JP2001064208A - Polyamine solid phase synthesis reaction method and solid phase reaction support - Google Patents
Polyamine solid phase synthesis reaction method and solid phase reaction supportInfo
- Publication number
- JP2001064208A JP2001064208A JP24036199A JP24036199A JP2001064208A JP 2001064208 A JP2001064208 A JP 2001064208A JP 24036199 A JP24036199 A JP 24036199A JP 24036199 A JP24036199 A JP 24036199A JP 2001064208 A JP2001064208 A JP 2001064208A
- Authority
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- Japan
- Prior art keywords
- solid phase
- polyamine
- amino group
- formula
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
(57)【要約】
【課題】 充填効率が高く、しかも切り出し操作等も容
易であって、生理活性機序の検討にとっても有用なくも
毒ＨＯ−４１６ｂの全合成への適用も可能とする、新し
いポリアミン固相合成反応方法とそのための固相反応担
体を提供する。
【解決手段】 第１級アミノ基を有するポリアミン類の
第１級アミノ基を次式（Ａ）
【化１】
（式中のＰＡはポリマー固相を示し、式中のベンゼン環
は許容される置換基を有していてもよい。）で表わされ
る固相反応担体に反応連結し、連結された前記第１級ア
ミノ基以外の少くとも一つのアミノ基を化学反応させ
る。PROBLEM TO BE SOLVED: To provide a high filling efficiency, easy cutting-out operation, etc., which is not useful for the study of a physiologically active mechanism, and is applicable to the total synthesis of a poison HO-416b. A new polyamine solid-phase synthesis reaction method and a solid-phase reaction support therefor are provided. SOLUTION: The primary amino group of the polyamine having a primary amino group is represented by the following formula (A): (Wherein PA in the formula represents a polymer solid phase, and the benzene ring in the formula may have an acceptable substituent.) At least one amino group other than the primary amino group is chemically reacted.
Description
【０００１】[0001]
【発明の属する技術分野】この出願の発明は、ポリアミ
ン固相合成反応方法と固相反応担体に関するものであ
る。さらに詳しくは、この出願の発明は、充填効率が高
く、高い極性を持つポリアミン類を、煩雑な精製操作を
必要とすることなく単離精製することをも可能とする新
しい固相反応担体の使用によるポリアミン固相合成反応
方法と、このための固相反応担体に関するものである。TECHNICAL FIELD The invention of this application relates to a polyamine solid phase synthesis reaction method and a solid phase reaction carrier. More specifically, the invention of this application relates to the use of a new solid-phase reaction carrier that enables polyamines having high packing efficiency and high polarity to be isolated and purified without requiring complicated purification operations. And a solid-phase reaction support for the method.
【０００２】[0002]
【従来の技術とその課題】従来より、固相合成法は、１
９６０年にマレーフィールドがその方法論を発表して以
来、ペプチドや核酸のような高分子化合物の合成に盛ん
に用いられてきている。そして近年になって、新規薬物
探索のために一度に数万種類の化合物を合成するコンビ
ナトリアルケミストリーの観点からも注目されているの
が固相合成法である。2. Description of the Related Art Conventionally, solid-phase synthesis has been carried out by one method.
Since Murrayfield published its methodology in 960, it has been actively used in the synthesis of macromolecular compounds such as peptides and nucleic acids. In recent years, the solid-phase synthesis method has attracted attention from the viewpoint of combinatorial chemistry in which tens of thousands of compounds are synthesized at once to search for new drugs.
【０００３】これまでにもこの固相合成についてはより
効率の高い固相の開発について様々な検討が加えられて
きており、数多くの固相反応担体が提案されてもいる。
しかしながら、従来の固相合成とそのための固相反応担
体についての数多くの提案にもかかわらず、アミノ基窒
素原子を連結する固相反応担体についてはいずれも一長
一短があった。たとえば固相からの切り出しに強い条件
が必要であったり、充填効率が低い等の問題があった。Various studies have been made on the development of a more efficient solid phase for the solid phase synthesis, and a number of solid phase reaction carriers have been proposed.
However, despite the many proposals on the conventional solid phase synthesis and the solid phase support therefor, all of the solid phase supports that link an amino group nitrogen atom have advantages and disadvantages. For example, there have been problems such as the need for strong conditions for cutting out from the solid phase and the low filling efficiency.
【０００４】この出願の発明者らは、従来その全合成が
極めて困難であったポリアミン類の一種としての次式
（Ｃ）[0004] The inventors of the present application disclose the following formula (C) as a kind of polyamines whose total synthesis has heretofore been extremely difficult.
【０００５】[0005]
【化５】 で表わされるくも毒ＨＯ−４１６ｂの全合成を可能とす
べく検討し、この全合成において固相合成反応を採用し
ようとしてきた。しかし、従来の固相合成のための担体
等の手段の適用は難しいのが実情であった。Embedded image Have been studied to enable the total synthesis of the spider venom HO-416b represented by the following formula, and have attempted to employ a solid-phase synthesis reaction in this total synthesis. However, it has been difficult to apply conventional means such as a carrier for solid phase synthesis.
【０００６】そこで、この出願の発明は、以上のとおり
の従来技術の問題点を解消し、充填効率が高く、しかも
切り出し操作等も容易であって、生理活性機序の検討に
とっても有用なくも毒ＨＯ−４１６ｂの全合成への適用
も可能とする。新しいポリアミン固相合成反応方法とそ
のための固相反応担体を提供することを課題としてい
る。Accordingly, the invention of this application solves the above-mentioned problems of the prior art, has a high filling efficiency, is easy to cut out, etc., and is not useful for studying the physiologically active mechanism. The application to the total synthesis of the poison HO-416b is also possible. It is an object of the present invention to provide a new polyamine solid-phase synthesis reaction method and a solid-phase reaction support therefor.
【０００７】[0007]
【課題を解決するための手段】この出願の発明は、上記
のとおりの課題を解決するものとして、第１には、第１
級アミノ基を有するポリアミン類の第１級アミノ基を次
式（Ａ）Means for Solving the Problems The invention of the present application aims at solving the problems as described above.
The primary amino group of polyamines having a secondary amino group is represented by the following formula (A)
【０００８】[0008]
【化６】 （式中のＰＡはポリマー固相を示し、式中のベンゼン環
は許容される置換基を有していてもよい。）で表わされ
る固相反応担体に反応連結し、連結された前記第１級ア
ミノ基以外の少くとも一つのアミノ基を化学反応させる
ことを特徴とするポリアミン固相合成反応方法を提供す
る。Embedded image (Wherein PA in the formula represents a polymer solid phase, and the benzene ring in the formula may have an acceptable substituent.) A polyamine solid phase synthesis reaction method characterized by chemically reacting at least one amino group other than a primary amino group.
【０００９】また、この出願の発明は、第２には、化学
反応の終了後に酸性条件下に固相反応担体から切り出す
前記ポリアミン固相合成反応方法を提供し、第３には、
ポリアミン類が次式（Ｂ）Further, the invention of this application provides, secondly, the above-mentioned polyamine solid phase synthesis reaction method for cleaving from a solid phase reaction support under acidic conditions after completion of a chemical reaction.
Polyamines having the following formula (B)
【００１０】[0010]
【化７】 （式中のＮｓは、２−ニトロベンゼンスルホニル基を示
す）で表わされるものであって、Ｎｓ基の脱保護を行
い、次式（Ｃ）Embedded image (Ns in the formula represents a 2-nitrobenzenesulfonyl group). The Ns group is deprotected, and the following formula (C)
【００１１】[0011]
【化８】 で表わされるくも毒ＨＯ−４１６ｂ化合物もしくはその
誘導体を合成する前記の固相合成反応方法を提供する。Embedded image The above-mentioned solid-phase synthesis reaction method for synthesizing a spider venom HO-416b compound represented by the following formula or a derivative thereof is provided.
【００１２】さらにこの出願は、第４には、次式（Ａ）Further, the present application is based on the following formula (A):
【００１３】[0013]
【化９】 （式中のＰＡはポリマー固相を示し、式中のベンゼン環
は許容される置換基を有していてもよい。）で表わされ
るポリアミン類の固相反応担体も提供する。Embedded image (Wherein PA in the formula represents a polymer solid phase, and the benzene ring in the formula may have an acceptable substituent).
【００１４】[0014]
【発明の実施の形態】この出願の発明は、上記のとおり
の特徴をもつものであるが、以下にその実施の形態につ
いて説明する。BEST MODE FOR CARRYING OUT THE INVENTION The invention of this application has the features as described above, and embodiments thereof will be described below.
【００１５】この出願の発明のポリアミン固相合成反応
方法では、前記のとおりの式（Ａ）で表わされる固相反
応担体を用いる。このものは、従来市販の１級アミンの
連結に用いられる固相担体よりも充填効率が高く、なお
かつ切り出し等の操作が容易であるという優れた特徴を
有している。なお、この発明の式（Ａ）における固相反
応担体は、前記のとおり、構造中のベンゼン環には、ア
ルキル基をはじめとする許容される置換基を有していて
もよく、また、ポリマー固相（ＰＡ）については、各種
ポリマーにより構成されていてよく、代表的にはポリス
チレンであるものが例示される。このポリスチレン固相
のものは、たとえば市販のMerrifield resinより製造す
ることができる。In the polyamine solid phase synthesis reaction method of the invention of the present application, the solid phase reaction carrier represented by the above formula (A) is used. This product has the excellent characteristics that the packing efficiency is higher than that of a solid phase carrier conventionally used for linking a commercially available primary amine, and that the operation such as cutting out is easy. As described above, the solid-phase reaction support in formula (A) of the present invention may have an allowable substituent such as an alkyl group on the benzene ring in the structure. The solid phase (PA) may be composed of various polymers, and a typical example is polystyrene. This polystyrene solid phase can be produced, for example, from a commercially available Merrifield resin.
【００１６】以上のこの発明の固相反応担体を用いての
ポリアミン固相合成反応方法では、第１級アミノ基、す
なわち−ＮＨ2 基を持つポリアミン類のこの第１級アミ
ノ基を前記の固相反応担体に反応連結し、連結されてい
ないアミノ基について所望の化学反応を行わせることに
なる。この場合の反応は各種のものでよく、窒素原子と
の結合の形成、窒素原子の置換等の広範な反応が考慮さ
れる。当然のこととして、この反応には、通常の意味で
示される保護基による窒素原子の保護や、保護基の脱離
の反応も含まれる。In the above-described method for solid-phase synthesis of polyamine using the solid-phase reaction carrier of the present invention, the primary amino group, that is, the primary amino group of polyamines having an -NH 2 group is The reaction is connected to the phase reaction carrier, and the desired chemical reaction is performed on the unlinked amino group. The reaction in this case may be of various types, and a wide range of reactions such as formation of a bond with a nitrogen atom and substitution of a nitrogen atom are considered. As a matter of course, this reaction includes protection of a nitrogen atom by a protecting group having the usual meaning, and reaction of elimination of the protecting group.
【００１７】また、対象とする原料のポリアミン類、そ
して目的とする反応生成物も各種のものであってよい。
原料ポリアミンとしては、前記のとおりの第１級アミノ
基（−ＮＨ2 ）を持つ、さらに他にアミノ基を分子構造
中に有しているものとして特定される。なかでも第１級
アミノ基（−ＮＨ2 ）が、さらにはこの第１級アミノ基
（−ＮＨ2 ）と他のアミノ基とがともに、脂肪族炭素
（鎖）に結合しているポリアミン類が好適なものとして
例示される。The target raw materials, such as polyamines, and the desired reaction products may be of various types.
The raw material polyamine is specified as having a primary amino group (—NH 2 ) as described above and further having an amino group in the molecular structure. Among them a primary amino group (-NH 2), further both the first primary amino group (-NH 2) with other amino groups, polyamines bound to aliphatic carbon (chain) of It is exemplified as a suitable one.
【００１８】反応終了後のこの発明の固相反応担体から
の切り出しは、たとえば酸性条件下で容易に行うことが
でき、溶媒を留去するのみで純粋な反応生成化合物を取
得することもでき、煩雑な精製操作をほとんど必要とし
ていない。Cleavage from the solid-phase reaction support of the present invention after the completion of the reaction can be easily performed, for example, under acidic conditions, and a pure reaction product can be obtained only by distilling off the solvent. Almost no complicated purification operation is required.
【００１９】以上のとおりのこの発明の固相合成反応方
法により、たとえば後述の実施例にも示したように、従
来その全合成が難しかったくも毒ＨＯ−４１６ｂ化合
物、もしくはその誘導体の効率的な全工程も可能とな
る。According to the solid-phase synthesis reaction method of the present invention as described above, for example, as shown in the Examples described later, the total synthesis of toxic HO-416b compound or its derivative can be efficiently carried out. A process is also possible.
【００２０】そこで以下に実施例を示し、さらに詳しく
この出願の発明について説明する。Therefore, the present invention will be described below in more detail with reference to Examples.
【００２１】[0021]
【実施例】（実施例１）次の反応式；EXAMPLES (Example 1) The following reaction formula:
【００２２】[0022]
【化１０】 に従って、固相反応担体としての４−（クロルジフェニ
ルメチル）フェノキシメチル−ポリスチレンを製造し
た。Embedded image Was used to produce 4- (chlorodiphenylmethyl) phenoxymethyl-polystyrene as a solid-phase reaction carrier.
【００２３】すなわち、１．４０ｇ（１．６８ｍｍｏ
ｌ）のMerrifield Resinと、４．６４ｇ（１６．８ｍｍ
ｏｌ）のＰ−ヒドロキシトリチルアルコールの３０ｍｌ
ＤＭＦの懸濁液に、室温およびアルゴン雰囲気下に１
１．６ｇ（８４．０ｍｍｏｌ）の炭酸カリウムを添加
し、６０℃の温度で２０時間加熱した。その後室温に冷
却した。That is, 1.40 g (1.68 mmo)
1) Merrifield Resin and 4.64 g (16.8 mm)
ol) of P-hydroxytrityl alcohol
Add 1 ml of DMF to the suspension at room temperature and under argon atmosphere.
1.6 g (84.0 mmol) of potassium carbonate was added and heated at a temperature of 60 ° C. for 20 hours. Then, it cooled to room temperature.
【００２４】生成物を濾別し、Ｈ2 Ｏ：ＴＨＦ（１：
９）およびＥｔ2 Ｏにより洗浄し、次いで真空乾燥して
１．５４ｇの樹脂生成物を得た。この樹脂生成物のＣＨ
2 Ｃｌ2 懸濁液に、室温およびアルゴン雰囲気下でＳＯ
Ｃｌ2 を添加した。３０分間攪拌した。溶媒を蒸発除去
した後に、真空乾燥して、１．５４ｇの４−（クロルジ
フェニルメチル）フェノキシメチル−ポリスチレンを得
た。 （実施例２）次の反応式に従って、固相合成による脱保
護基反応を行った。The product is filtered off and H 2 O: THF (1:
Washed with 9) and Et 2 O, then dried in vacuo to give 1.54 g of resin product. CH of this resin product
The 2 Cl 2 suspension was treated with SO 2 at room temperature and under argon atmosphere.
Cl 2 was added. Stir for 30 minutes. After the solvent was removed by evaporation, the residue was dried under vacuum to obtain 1.54 g of 4- (chlorodiphenylmethyl) phenoxymethyl-polystyrene. (Example 2) A deprotection group reaction by solid-phase synthesis was performed according to the following reaction formula.
【００２５】[0025]
【化１１】 すなわち、まず、次式Embedded image That is, first,
【００２６】[0026]
【化１２】 で表わされるＮｓ（２−ニトロベンゼンスルホニル）基
により保護された、６５ｍｇ（０．０６８ｍｍｏｌ）の
ＨＯ−４１６ｂ化合物（１３）を、２．５ｍｌのＣＨ2
Ｃｌ2 溶媒中において、０．１４１ｍｌ（０．８２８ｍ
ｍｏｌ）のｉＰｒ 2 ＮＥｔの存在下に、実施例により製
造した固相反応担体と室温にて反応させた。Embedded imageNs (2-nitrobenzenesulfonyl) group represented by
65 mg (0.068 mmol) protected by
HO-416b compound (13) was added to 2.5 ml of CHTwo
ClTwo0.141 ml (0.828 m
mol) of iPr TwoMade according to the examples in the presence of NEt
The reaction was performed at room temperature with the produced solid phase reaction support.
【００２７】４８時間振とう後、０．１ｍｌのＭｅＯＨ
を添加し、濾別した後に、固相分をＭｅＯＨ：ＣＨ2 Ｃ
ｌ2 （１：９）、Ｈ2 Ｏ：ＭｅＯＨ：ＣＨ2 Ｃｌ
2 （１：１：８）、並びにＣＨ2 Ｃｌ2 により洗浄し、
その後真空乾燥した。以上のようにして、前記化合物
（１３）をこの固相反応担体に連結担持させた。After shaking for 48 hours, 0.1 ml of MeOH
Was added and filtered, and then the solid phase was separated from MeOH: CH 2 C
l 2 (1: 9), H 2 O: MeOH: CH 2 Cl
2 (1: 1: 8), and washed with CH 2 Cl 2 ,
Then, it was vacuum dried. As described above, the compound (13) was connected and supported on the solid-phase reaction support.
【００２８】この担持樹脂の１．５ｍｌ ＤＭＦ懸濁液
に、０．１４０ｍｌ（２．００ｍｍｏｌ）のメルカプト
エタノールおよび０．３０ｍｌ（２．００ｍｍｏｌ）の
ＤＢＵを、室温およびアルゴン雰囲気下に添加した。To a 1.5 ml DMF suspension of this supported resin, 0.140 ml (2.00 mmol) of mercaptoethanol and 0.30 ml (2.00 mmol) of DBU were added at room temperature and under an argon atmosphere.
【００２９】２６時間振とう後、濾別し、Ｈ2 Ｏ：ＴＨ
Ｆ（１：９）、ＭｅＯＨ：ＣＨ2 Ｃｌ2 （１：９）、並
びにＣＨ2 Ｃｌ2 により洗浄し、真空乾燥した。これに
よりＮｓ保護基の脱離を行った。After shaking for 26 hours, the mixture was filtered off, and H 2 O: TH
Washed with F (1: 9), MeOH: CH 2 Cl 2 (1: 9), and CH 2 Cl 2 and dried in vacuo. Thereby, the Ns protecting group was eliminated.
【００３０】次に、樹脂固相分の２．５ｍｌ ＣＨ2 Ｃ
ｌ2 混合物に、２５μｌ（０．３２４ｍｍｏｌ）のＴＦ
Ａを室温において添加した。５分間振とう後、濾別し、
ＭｅＯＨ：ＣＨ2 Ｃｌ2 （１：９）により洗浄した。Next, 2.5 ml of the resin solid phase CH 2 C
to l 2 mixture, TF of 25 [mu] l (0.324 mmol)
A was added at room temperature. After shaking for 5 minutes, filter
Washed with MeOH: CH 2 Cl 2 (1: 9).
【００３１】このような酸性条件下の切り出し操作をさ
らに３回繰り返した。洗浄後の液を一緒にして蒸発処理
し、真空乾燥して、くも毒ＨＯ−４１６ｂ（２５．５ｍ
ｇ、６８％）をＴＦＡ塩として得た。The cutting operation under such acidic conditions was repeated three more times. The liquids after washing are combined, evaporated and dried under vacuum to obtain a spider poison HO-416b (25.5 m
g, 68%) as a TFA salt.
【００３２】また、回収された樹脂固相担体はＳＯＣｌ
2 ：ＣＨ2 Ｃｌ2 （１：９）で処理することにより再利
用された。以上のことから、次のことが結論づけられ
る。Further, the recovered resin solid phase carrier is SOCl
2 : Recycled by treatment with CH 2 Cl 2 (1: 9). From the above, the following can be concluded.
【００３３】充填効率の高い、新しい固相を開発した。
ニトロベンゼンスルホンアミドの脱保護をその固相上で
行い、切り出すことによりポリアミンを得た。高い極性
をもつポリアミンを、煩雑な精製操作をすることなく、
溶媒を留去するのみで単離できたことは画期的である。 （実施例３）実施例２において用いたＮｓ基により保護
されたＨＯ−４１６ｂ化合物（１３）について、次の反
応式に従って合成した。A new solid phase with high packing efficiency has been developed.
Deprotection of nitrobenzenesulfonamide was performed on the solid phase, and a polyamine was obtained by cutting out. Polyamines with high polarity can be produced without complicated purification operations.
It is epoch-making that isolation was possible only by distilling off the solvent. Example 3 The HO-416b compound (13) protected by the Ns group used in Example 2 was synthesized according to the following reaction formula.
【００３４】[0034]
【化１３】 反応条件（ａ）〜（ｉ）は次のとおりである。Embedded image Reaction conditions (a) to (i) are as follows.
【００３５】[0035]
【表１】 以上の合成反応においては、たとえば化合物（９）と化
合物（１１）と反応収率が９４％であるように、Ｎｓ保
護基の採用によって極めて高い選択性で目的とするＮｓ
保護ＨＯ−４１６ｂ化合物（１３）が得られている。[Table 1] In the above synthesis reaction, the desired Ns can be obtained with extremely high selectivity by employing an Ns protecting group so that the reaction yield of the compound (9) and the compound (11) is 94%, for example.
The protected HO-416b compound (13) has been obtained.
【００３６】以上のことから次のことが確認された。 １）通常は困難であることが知られている、ジアミンの
片方のみの選択的保護を、ニトロベンゼンスルホンアミ
ド保護基により達成した。その保護されたジアミンを原
料として用いることにより、効率的にＨＯ−４１６ｂ化
合物の全合成を終了できた。From the above, the following was confirmed. 1) Selective protection of only one of the diamines, which is usually known to be difficult, was achieved with a nitrobenzenesulfonamide protecting group. By using the protected diamine as a raw material, the total synthesis of the HO-416b compound could be efficiently completed.
【００３７】２）すべての炭素−窒素結合を、スルホン
アミドとハライドとのアルキル化反応により構築した。
これらはスケールアップが可能であるばかりでなく、容
易に入手可能な種々のハライドを用いることにより多様
な化合物を合成可能である。2) All carbon-nitrogen bonds were established by the alkylation reaction of sulfonamides with halides.
Not only can these be scaled up, but also various compounds can be synthesized by using various readily available halides.
【００３８】[0038]
【発明の効果】以上詳しく説明したとおり、この出願の
発明によって、充填効率が高く、しかも切り出し操作等
も容易であって、生理活性機序の検討にとっても有用な
くも毒ＨＯ−４１６ｂの全合成への適用も可能とされ
る、新しいポリアミン固相合成反応方法とそのための固
相反応担体が提供される。As described above in detail, according to the invention of this application, the filling efficiency is high, the cutting operation is easy, and the total synthesis of the poison HO-416b is not useful for studying the physiologically active mechanism. The present invention provides a novel method for solid-phase synthesis reaction of polyamines and a solid-phase reaction carrier therefor, which can be applied to a polyamine.
Claims (4)
第１級アミノ基を次式（Ａ） 【化１】 （式中のＰＡはポリマー固相を示し、式中のベンゼン環
は許容される置換基を有していてもよい。）で表わされ
る固相反応担体に反応連結し、連結された前記第１級ア
ミノ基以外の少くとも一つのアミノ基を化学反応させる
ことを特徴とするポリアミン固相合成反応方法。1. The primary amino group of a polyamine having a primary amino group is represented by the following formula (A): (Wherein PA in the formula represents a polymer solid phase, and the benzene ring in the formula may have an acceptable substituent.) A polyamine solid phase synthesis reaction method comprising chemically reacting at least one amino group other than a primary amino group.
応担体から切り出す請求項１のポリアミン固相合成反応
方法。2. A polyamine solid phase synthesis reaction method according to claim 1, wherein the polyamine is cleaved from the solid phase reaction support under acidic conditions after completion of the chemical reaction.
す）で表わされるものであって、Ｎｓを保護基として用
い、次式（Ｃ） 【化３】 で表わされるくも毒ＨＯ−４１６ｂ化合物もしくはその
誘導体を合成する請求項１または２の固相合成反応方
法。3. The polyamine represented by the following formula (B): (Ns in the formula represents a 2-nitrobenzenesulfonyl group), wherein Ns is used as a protecting group, and the following formula (C) is used. The solid phase synthesis reaction method according to claim 1 or 2, wherein the compound represented by the formula: HO-416b or a derivative thereof is synthesized.
は許容される置換基を有していてもよい。）で表わされ
るポリアミン類の固相反応担体。4. The following formula (A): (PA in the formula represents a polymer solid phase, and the benzene ring in the formula may have an allowable substituent.)
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