JPS61277690A - Pyridoxamine type pyridinophane compound and production thereof - Google Patents
Pyridoxamine type pyridinophane compound and production thereofInfo
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- JPS61277690A JPS61277690A JP12075885A JP12075885A JPS61277690A JP S61277690 A JPS61277690 A JP S61277690A JP 12075885 A JP12075885 A JP 12075885A JP 12075885 A JP12075885 A JP 12075885A JP S61277690 A JPS61277690 A JP S61277690A
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- compound
- pyridinophane
- pyridoxamine
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Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、ピリドキサミン型ピリジノファン化合物およ
びその製造法に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a pyridoxamine-type pyridinophane compound and a method for producing the same.
生体内では不斉触媒としての酵素の働きで、多数のキラ
ルな化合物がアキラルな前駆体から合成されている。酵
素によっては反応の進行を低分子の補酵素が受持ってい
る場合もあるが、不斉な反応場を提供して生成物を光学
活性にするのはすべて酵素蛋白の役割である。このよう
な酵素機能に類似した働きができる低分子化合物を設計
、調製して有用物質の不斉合成に利用することができれ
ば、酵素に特有な不安定性、至適反応条件の狭さ、厳格
な基質特異性などから開放された酵素能化学素子として
、極めて利用価値が高いものと考えられる。In living organisms, many chiral compounds are synthesized from achiral precursors by the action of enzymes as asymmetric catalysts. Depending on the enzyme, the progress of the reaction may be carried out by a low-molecular coenzyme, but in all cases it is the role of the enzyme protein to provide an asymmetric reaction field and make the product optically active. If it were possible to design and prepare low-molecular-weight compounds that can perform functions similar to those of enzymes and use them for the asymmetric synthesis of useful substances, it would be possible to overcome the inherent instability of enzymes, the narrowness of optimal reaction conditions, and the strict It is considered to have extremely high utility value as an enzymatic chemical element free from substrate specificity.
ところで、ピリドキサミンは、金属イオンの存在下、α
−ケト酸と処理すると、ピリドキサミンからケト酸への
アミノ基転移反応がおこり、ピリドキサールとα−アミ
ノ酸を生ずることが知られている。この反応はアミノ酸
製造上注目すべきものであるが、生ずるアミノ酸がラセ
ミ体であるため、このままでは一般に必要とされている
光学活性アミノ酸の製造法とはなりえない。By the way, pyridoxamine has α
- It is known that when treated with a keto acid, a transamination reaction of pyridoxamine to the keto acid occurs, producing pyridoxal and an α-amino acid. Although this reaction is noteworthy in the production of amino acids, since the amino acids produced are racemic, it cannot be used as is as a method for producing generally needed optically active amino acids.
そこで本発明者は先に、このアミノ基転移反応を基盤と
して直接光学活性アミノ酸を与えることができる化合物
について研究を行い、ピリドキサミンの基本骨格(ピリ
ジン環、アミノメチル基、フェノール性水酸基)を組込
んだ光学活性ピリドキサミン型ピリジノファン化合物(
1)を合成し、該化合物が上記目的を達成し得ることを
見出した(特公昭55−42077号公報参照)。Therefore, the present inventors first conducted research on compounds that can directly provide optically active amino acids based on this transamination reaction, and incorporated the basic skeleton of pyridoxamine (pyridine ring, aminomethyl group, phenolic hydroxyl group). optically active pyridoxamine-type pyridinophane compounds (
1) and found that the compound could achieve the above object (see Japanese Patent Publication No. 55-42077).
本発明者らは、上記化合物(1)を用いたアミノ基転移
反応の光学収率をさらに向上させるために鋭意研究を行
った。反応機構の解析の結果、化合物(1)のS原子と
その周辺による立体障害をさらに大きくすることにより
生成物の光学収率を高めることができるという結論を得
た。そこで化合物(1)のS原子を選択的にスルホンへ
酸化した化合物(5)を合成し、該化合物がアミノ基転
移反応の光学収率をさらに向上し得ることを見出し、本
発明を完成するに至った。The present inventors conducted extensive research in order to further improve the optical yield of the transamination reaction using the above compound (1). As a result of analysis of the reaction mechanism, it was concluded that the optical yield of the product could be increased by further increasing the steric hindrance caused by the S atom of compound (1) and its surroundings. Therefore, we synthesized compound (5) in which the S atom of compound (1) was selectively oxidized to sulfone, and discovered that this compound could further improve the optical yield of transamination reaction, and completed the present invention. It's arrived.
本発明の目的は、新規なピリドキサミン型ピリジノファ
ン化合物およびその製造法を提供することである。An object of the present invention is to provide a novel pyridoxamine-type pyridinophane compound and a method for producing the same.
本発明は、下記の一船式で表されるピリドキサミン型ピ
リジノファン化合物である。The present invention is a pyridoxamine-type pyridinophane compound represented by the following formula.
CH2NR’R2
式中、R’ 1R2およびR3は、独立に、水素原子ま
たはアセチル基を示す。上記化合物は、たとえば式(1
)
CH2N H2
で表される前記化合物(1)をアセチル化して、式(2
)
%式%)
で表される化合物(2)を得、これを酸化剤で処理した
後、必要により脱アセチル化することにより合成するこ
とができる。CH2NR'R2 In the formula, R' 1R2 and R3 independently represent a hydrogen atom or an acetyl group. The above compound is, for example, a compound of the formula (1
) The compound (1) represented by CH2N H2 is acetylated to form the formula (2
) It can be synthesized by obtaining a compound (2) represented by the following formula, treating it with an oxidizing agent, and then deacetylating it if necessary.
上記化合物の具体例としては、たとえば次のものを挙げ
ることができる。Specific examples of the above compounds include the following.
014−アセトキシ−15(ジアセチルアミノ)メチル
−2,8−ジチアC9’] (2,5)ピリジノファ
ンs、s、s’、s’−テトラオキシド[化合物(3)
コ
014−ヒドロキシ−15(アセチルアミノ)メチル−
2,゛8−ジチア[9m (2,5)ピリジノファン
s、s、s’、s’−テトラオキシド[化合物(4)]
014−ヒドロキシ、−15−アミノメチル−2゜8−
ジチア[9] (2,5)ピリジノファンs、s、s
’、s’−テトラオキシド[化合物(5)]
本発明の化合物を合成するための出発物質(1)は、た
とえば特公昭55−42077号記載の方法により製造
することができる。014-acetoxy-15(diacetylamino)methyl-2,8-dithiaC9'] (2,5) Pyridinophane s, s, s', s'-tetraoxide [Compound (3)
co014-hydroxy-15(acetylamino)methyl-
2,゛8-dithia[9m (2,5)pyridinophane s, s, s', s'-tetraoxide [compound (4)] 014-hydroxy, -15-aminomethyl-2゜8-
Dithia [9] (2,5) pyridinophane s, s, s
',s'-Tetraoxide [Compound (5)] The starting material (1) for synthesizing the compound of the present invention can be produced, for example, by the method described in Japanese Patent Publication No. 55-42077.
化合物(1,)を、無水酢酸/ピリジン等のアセチル化
剤で水酸基およびアミノ基をアセチル化し、化合物(2
)を得る。このアセチル体(2)を、酸化剤で処理して
、ジスルホン化合物(3)を得る。The hydroxyl group and amino group of compound (1,) are acetylated with an acetylating agent such as acetic anhydride/pyridine to form compound (2).
). This acetyl compound (2) is treated with an oxidizing agent to obtain a disulfone compound (3).
酸化剤としては、過酸化水素、有機過酸、たとえば、過
安息香酸、m−クロロ過安息香酸、過酢酸、過ギ酸、ペ
ルオキソ酸、たとえばペルオキソ硝酸、ペルオキソ(−
)リン酸、ペルオキソニリン酸、ペルオキソ(−)硫酸
、ベルオキソニ硫酸、等を使用することができる。Oxidizing agents include hydrogen peroxide, organic peracids such as perbenzoic acid, m-chloroperbenzoic acid, peracetic acid, performic acid, peroxoacids such as peroxonitric acid, peroxo(-
) phosphoric acid, peroxoniphosphoric acid, peroxo(-)sulfuric acid, peroxonisulfuric acid, etc. can be used.
過酸化水素を用いるばあいには、たとえばジオキサン/
水混合溶媒等にアセチル体(2)を溶解し、少量のタン
グステン酸ナトリウムおよび酢酸等の触媒の存在下、過
酸化水素水溶液を滴下し反応させる。反応温度は60℃
〜90℃、反応時間は3時間〜8時間程度が適当である
。When using hydrogen peroxide, for example dioxane/
The acetyl compound (2) is dissolved in a water mixed solvent or the like, and an aqueous hydrogen peroxide solution is added dropwise to react in the presence of a small amount of a catalyst such as sodium tungstate and acetic acid. Reaction temperature is 60℃
A temperature of ~90°C and a reaction time of about 3 to 8 hours are appropriate.
またm−クロロ過安息香酸を用いるばあいには、たとえ
ばクロロホルム、エタノール等にアセチル体(2)を溶
解し、m−クロロ過安息香酸の同溶媒溶液を滴下し反応
させる。0℃〜20℃でm−クロロ過安息香酸を滴下し
、滴下終了後、20℃〜30℃で10〜30時間程度、
攪拌すればよい。When m-chloroperbenzoic acid is used, the acetyl compound (2) is dissolved in, for example, chloroform or ethanol, and a solution of m-chloroperbenzoic acid in the same solvent is added dropwise to react. m-chloroperbenzoic acid was added dropwise at 0°C to 20°C, and after the dropwise addition was completed, the mixture was heated at 20°C to 30°C for about 10 to 30 hours.
Just stir.
過酸化水素を用いるとヒドロキシ−モノアセチルアミノ
体(4)を、m−クロロ過安息香酸/クロロホルムを用
いるとペンタオキシド体(6)[14−アセトキシ−1
5(ジアセチルアミノ)メチル−2,8ニジチア[9]
(2,5)ピリジノファンN、S、S、S’、S’
−ペンタオキシド]を、それぞれ副生ずる。When using hydrogen peroxide, the hydroxy-monoacetylamino compound (4) is obtained, and when m-chloroperbenzoic acid/chloroform is used, the pentaoxide compound (6) [14-acetoxy-1
5(Diacetylamino)methyl-2,8 Nidithia [9]
(2,5) Pyridinophane N, S, S, S', S'
-pentoxide] are produced as by-products.
かくして得られた化合物(3)または(4)、または化
合物(3)と(4)の混合物を、たとえば塩酸等で処理
すると脱アセチル体(5)が得られる。またペンタオキ
シド体(6)を同様に脱アセチル化すると化合物(7)
[3,4−ヒドロキシ−15−アミノメチル−2,8−
ジチア[9](2,5)ピリジノファンN、S、S、S
’。When the thus obtained compound (3) or (4) or a mixture of compounds (3) and (4) is treated with, for example, hydrochloric acid, the deacetylated compound (5) is obtained. Similarly, deacetylation of pentaoxide compound (6) yields compound (7).
[3,4-hydroxy-15-aminomethyl-2,8-
Dithia[9](2,5)pyridinophane N, S, S, S
'.
S′−ペンタオキシド]を得る。S'-pentaoxide] is obtained.
本発明方法により合成される上記化合物(2)、(3つ
、(4)、(5)、(6)および(7)は新規化合物で
ある。The above compounds (2), (3), (4), (5), (6) and (7) synthesized by the method of the present invention are new compounds.
本発明の新規なピリドキサミン型ピリジノファン化合物
(5)は、光学活性アミノ酸の合成試薬として重要であ
る。The novel pyridoxamine-type pyridinophane compound (5) of the present invention is important as a reagent for the synthesis of optically active amino acids.
すなわち、たとえば左旋性または右旋性のピリドキサミ
ン型ピリジノファン化合物(5)を、乾燥メタノールま
たはアセトニトリル中、α−ケト酸ナトリウム塩および
過塩素酸亜鉛と室温で反応させ、次いで酸加水分解後、
有機溶媒抽出およびイオン交換クロマトグラフィーによ
り生成物を単離することにより、光学活性アミノ酸を収
率よく得ることができる。また、左旋性のピリドキサミ
ン型ピリジノファン化合物(5)を用いると右旋性アミ
ノ酸が、右旋性ピリドキサミン型ピリジノファン化合物
(5)を用いると左旋性アミノ酸が優勢に生ずる。この
際、光学活性なピリドキサール型ピリジノファン化合物
(8)[14−ヒドロキシ−15−ホルミル−2,8−
ジチア[9コ(2,5)ピリジノファンs、s、s’、
s’−テトラオキシトコが生じ、これは好収率で回収す
ることができ、再びピリドキサミン型ピリジノファン化
合物(5)の製造に用いることができる。That is, for example, a levorotatory or dextrorotatory pyridoxamine type pyridinophane compound (5) is reacted with α-keto acid sodium salt and zinc perchlorate in dry methanol or acetonitrile at room temperature, and then after acid hydrolysis,
Optically active amino acids can be obtained in good yield by isolating the product by organic solvent extraction and ion exchange chromatography. Furthermore, when the levorotatory pyridoxamine-type pyridinophane compound (5) is used, dextro-rotatory amino acids are predominantly produced, and when the dextro-rotatory pyridoxamine-type pyridinophane compound (5) is used, levorotatory amino acids are predominantly produced. At this time, an optically active pyridoxal-type pyridinophane compound (8) [14-hydroxy-15-formyl-2,8-
Dithia [9(2,5)pyridinophanes, s, s',
s'-tetraoxytoco is produced, which can be recovered in good yield and used again in the production of pyridoxamine-type pyridinophane compound (5).
以下に本発明を実施例により詳細に説明する。The present invention will be explained in detail below using examples.
実施例1
(S)−(−)−15−アミノメチル−14−ヒドロキ
シ−2,8−ジチア[9] (2,5)ピリジノファ
ン(1)2.53gをピリジン25m1と無水酢酸25
m1に溶解し、攪拌しながら100℃に16時間加熱す
る。減圧下70℃で出来るだけ濃縮し氷水を加える。酢
酸エチルで抽出し炭酸水素ナトリウム水溶液、水で洗浄
し乾燥(無水硫酸マグネシウム)後、濃縮する。残渣を
シリカゲルのクロマトカラム(溶出液クロロホルム−メ
タノール100:1)で精製し、(S)−(−)−14
−アセトキシ−15−(ジアセチルアミノ)メチル−2
,8−ジチア[9] (2,5)ピリジノファン[化合
物(S)−(−)−(2)]を得る。Example 1 2.53 g of (S)-(-)-15-aminomethyl-14-hydroxy-2,8-dithia [9] (2,5) pyridinophane (1) was mixed with 25 ml of pyridine and 25 ml of acetic anhydride.
m1 and heated to 100° C. for 16 hours with stirring. Concentrate as much as possible under reduced pressure at 70°C and add ice water. Extract with ethyl acetate, wash with aqueous sodium bicarbonate solution and water, dry (anhydrous magnesium sulfate), and concentrate. The residue was purified with a silica gel chromatography column (eluent: chloroform-methanol 100:1) to give (S)-(-)-14
-acetoxy-15-(diacetylamino)methyl-2
, 8-dithia[9] (2,5)pyridinophane [compound (S)-(-)-(2)] is obtained.
〔化合物(S)−(−)−(2)の性質〕mp 14
’? −8℃ 収量3.18g(87%)[α コ
o” 42.6 ° (C0,384、
CHCt、)UVma、(C)IC13) 289n
m (C4,OX 10’)IR1780(エステル)
、1710.1690cm−’ (7ミド)
実施例2
化合物(S)−(−)−(2)3.08gをジオキサン
60mlと水30mlの混液に溶解し、タングステン酸
ナトリウム2水和物を約5 mgと酢酸的50μlを加
えて60〜65℃に加熱し、30%過酸化水素水溶液3
.8mlを攪拌しながら30分で滴下した後80−85
℃に6時間加熱する。冷却後、5%亜硫酸水素す) I
Jウム水溶液を加えて過剰の過酸化水素を分解し、クロ
ロホルムで抽出する。乾燥(無水硫酸マグネシウム)後
濃縮し、シリカゲルカラムクロマトを行う。クロロホル
ム−メタノール(50:1)で(S)−(−)−14−
アセドキシー15−(ジアセチルアミノ)メチル−2,
8−ジチア[9] (2,5)ピリジノファンs、s
、s’、s’−テトラオキシド[化合物(S)−(−)
−(3)]を溶出させた後、クロロホルム−メタノー
ル(10:1)で(S)−(−)−15−(アセチルア
ミノ)メチル−14−ヒドロキシ−2,8−ジチア[9
] (2,5)ピリジノファンs、s、s’、s’−
テトラオキシド、[化合物(S)−(−)−(4)コを
溶出させる。[Properties of compound (S)-(-)-(2)] mp 14
'? -8℃ Yield 3.18g (87%) [α
o" 42.6 ° (C0,384,
CHCt, )UVma, (C)IC13) 289n
m (C4,OX 10')IR1780 (ester)
, 1710.1690 cm-' (7 mido) Example 2 3.08 g of compound (S)-(-)-(2) was dissolved in a mixture of 60 ml of dioxane and 30 ml of water, and about 5 ml of sodium tungstate dihydrate was dissolved. Add 50 μl of acetic acid and heat to 60-65°C, and add 30% hydrogen peroxide aqueous solution 3.
.. 80-85 after dropping 8ml over 30 minutes while stirring
Heat to ℃ for 6 hours. After cooling, add 5% hydrogen sulfite) I
Excess hydrogen peroxide is decomposed by adding an aqueous solution of hydrogen peroxide, and extracted with chloroform. After drying (anhydrous magnesium sulfate), concentrate and perform silica gel column chromatography. (S)-(-)-14- with chloroform-methanol (50:1)
Acedoxy-15-(diacetylamino)methyl-2,
8-dithia[9] (2,5)pyridinophane s, s
, s', s'-tetraoxide [compound (S)-(-)
-(3)], then (S)-(-)-15-(acetylamino)methyl-14-hydroxy-2,8-dithia[9
] (2,5) pyridinophane s, s, s', s'-
Tetraoxide, [compound (S)-(-)-(4)] is eluted.
〔化合物(S)−(−)−(3)の性質〕mp 20
4−5℃ 収量1.19.g (33%)[α コ 、
” −78° (C0,363、CHCl 3
)UVmax (CHCl3) 282nm Cε
4.2 X 103)1、R1790(エステル)、1
710.1690cm−’ (アミド)
〔化合物(S)−(−)−(4)の性質〕mp 26
6−7℃(分解) 収量0.89 g(30%)
[α]。”−168° (C0,321、ピリジン)I
R3400(アミド)、
1650C[O−’ (アミド)
実施例3
エタノール10m1、水5mlと濃塩酸5mlの混合液
に化合物(S)−(−) −(3)1.15gを加えて
3時間還流する。活性炭処理をして濃縮し、残渣にエタ
ノールを加えると15−アミノメチル−14−ヒドロキ
シ−2,8−ジチア[9コ(2゜5)ピリジノファンs
、s、s’、s’−テトラオキシド[化合物(S)−(
−)−(5)]のモノ塩酸塩が析出する。[Properties of compound (S)-(-)-(3)] mp 20
4-5°C Yield 1.19. g (33%) [α co,
” -78° (C0,363, CHCl3
)UVmax (CHCl3) 282nm Cε
4.2 X 103) 1, R1790 (ester), 1
710.1690cm-' (amide) [Properties of compound (S)-(-)-(4)] mp 26
6-7°C (decomposition) Yield 0.89 g (30%) [α]. ”-168° (C0,321, pyridine) I
R3400 (amide), 1650C[O-' (amide) Example 3 1.15 g of compound (S)-(-)-(3) was added to a mixture of 10 ml of ethanol, 5 ml of water, and 5 ml of concentrated hydrochloric acid, and refluxed for 3 hours. do. After treatment with activated carbon and concentration, and adding ethanol to the residue, 15-aminomethyl-14-hydroxy-2,8-dithia[9(2°5)pyridinophanes]
, s, s', s'-tetraoxide [compound (S)-(
-)-(5)] monohydrochloride is precipitated.
〔化合物(S)−(−)−(5)のモノ塩酸塩の性質〕 mp>280℃ 収量0.80g(74%)。[Properties of monohydrochloride of compound (S)-(-)-(5)] mp>280°C Yield 0.80g (74%).
[α]。2’−317° (Co、 293、H2O)
UV’+aax (H2O) 333nm (E
3.7 X 10’)、301nm(C4,lX10
3)、2’55nm(C3,7x103)
化合物(S) −(−) −(5)のモノ塩酸塩0、7
1 ? gを水15m1に溶解し、炭酸水素ナトリウム
0.164 gを固体のまま加えて30分室温で攪拌し
、化合物(S)−(−)−(5)の゛沈澱を濾別する。[α]. 2'-317° (Co, 293, H2O)
UV'+aax (H2O) 333nm (E
3.7 X 10'), 301 nm (C4, lX10
3), 2'55nm (C3,7x103) Monohydrochloride of compound (S) -(-)-(5) 0,7
1? g was dissolved in 15 ml of water, 0.164 g of sodium hydrogen carbonate was added as a solid, stirred at room temperature for 30 minutes, and the precipitate of compound (S)-(-)-(5) was filtered off.
〔化合物(S> −(−)−(5)の性質〕mp196
−9℃分解 収量0.613 g(96%)
[α]、+9−352° (C0,241、ピリジン)
UV、、、<ジオキサン)300nm(C2,9x実施
例4
エタノール10m1.水5mlと濃塩酸5ml中に化合
物(S)−(−)−(4)0.85gを加えて3時間還
流する。以下実施例3と同様に処理を行い、化合物(]
−(−) −(5)を得る。収量0.71g(85%)
実施例5
化合物(1)のラセミ体10. OOgをピリジン10
0mlと無水酢酸100mlの混液に溶解し、実施例1
と同様に処理を行い、化合物(2)のラセミ体を定量的
に得る。[Properties of compound (S> -(-)-(5))] mp196
-9℃ decomposition Yield 0.613 g (96%) [α], +9-352° (C0,241, pyridine)
UV, <Dioxane) 300 nm (C2,9x Example 4 10 ml of ethanol. Add 0.85 g of compound (S)-(-)-(4) to 5 ml of water and 5 ml of concentrated hydrochloric acid and reflux for 3 hours. Below The treatment was carried out in the same manner as in Example 3, and the compound (]
-(-) -(5) is obtained. Yield: 0.71 g (85%) Example 5 Racemic form of compound (1) 10. OOg to pyridine 10
Example 1
The same treatment as above is carried out to quantitatively obtain the racemate of compound (2).
〔化合物(2)のラセミ体の性質〕
m、p、127〜8℃ 収量14.37 g実施例6
クロロホルム100mlに化合物(2)のラセミ体2.
OOgを溶解し、水冷5〜10℃でm−クロロ過安息
香酸7.50g(85%含有として7.5当量)のクロ
ロホルム75m1の溶液を1時間かけて、攪拌しながら
加える。途中で沈澱が析出する。同温度で1時間攪拌し
た後、室温で一夜攪拌すると沈澱は全部溶解する。過剰
のm−クロロ過安息香酸を5%亜硫酸水素す) IJウ
ム水溶液で分解し、炭酸水素ナトリウム水溶液を加えて
クロロホルム層を抽出する。クロロホルム層を水洗乾燥
し濃縮する。残渣をシリカゲルカラムで精製する〔溶出
液クロロホルム−エタノール(100:1):I。[Properties of racemic form of compound (2)] m, p, 127-8°C Yield: 14.37 g Example 6 Racemic form 2. of compound (2) was added to 100 ml of chloroform.
OOg is dissolved and a solution of 7.50 g (7.5 equivalents based on 85% content) of m-chloroperbenzoic acid in 75 ml of chloroform is added with stirring over a period of 1 hour at 5-10° C., water-cooled. A precipitate separates out during the process. After stirring at the same temperature for 1 hour, the mixture was stirred at room temperature overnight to completely dissolve the precipitate. Excess m-chloroperbenzoic acid is decomposed with a 5% aqueous solution of hydrogen sulfite, and an aqueous sodium bicarbonate solution is added to extract the chloroform layer. The chloroform layer is washed with water, dried and concentrated. The residue is purified on a silica gel column [eluent chloroform-ethanol (100:1):I.
最初に化合物(3)のラセミ体が溶出し、次いで14−
アセトキシ−15(ジアセチルアミノ)メチル−2,8
−ジチア[9] (2,5)ピリジノファンN、S、
S、S’、S’−ペンタオキシド(6)のラセミ体が溶
出される。The racemate of compound (3) elutes first, then 14-
Acetoxy-15(diacetylamino)methyl-2,8
-dithia[9] (2,5)pyridinophane N, S,
The racemic form of S,S',S'-pentaoxide (6) is eluted.
〔化合物(3)のラセミ体の性質〕
mll 202−4℃ 収量0.95g(41%)〔
化合物(6)のラセミ体の性質〕
mp201−2℃(分解) 収量0.97 g(41%
)
UVma、1(C)IC13) 287nm (εI
L、9 X実施例7
エタノール300mlに化合物(2)のラセミ体2.0
0gを溶かし、m−クロロ過安息香酸7.5gのエタノ
ール75mlの混液を攪拌しながら15℃付近で1時間
かけて加える。滴下途中で沈澱が析出し、室温で一夜攪
拌しても沈澱は殆んど溶けない。過剰のm−クロロ過安
息香酸を亜硫酸水素ナトリウム水溶液で分解し、クロロ
ホルム−炭酸水素ナトリウム水溶液で抽出する。クロロ
ホルムを水洗乾燥し濃縮する。残渣をシリカゲルのカラ
ムで精製しく溶出液クロロホルム−メタノール100:
1)、化合物(3)のラセミ体を得る。[Properties of racemic compound (3)] ml 202-4°C Yield 0.95 g (41%) [
Properties of racemic compound (6)] mp 201-2°C (decomposition) Yield 0.97 g (41%
) UVma, 1(C)IC13) 287nm (εI
L, 9
0 g was dissolved, and a mixture of 7.5 g of m-chloroperbenzoic acid and 75 ml of ethanol was added over 1 hour at around 15° C. with stirring. A precipitate was deposited during the dropwise addition, and the precipitate hardly dissolved even after stirring overnight at room temperature. Excess m-chloroperbenzoic acid is decomposed with an aqueous sodium bisulfite solution, and extracted with a chloroform-aqueous sodium bicarbonate solution. Wash the chloroform with water, dry and concentrate. The residue was purified using a silica gel column and the eluent was chloroform-methanol 100:
1) Obtain the racemic compound (3).
収量 1.71g(74%)
実施例8
化合物(6)のラセミ体1.92 gをエタノール20
m1、水10m1と濃塩酸10ml中で攪拌しながら3
時間還流する。活性炭処理をして濃°縮する。Yield 1.71 g (74%) Example 8 1.92 g of racemic compound (6) was dissolved in 20 g of ethanol.
ml, 3 ml with stirring in 10 ml of water and 10 ml of concentrated hydrochloric acid.
Reflux for an hour. Treat with activated carbon and concentrate.
水を加えて水酸化ナトリウム水溶液でpH3として15
−アミノメチル−14−ヒドロキシ−2,8−ジチア[
9コ (2,5)ピリジノファンN、S。Add water and adjust pH to 3 with sodium hydroxide aqueous solution to 15
-aminomethyl-14-hydroxy-2,8-dithia [
9 pieces (2,5) pyridinophane N, S.
s、s’、s’−−ペンタオキシド(7)のラセミ体を
沈澱させ、これを濾別する。The racemic form of s, s', s'--pentaoxide (7) is precipitated and filtered off.
〔化合物(7)のラセミ体の性質〕
mp>280℃ 収量1.38g(97%)LIV、、
、 (IM HCI) 327nm (E4.8 X
10″)、276nm(ε9.Oxl 03)、24
0nm(ε23.7X103)
実施例9
化合物(3)のラセミ体を用いて実施例3と同様に処理
し、化合物(5)およびそのモノ塩酸塩のラセミ体を得
る。[Properties of racemic compound (7)] mp>280°C Yield 1.38g (97%) LIV,
, (IM HCI) 327nm (E4.8
10″), 276nm (ε9.Oxl 03), 24
0 nm (ε23.7×103) Example 9 The racemic form of compound (3) is treated in the same manner as in Example 3 to obtain the racemic form of compound (5) and its monohydrochloride.
〔化合物(5)・HCI のラセミ体の性質3180℃
付近から徐々に溶け、190℃付近から分解し始め、〜
212℃で分解し終る。[Properties of racemic compound (5)/HCI 3180℃
It gradually melts from the vicinity and begins to decompose around 190℃, ~
Decomposition ends at 212°C.
収率 80%
〔化合物(5)のラセミ体の性質3
150℃付近から徐々に溶は始め、175℃付近から分
解し始め、202℃で分解が終る。Yield: 80% [Properties of racemic compound (5) 3: Dissolution begins gradually at around 150°C, decomposition begins at around 175°C, and decomposition ends at 202°C.
収率 はぼ100%Yield: Almost 100%
Claims (3)
ジノファン化合物。 ▲数式、化学式、表等があります▼ 式中、R^1、R^2およびR^3は、独立に、水素原
子またはアセチル基を示す。(1) A pyridoxamine-type pyridinophane compound represented by the following general formula. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In the formula, R^1, R^2 and R^3 independently represent a hydrogen atom or an acetyl group.
数式、化学式、表等があります▼(2) で表される化合物(2)を得、これを酸化剤で処理した
後、必要により脱アセチル化することを特徴とする、下
記の一般式で表されるピリドキサミン型ピリジノファン
化合物の製造法。 ▲数式、化学式、表等があります▼ 上式中、R^1、R^2およびR^3は、独立に、水素
原子またはアセチル基を示す。(2) Formula (1) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (1) By acetylating the compound (1) represented by formula (2) ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼(2) The compound (2) represented by the following general formula is obtained, which is treated with an oxidizing agent and then deacetylated if necessary. A method for producing a pyridoxamine-type pyridinophane compound. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In the above formula, R^1, R^2 and R^3 independently represent a hydrogen atom or an acetyl group.
範囲第2項記載の方法。(3) The method according to claim 2, wherein the oxidizing agent is hydrogen peroxide or a peracid.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP12075885A JPS61277690A (en) | 1985-06-04 | 1985-06-04 | Pyridoxamine type pyridinophane compound and production thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP12075885A JPS61277690A (en) | 1985-06-04 | 1985-06-04 | Pyridoxamine type pyridinophane compound and production thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS61277690A true JPS61277690A (en) | 1986-12-08 |
Family
ID=14794260
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP12075885A Pending JPS61277690A (en) | 1985-06-04 | 1985-06-04 | Pyridoxamine type pyridinophane compound and production thereof |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS61277690A (en) |
-
1985
- 1985-06-04 JP JP12075885A patent/JPS61277690A/en active Pending
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