hydrogen.

9−フルオレニルメトキシカルボニル基（以下Fmoc基と呼ぶ）は、ペプチド合成等におけるアミノ酸等のアミノ基の保護基等として広く用いられており、通常、その脱保護基法には、ピペリジン等の塩基が用いられる（例えば、非特許文献１及び非特許文献２）。しかしながら、塩基の使用によるFmoc基の脱保護基法においては、保護されている基質が分解することや塩基との分離が煩雑である等の問題点がある。   The 9-fluorenylmethoxycarbonyl group (hereinafter referred to as Fmoc group) is widely used as a protecting group for amino groups such as amino acids in peptide synthesis and the like. Usually, the deprotecting group method includes piperidine and the like. A base is used (for example, Non-Patent Document 1 and Non-Patent Document 2). However, the Fmoc group deprotection method using a base has problems such as decomposition of the protected substrate and complicated separation from the base.

一方、水素ガス供給下パラジウムカーボン触媒を用いて、Fmoc基を脱保護基する方法は知られている（非特許文献３）。この場合、脱保護基反応は酢酸酸性で行われるが、25時間後でも反応は完結せず、40%程度しか脱保護されないという問題点がある。   On the other hand, a method for deprotecting the Fmoc group using a palladium carbon catalyst under hydrogen gas supply is known (Non-patent Document 3). In this case, the deprotecting group reaction is carried out with acetic acid, but the reaction is not completed even after 25 hours, and there is a problem that only about 40% is deprotected.

J. Chem. Soc. Perkin. Trans. 1, 1981, 538-546J. Chem. Soc. Perkin. Trans. 1, 1981, 538-546 J. Org. Chem. 1983, 666-669J. Org. Chem. 1983, 666-669 Tetrahedron Lett., 1979, 32, 3041-3042Tetrahedron Lett., 1979, 32, 3041-3042

そこで、本発明の課題は、分離の煩雑さの原因となる塩基を実質的に使用せず、基質の分解を抑制し、高収率にてFmoc基を脱保護する脱保護基法を提供することにある。   Thus, an object of the present invention is to provide a deprotecting group method that substantially eliminates bases that cause separation complexity, suppresses decomposition of the substrate, and deprotects the Fmoc group in high yield. There is.

本発明者らは、パラジウム系触媒を鋭意検討した結果、比表面積1000m2/g以上の炭素粒子にパラジウムを固定したパラジウムカーボン触媒を用いると、実質的に塩基を使用せずとも、水素存在下で、Fmoc基が効率的に脱保護されることを見出し、本発明を完成するに至った。 As a result of intensive studies on palladium-based catalysts, the present inventors have found that when a palladium carbon catalyst in which palladium is fixed to carbon particles having a specific surface area of 1000 m 2 / g or more is used, the presence of hydrogen is substantially eliminated without using a base. Thus, the inventors have found that the Fmoc group can be efficiently deprotected, and have completed the present invention.

すなわち、本発明は、9−フルオレニルメトキシカルボニル基（Fmock基）で保護された基質を、比表面積1000m2/g以上の炭素粒子にパラジウムを固定したパラジウムカーボン触媒の存在下で、水素と湿式で接触させることを特徴とするFmock基の脱保護基方法を提供するものである。 That is, the present invention provides a substrate protected with a 9-fluorenylmethoxycarbonyl group (Fmock group) in the presence of a palladium carbon catalyst in which palladium is fixed to carbon particles having a specific surface area of 1000 m 2 / g or more. An object of the present invention is to provide a method for deprotecting an Fmock group, which is performed by wet contact.

本発明の脱保護基方法によれば、実質的に塩基を使用せずに、かつ比較的短時間で高収率でFmoc基を効率的に脱保護することができる。   According to the deprotecting group method of the present invention, the Fmoc group can be efficiently deprotected in a high yield in a relatively short time without substantially using a base.

以下、本発明について更に詳細に説明する。   Hereinafter, the present invention will be described in more detail.

本発明のFmoc基の脱保護基方法は、Fmock基で保護された反応性基を有する基質を水素と比表面積1000m2/g以上の炭素粒子にパラジウムを固定したパラジウムカーボン触媒の存在下で接触させる。 In the Fmoc group deprotection group method of the present invention, a substrate having a reactive group protected by an Fmock group is contacted with hydrogen in the presence of a palladium carbon catalyst in which palladium is fixed to carbon particles having a specific surface area of 1000 m 2 / g or more. Let

本発明の脱保護基方法の反応の目的物となるFmoc基によって保護された反応性基、例えばアミノ基、を含有する化合物（基質）としては、特に限定するものではないが、例えばアミノカルボン酸やアミノアルコールなどが挙げられる。アミノカルボン酸の例としては、グリシン、アラニン、バリン、ロイシン、イソロイシン、セリン、トレオニン、システイン、シスチン、メチオニン、アスパラギン、アスパラギン酸、グルタミン、グルタミン酸、リシン、アルギニン、フェニルアラニン、チロシン、ヒスチジン、トリプトファン、プロリン、オキシプロリン、Ｏ−メチルセリン、ピバル酸セリンエステル、Ｏ−（第三ブチルジメチルシリル）セリンなどのαアミノ酸、β−ホモフェニルアラニンなどのβアミノ酸、４−アミノブタン酸などのγアミノ酸などが挙げられる。また、アミノアルコールの例としては３−アミノ−１−プロパノール、４−アミノ−１−ブタノールなどが挙げられる。   A compound (substrate) containing a reactive group protected by an Fmoc group, for example, an amino group, which is a target of the reaction of the deprotecting group method of the present invention, is not particularly limited. For example, an aminocarboxylic acid And amino alcohol. Examples of aminocarboxylic acids include glycine, alanine, valine, leucine, isoleucine, serine, threonine, cysteine, cystine, methionine, asparagine, aspartic acid, glutamine, glutamic acid, lysine, arginine, phenylalanine, tyrosine, histidine, tryptophan, proline. , Oxyproline, O-methylserine, pivalic acid serine ester, α-amino acid such as O- (tert-butyldimethylsilyl) serine, β-amino acid such as β-homophenylalanine, and γ-amino acid such as 4-aminobutanoic acid. Examples of amino alcohols include 3-amino-1-propanol and 4-amino-1-butanol.

また、これら目的物となるアミノ基含有化合物には置換基がついていてもよく、Ｆｍｏｃ基以外の保護基が、Fmoc基によって保護されたアミノ基以外にあっても差し支えない。   In addition, the amino group-containing compound to be the target product may have a substituent, and the protecting group other than the Fmoc group may be other than the amino group protected by the Fmoc group.

本発明の脱保護基方法は湿式で、即ち、溶媒中で行なわれる。これに用いられる溶媒には、特に限定するものではないが、水、メタノール、エタノール、アセトニトリル、酢酸、テトラヒドロフランまたはこれらの混合溶媒が好適であり、メタノールとアセトニトリルの混合溶媒が特に好適である。   The deprotecting method of the present invention is carried out wet, i.e. in a solvent. The solvent used for this is not particularly limited, but water, methanol, ethanol, acetonitrile, acetic acid, tetrahydrofuran, or a mixed solvent thereof is preferable, and a mixed solvent of methanol and acetonitrile is particularly preferable.

本発明の脱保護基方法の反応温度は特に限定するものではないが、室温（２０℃、以下同じ）から溶媒として用いる化合物の沸点までの温度範囲が好適であり、室温から50℃までが特に好適である。   The reaction temperature of the deprotecting group method of the present invention is not particularly limited, but a temperature range from room temperature (20 ° C., the same shall apply hereinafter) to the boiling point of the compound used as a solvent is preferable, and room temperature to 50 ° C. is particularly preferable. Is preferred.

また、本発明の脱保護基方法において水素の存在は必須である。水素は遊離の状態の水素であり、通常、水素ガスとして反応中にあるいは反応に先んじて反応系に供給すればよい。例えば、攪拌下の反応液の上部気相部に供給してもよいし、通気してもよい。水素は例えば窒素などの不活性気体との混合ガスとして供給してもよい。供給された水素の圧力は特に限定するものではないが、水素分圧として0.05〜100気圧が好適であり、1〜10気圧が特に好適である。   In addition, the presence of hydrogen is essential in the deprotecting method of the present invention. Hydrogen is hydrogen in a free state, and is usually supplied to the reaction system during the reaction or prior to the reaction as hydrogen gas. For example, it may be supplied to the upper gas phase portion of the reaction liquid under stirring or aerated. Hydrogen may be supplied as a mixed gas with an inert gas such as nitrogen. The pressure of the supplied hydrogen is not particularly limited, but the hydrogen partial pressure is preferably 0.05 to 100 atm, and particularly preferably 1 to 10 atm.

本発明の脱保護基方法において用いられるパラジウムカーボン触媒は比表面積1000m2/g以上、好ましくは1050m2/g以上、より好ましくは1100〜1500m2/gの炭素粒子にパラジウムを固定したものである。支持体である炭素粒子の比表面積が1000m2/g未満であると、本発明の効果は得がたい。パラジウムカーボン触媒のパラジウム含有率は特に限定するものではないが、1〜50重量％が好適であり、5〜20重量％が特に好適である。また、パラジウムカーボン触媒の形状は特に限定するものではないが、粉末状または顆粒状が好適であり、粉末状が特に好適である。使用した触媒はろ過等の簡便な方法で、目的物を含む溶液から容易に分離することができる。 Palladium on carbon catalyst used in the deprotection process of the present invention the specific surface area of 1000 m 2 / g or more, preferably 1050 m 2 / g or more, more preferably with a fixed palladium carbon particles 1100~1500m 2 / g . When the specific surface area of the carbon particles as the support is less than 1000 m 2 / g, the effect of the present invention is difficult to obtain. The palladium content of the palladium carbon catalyst is not particularly limited, but is preferably 1 to 50% by weight, and particularly preferably 5 to 20% by weight. Further, the shape of the palladium carbon catalyst is not particularly limited, but a powder form or a granular form is preferable, and a powder form is particularly preferable. The used catalyst can be easily separated from the solution containing the target product by a simple method such as filtration.

以下に本発明の実施例を示すが、本発明は以下の実施例に限定されるものではない。   Examples of the present invention are shown below, but the present invention is not limited to the following examples.

〔Ｎ−Ｆｍｏｃ−Ｌ−フェニルアラニンの脱保護基〕
Ｎ−Ｆｍｏｃ−Ｌ−フェニルアラニン250μmolをメタノール・アセトニトリルの混合溶媒（重量比80:1）1mlに溶解し、10重量％パラジウムカーボン粉末Ｋ−ｔｙｐｅ（カーボンの比表面積1190m2/g、エヌ・イー ケムキャット社製）10mgを添加した。バルーンによる水素微加圧下室温で24時間反応させた。触媒をろ別後反応液から溶媒を留去しエーテル洗浄して９−メチルフルオレンを除去しＬ−フェニルアラニンを単離した。収率92%。 [Deprotecting group of N-Fmoc-L-phenylalanine]
N-Fmoc-L-phenylalanine 250 μmol was dissolved in 1 ml of a mixed solvent of methanol / acetonitrile (weight ratio 80: 1), and 10% by weight palladium carbon powder K-type (carbon specific surface area 1190 m 2 / g, N.E. Chemcat) 10 mg) was added. The reaction was allowed to proceed for 24 hours at room temperature under slightly pressurized hydrogen using a balloon. After the catalyst was filtered off, the solvent was distilled off from the reaction solution and washed with ether to remove 9-methylfluorene and isolate L-phenylalanine. Yield 92%.

〔Ｎ−Ｆｍｏｃ−Ｌ−フェニルアラニンの脱保護基〕
実施例１においてメタノール・アセトニトリルの混合溶媒の混合比を（重量比15:1）とし、反応時間を13時間とした以外は実施例１と同様にしてＬ−フェニルアラニンを単離した。収率96%。 [Deprotecting group of N-Fmoc-L-phenylalanine]
In Example 1, L-phenylalanine was isolated in the same manner as in Example 1 except that the mixing ratio of the mixed solvent of methanol and acetonitrile was (weight ratio 15: 1) and the reaction time was 13 hours. Yield 96%.

〔Ｎ−Ｆｍｏｃ−Ｌ−セリンの脱保護基〕
実施例１においてＮ−Ｆｍｏｃ−Ｌ−フェニルアラニンの代わりにＮ−Ｆｍｏｃ−Ｌ−セリンを用いる以外は実施例１と同様にしてＬ−セリンを単離した。収率94%。 [Deprotecting group of N-Fmoc-L-serine]
L-serine was isolated in the same manner as in Example 1 except that N-Fmoc-L-serine was used instead of N-Fmoc-L-phenylalanine in Example 1. Yield 94%.

〔Ｎ−Ｆｍｏｃ−Ｌ−セリンの脱保護基〕
実施例１においてＮ−Ｆｍｏｃ−Ｌ−フェニルアラニンの代わりにＮ−Ｆｍｏｃ−Ｌ−セリンを用い、メタノール・アセトニトリルの混合溶媒の混合比を（重量比15:1）とし、反応時間を12時間とした以外は実施例１と同様にしてＬ−セリンを単離した。収率90%。 [Deprotecting group of N-Fmoc-L-serine]
In Example 1, N-Fmoc-L-serine was used instead of N-Fmoc-L-phenylalanine, the mixed ratio of the mixed solvent of methanol and acetonitrile was set to 15: 1, and the reaction time was set to 12 hours. Except for the above, L-serine was isolated in the same manner as in Example 1. Yield 90%.

〔Ｎ−Ｆｍｏｃ−Ｌ−アラニンの脱保護基〕
実施例１においてＮ−Ｆｍｏｃ−Ｌ−フェニルアラニンの代わりにＮ−Ｆｍｏｃ−Ｌ−アラニンを用いる以外は実施例１と同様にしてＬ−アラニンを単離した。収率92%。 [Deprotecting group of N-Fmoc-L-alanine]
L-alanine was isolated in the same manner as in Example 1 except that N-Fmoc-L-alanine was used instead of N-Fmoc-L-phenylalanine in Example 1. Yield 92%.

〔Ｎ−Ｆｍｏｃ−Ｌ−アラニンの脱保護基〕
実施例１においてＮ−Ｆｍｏｃ−Ｌ−フェニルアラニンの代わりにＮ−Ｆｍｏｃ−Ｌ−アラニンを用い、メタノール・アセトニトリルの混合溶媒の混合比を（重量比15:1）とし、反応時間を12時間とした以外は実施例１と同様にしてＬ−セリンを単離した。収率100%。 [Deprotecting group of N-Fmoc-L-alanine]
In Example 1, N-Fmoc-L-Alanine was used instead of N-Fmoc-L-phenylalanine, the mixing ratio of the mixed solvent of methanol and acetonitrile was (weight ratio 15: 1), and the reaction time was 12 hours. Except for the above, L-serine was isolated in the same manner as in Example 1. Yield 100%.

〔Ｎ−Ｆｍｏｃ−Ｌ−アスパラギンの脱保護基〕
実施例１においてＮ−Ｆｍｏｃ−Ｌ−フェニルアラニンの代わりにＮ−Ｆｍｏｃ−Ｌ−アスパラギンを用いる以外は実施例１と同様にしてＬ−アスパラギンを単離した。収率84%。 [Deprotecting group of N-Fmoc-L-asparagine]
L-asparagine was isolated in the same manner as in Example 1 except that N-Fmoc-L-asparagine was used instead of N-Fmoc-L-phenylalanine in Example 1. Yield 84%.

〔Ｎ−Ｆｍｏｃ−Ｌ−リシンの脱保護基〕
実施例１においてＮ−Ｆｍｏｃ−Ｌ−フェニルアラニンの代わりにＮ−Ｆｍｏｃ−Ｌ−リシンを用いる以外は実施例１と同様にしてＬ−リシンを単離した。収率68%。 [Deprotecting group of N-Fmoc-L-lysine]
In Example 1, L-lysine was isolated in the same manner as in Example 1 except that N-Fmoc-L-lysine was used instead of N-Fmoc-L-phenylalanine. Yield 68%.

〔Ｎ−Ｆｍｏｃ−Ｌ−グルタミン酸の脱保護基〕
実施例１においてＮ−Ｆｍｏｃ−Ｌ−フェニルアラニンの代わりにＮ−Ｆｍｏｃ−Ｌ−グルタミン酸を用いる以外は実施例１と同様にしてＬ−グルタミン酸を単離した。収率95%。 [Deprotecting group of N-Fmoc-L-glutamic acid]
L-glutamic acid was isolated in the same manner as in Example 1 except that N-Fmoc-L-glutamic acid was used instead of N-Fmoc-L-phenylalanine in Example 1. Yield 95%.

〔Ｎ−Ｆｍｏｃ−Ｌ−グルタミン酸の脱保護基〕
実施例１においてＮ−Ｆｍｏｃ−Ｌ−フェニルアラニンの代わりにＮ−Ｆｍｏｃ−Ｌ−グルタミン酸を用い、メタノール・アセトニトリルの混合溶媒の混合比を（重量比15:1）とし、反応時間を12時間とした以外は実施例１と同様にしてＬ−グルタミン酸を単離した。収率100%。 [Deprotecting group of N-Fmoc-L-glutamic acid]
In Example 1, instead of N-Fmoc-L-phenylalanine, N-Fmoc-L-glutamic acid was used, the mixing ratio of the mixed solvent of methanol and acetonitrile was (weight ratio 15: 1), and the reaction time was 12 hours. Except for the above, L-glutamic acid was isolated in the same manner as in Example 1. Yield 100%.

〔Ｎ−Ｆｍｏｃ−Ｌ−フェニルアラニンの脱保護基〕
Ｎ−Ｆｍｏｃ−Ｌ−フェニルアラニン250μmolをメタノール溶媒1mlに溶解し、10重量％パラジウムカーボン粉末Ｋ−ｔｙｐｅ（カーボンの比表面積1190m2/g、エヌ・イー ケムキャット社製）10mgを添加した。水素圧３気圧下室温で6時間反応させた。触媒をろ別後反応液から溶媒を留去しヘキサン洗浄して９−メチルフルオレンを除去しＬ−フェニルアラニンを単離した。収率92%。
［比較例１］ [Deprotecting group of N-Fmoc-L-phenylalanine]
250 μmol of N-Fmoc-L-phenylalanine was dissolved in 1 ml of methanol solvent, and 10 mg of 10 wt% palladium carbon powder K-type (specific surface area of carbon 1190 m 2 / g, manufactured by N.E. Chemcat) was added. The reaction was performed at room temperature under a hydrogen pressure of 3 atm for 6 hours. After the catalyst was filtered off, the solvent was distilled off from the reaction solution and washed with hexane to remove 9-methylfluorene and isolate L-phenylalanine. Yield 92%.
[Comparative Example 1]

〔Ｎ−Ｆｍｏｃ−Ｌ−フェニルアラニンの脱保護基〕
Ｎ−Ｆｍｏｃ−Ｌ−フェニルアラニン250μmolをメタノール・アセトニトリルの混合溶媒（重量比80:1）1mlに溶解し、10重量％パラジウムカーボン粉末（カーボンの比表面積920m2/g、エヌ・イー ケムキャット社製）10mgを添加した。バルーンによる水素微加圧下室温で24時間反応させた。触媒をろ別後反応液から溶媒を留去しエーテル洗浄して９−メチルフルオレンを除去しＬ−フェニルアラニンを単離を試みたが、Ｌ−フェニルアラニンは得られなかった。収率0%。
［比較例２］ [Deprotecting group of N-Fmoc-L-phenylalanine]
Dissolve 250 μmol of N-Fmoc-L-phenylalanine in 1 ml of a mixed solvent of methanol / acetonitrile (weight ratio 80: 1), 10 wt% palladium carbon powder (carbon specific surface area 920 m 2 / g, manufactured by N.E. Chemcat) 10 mg was added. The reaction was allowed to proceed for 24 hours at room temperature under slightly pressurized hydrogen using a balloon. After the catalyst was filtered off, the solvent was distilled off from the reaction solution and washed with ether to remove 9-methylfluorene and attempt to isolate L-phenylalanine, but L-phenylalanine was not obtained. Yield 0%.
[Comparative Example 2]

〔Ｎ−Ｆｍｏｃ−Ｌ−フェニルアラニンの脱保護基〕
Ｎ−Ｆｍｏｃ−Ｌ−フェニルアラニン250μmolをメタノール・アセトニトリルの混合溶媒（重量比80:1）1mlに溶解し、10重量％パラジウムカーボン粉末（カーボンの比表面積950m2/g、アルドリッチ社製）10mgを添加した。バルーンによる水素微加圧下室温で24時間反応させた。触媒をろ別後反応液から溶媒を留去しエーテル洗浄して９−メチルフルオレンを除去しＬ−フェニルアラニンを単離を試みたが、Ｌ−フェニルアラニンは得られなかった。収率0%。
［比較例３］ [Deprotecting group of N-Fmoc-L-phenylalanine]
Dissolve 250 μmol of N-Fmoc-L-phenylalanine in 1 ml of a mixed solvent of methanol and acetonitrile (weight ratio 80: 1) and add 10 mg of 10 wt% palladium carbon powder (specific surface area of carbon 950 m 2 / g, manufactured by Aldrich) did. The reaction was allowed to proceed for 24 hours at room temperature under slightly pressurized hydrogen using a balloon. After the catalyst was filtered off, the solvent was distilled off from the reaction solution and washed with ether to remove 9-methylfluorene and attempt to isolate L-phenylalanine, but L-phenylalanine was not obtained. Yield 0%.
[Comparative Example 3]

〔Ｎ−Ｆｍｏｃ−グリシンの脱保護基〕
Ｎ−Ｆｍｏｃ−グリシン250μmolをメタノール・酢酸の混合溶媒（重量比4:1）1mlに溶解し、10重量％パラジウムカーボン粉末（カーボンの比表面積950m2/g、アルドリッチ社製）10mgを添加した。バルーンによる水素微加圧下室温で24時間反応させた。触媒をろ別後反応液を逆相HPLCで分析して、グリシンを同定した。収率40%。 [Deprotecting group of N-Fmoc-glycine]
250 μmol of N-Fmoc-glycine was dissolved in 1 ml of a mixed solvent of methanol and acetic acid (weight ratio 4: 1), and 10 mg of 10 wt% palladium carbon powder (specific surface area of carbon 950 m 2 / g, manufactured by Aldrich) was added. The reaction was allowed to proceed for 24 hours at room temperature under slightly pressurized hydrogen using a balloon. After the catalyst was filtered off, the reaction solution was analyzed by reverse phase HPLC to identify glycine. Yield 40%.

本発明の脱保護基方法は、ペプチド合成を始めとするバイオ産業での開発及び研究において有用である。   The deprotecting group method of the present invention is useful in development and research in the bio industry including peptide synthesis.

Claims (1)

9−フルオレニルメトキシカルボニル基で保護された基質を、比表面積1000m2/g以上の炭素粒子にパラジウムを固定したパラジウムカーボン触媒の存在下で、水素と湿式で接触させることを特徴とする9−フルオレニルメトキシカルボニル基の脱保護基方法。 A substrate protected by a 9-fluorenylmethoxycarbonyl group is contacted with hydrogen in the presence of a palladium carbon catalyst in which palladium is fixed to carbon particles having a specific surface area of 1000 m 2 / g or more. -Deprotection method for fluorenylmethoxycarbonyl group.
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JPH04154731A (en) * 1990-10-18 1992-05-27 Snow Brand Milk Prod Co Ltd Deprotection method
JPH06506680A (en) * 1991-04-25 1994-07-28 プロペプティートゥ Method for synthesizing peptides, novel amino acid derivatives used in said method, and methods for preparing the same
JP2004261751A (en) * 2003-03-03 2004-09-24 Ne Chemcat Corp Catalyst for hydrogenolysis and hydrogenolysis method using the same

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JPH024749A (en) * 1988-03-18 1990-01-09 Merck Patent Gmbh Amino acid derivative
JPH02292245A (en) * 1989-04-17 1990-12-03 Ciba Geigy Ag Protected amino acid and preparation thereof
JPH04154731A (en) * 1990-10-18 1992-05-27 Snow Brand Milk Prod Co Ltd Deprotection method
JPH06506680A (en) * 1991-04-25 1994-07-28 プロペプティートゥ Method for synthesizing peptides, novel amino acid derivatives used in said method, and methods for preparing the same
JP2004261751A (en) * 2003-03-03 2004-09-24 Ne Chemcat Corp Catalyst for hydrogenolysis and hydrogenolysis method using the same

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