JPS5953262B2 - New amino acid production method - Google Patents
New amino acid production methodInfo
- Publication number
- JPS5953262B2 JPS5953262B2 JP8692974A JP8692974A JPS5953262B2 JP S5953262 B2 JPS5953262 B2 JP S5953262B2 JP 8692974 A JP8692974 A JP 8692974A JP 8692974 A JP8692974 A JP 8692974A JP S5953262 B2 JPS5953262 B2 JP S5953262B2
- Authority
- JP
- Japan
- Prior art keywords
- pyridone
- group
- hydroxy
- general formula
- formulas
- 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.)
- Expired
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 150000001413 amino acids Chemical class 0.000 title description 7
- -1 benzyl halide Chemical class 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 12
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 claims description 6
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 claims description 4
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- GOPYZMJAIPBUGX-UHFFFAOYSA-N [O-2].[O-2].[Mn+4] Chemical class [O-2].[O-2].[Mn+4] GOPYZMJAIPBUGX-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- GGOZGYRTNQBSSA-UHFFFAOYSA-N pyridine-2,3-diol Chemical compound OC1=CC=CN=C1O GGOZGYRTNQBSSA-UHFFFAOYSA-N 0.000 claims description 2
- 230000002829 reductive effect Effects 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- IEJPPSMHUUQABK-UHFFFAOYSA-N 2,4-diphenyl-4h-1,3-oxazol-5-one Chemical compound O=C1OC(C=2C=CC=CC=2)=NC1C1=CC=CC=C1 IEJPPSMHUUQABK-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 3
- 229940073608 benzyl chloride Drugs 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 125000003172 aldehyde group Chemical group 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 235000011118 potassium hydroxide Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- WZRKSPFYXUXINF-UHFFFAOYSA-N 1-(bromomethyl)-4-methylbenzene Chemical compound CC1=CC=C(CBr)C=C1 WZRKSPFYXUXINF-UHFFFAOYSA-N 0.000 description 1
- PESREEITHIMEMP-UHFFFAOYSA-N 2-aminopropanoic acid 1H-pyridin-2-one Chemical compound CC(N)C(O)=O.O=C1C=CC=CN1 PESREEITHIMEMP-UHFFFAOYSA-N 0.000 description 1
- QLNGBUFFWHFHMU-UHFFFAOYSA-N 3-hydroxy-6-(hydroxymethyl)-1H-pyridin-2-one Chemical compound OCc1ccc(O)c(=O)[nH]1 QLNGBUFFWHFHMU-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 150000001294 alanine derivatives Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- KGCNHWXDPDPSBV-UHFFFAOYSA-N p-nitrobenzyl chloride Chemical compound [O-][N+](=O)C1=CC=C(CCl)C=C1 KGCNHWXDPDPSBV-UHFFFAOYSA-N 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- KIWUVOGUEXMXSV-UHFFFAOYSA-N rhodanine Chemical compound O=C1CSC(=S)N1 KIWUVOGUEXMXSV-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は式目
ＨＯ」ミ□フらＪＭ２−Ｔ−ＣＯＯＨ（Ｉ）ＮＨ、で示
される血圧降下剤として有用な新規アミノ酸β−〔６−
（３−ハイドロオキシー２（ＩＨ）ピリドン）〕−α−
アミノプロピオン酸の製法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention provides a novel amino acid β-[6-
(3-hydroxy-2(IH)pyridone)]-α-
This invention relates to a method for producing aminopropionic acid.
本発明の化合物は既に本発明者等により同じ出発原料で
ある３−ハイドロオキシ−６−ハイドロオキシメチル−
２（１Ｈ）ピリドンから、アシルアミノマロン酸エステ
ル法等により合成されているが（特許出願４９−４６０
１２）その際、３−ハイドロオキシ−６−ハイドロオキ
シメチルー２（１Ｈ）ピリドンのアルキル化反応で２，
３−ジアルキルオキシ−６−ハイドロオキシメチルピリ
ジンを得る過程でＮ−アルキル体の副生が避けられず、
収量の点で必ずしも満足すべき方法ではなかつた。本発
明者等は上記の欠点を考慮し種々検討した結果、より収
率の良い別途合成法を見出し本発明を完成した。The compounds of the present invention have already been prepared by the inventors using the same starting material 3-hydroxy-6-hydroxymethyl-
It has been synthesized from 2(1H) pyridone by the acylaminomalonic acid ester method (Patent Application No. 49-460).
12) At that time, 2,
In the process of obtaining 3-dialkyloxy-6-hydroxymethylpyridine, the by-product of N-alkyl is unavoidable,
This method was not necessarily satisfactory in terms of yield. As a result of various studies in consideration of the above-mentioned drawbacks, the present inventors discovered a separate synthesis method with better yield and completed the present invention.
即ち、本発明によれば、３−ハイドロオキシメチル−２
（１Ｈ）ピリドンにアルコール又は含水アルコール溶液
中、苛性カリ、苛性ソーダ、炭酸ソーダ、炭酸カリ、重
炭酸カリ、トリヱチルアミン等の塩基の存在下にベンジ
ルクロライド、ベンジルプロマイドもしくわＰ−メチル
ベンジルブロマイド、Ｏ−クロロベンジルクロライド、
Ｐ−ニトロベンジルクロライド等の置換ベンジルハライ
ドを作用させると、Ｎ一置換体はほとんど生成せず、ほ
ぼ定量的に３位水酸基のみの置換された、３−ベンジル
オキシ−６−ハイドロオキシメチル−２（１Ｈ）ピリド
ン又は３一置換ベンジルオキシ−６−ハイドロオキシメ
チル−２（１Ｈ）ピリドン（ｌ）が結晶として得られる
。That is, according to the present invention, 3-hydroxymethyl-2
(1H) Add benzyl chloride, benzyl bromide, or P-methylbenzyl bromide, O-chloro to pyridone in alcohol or an aqueous alcohol solution in the presence of a base such as caustic potash, caustic soda, sodium carbonate, potassium carbonate, potassium bicarbonate, or triethylamine. benzyl chloride,
When a substituted benzyl halide such as P-nitrobenzyl chloride is reacted with, almost no N-substituted product is produced, and 3-benzyloxy-6-hydroxymethyl-2 is almost quantitatively substituted with only the hydroxyl group at the 3-position. (1H)pyridone or 3-monosubstituted benzyloxy-6-hydroxymethyl-2(1H)pyridone (l) is obtained as crystals.
（Ｒは水素、メチル基、ハロゲン原子、ニトロ基）かく
して得られた化合糎ｌ）から式（）、ｈ
（Ｒは水素、メチル基、ハ白ゲン原子、ニトロ基））
で示される反応性誘導体３−ベンジルオキシ−６ーホル
ミル−２（１Ｈ）ピリドン又は３一置換ベンジルオキシ
一６−ホルミル−２（１Ｈ）ピリドン（自）を得るには
ハイドロオキシ基をアルデヒド基に酸化する公知の酸化
剤が適用されるが就中、活性二酸化マンガン及び二酸化
セレンによる酸化はピリジン核の１，２位が未保護であ
るにもかかわらず、母核への影響は認められず、好収率
で化合物）を与える。(R is hydrogen, methyl group, halogen atom, nitro group) The thus obtained compound paste has a reactivity shown by the formula (), h (R is hydrogen, methyl group, halogen atom, nitro group) To obtain the derivative 3-benzyloxy-6-formyl-2(1H)pyridone or 3-monosubstituted benzyloxy-6-formyl-2(1H)pyridone (auto), a known oxidizing agent that oxidizes a hydroxy group to an aldehyde group is used. In particular, oxidation with activated manganese dioxide and selenium dioxide had no effect on the mother nucleus, even though the 1st and 2nd positions of the pyridine nucleus were unprotected, and the compound was produced in good yield. give.
本化合物は一般のピリジンアルデヒド類に比べ安定でし
かも結晶性が良く反応液からの単離は容易である。This compound is more stable than general pyridine aldehydes, has good crystallinity, and can be easily isolated from the reaction solution.
本発明のアミノ酸（１）は化合物（自）のピリジン母核
をβ一位に置換したアラニン誘導体であるが化合糎）か
らこの種のアミノ酸合成には芳香族アミノ酸合成で一般
に用いられる、アズラクトン法、ヒダントイン法、ロー
ダニン法等で公知の方法がいずれも適用出来るが、就中
、所謂、アズラクトン法が操作も簡便でしかも収率も優
れていた。The amino acid (1) of the present invention is an alanine derivative in which the pyridine core of the compound (self) is substituted at the β-1 position.This type of amino acid can be synthesized from a compound starch by the azlactone method, which is generally used for aromatic amino acid synthesis. Although any known methods such as , hydantoin method, rhodanine method, etc. can be applied, the so-called azlactone method is particularly easy to operate and has an excellent yield.
Ｎ一アセチルグリシン、又は馬尿酸を使用したアズラク
トン法によつて生成するオキサゾリリデン誘導体は式、
（Ｒは前と同じ意味、Ｋはアセチル基又はベンゾイル基
）で示されるが、原料の化合糎）のアルデヒド基の活性
が高く、一般のアズラクトン縮合の場合よりも比較的低
温下（２０〜５０℃）で収率よくオキサゾリリデン誘導
体を与えることが判つた。Oxazolilidene derivatives produced by the azlactone method using N-acetylglycine or hippuric acid have the formula:
(R has the same meaning as before, K is an acetyl group or a benzoyl group), but the activity of the aldehyde group in the raw material compound starch is high, and the temperature is relatively low (20 to 50 It was found that the oxazolilidene derivatives could be obtained in good yields at temperatures (°C).
化合物（５）は結晶性が良く、反応液からの単離も容易
である。ついでこのオキサゾリリデン誘導体冗）を還元
加水分解することにより本発明の化合物（１）が得られ
るが、このためには接触還元、ついで酸分解、乃至は沃
化水素と赤燐を用いる方法等公知の手段を適用すること
により達成される。Compound (5) has good crystallinity and can be easily isolated from the reaction solution. The compound (1) of the present invention is then obtained by reductive hydrolysis of this oxazolilidene derivative (1), which can be achieved by any known method such as catalytic reduction, then acid decomposition, or a method using hydrogen iodide and red phosphorus. This is achieved by applying means.
かくして得られた化合物１は反応液から酸塩、又は遊解
塩基の結晶として単離される。Compound 1 thus obtained is isolated from the reaction solution as an acid salt or free base crystal.
尚、本物質は不斉炭素を含有しているので本発明は当化
合物の光学活性体及びラセミ混合物を包括するものであ
る。Since this substance contains an asymmetric carbon, the present invention includes optically active forms and racemic mixtures of this compound.
実施例 １
３−ハイドロキシ−６−ハイドロキシメチル−２（１Ｈ
）ピリドン２８９をエタノール３５０ｍ１に懸濁し、こ
のものに苛性カリ２４９を溶解した水溶液１００ｍ１を
加えると均一の溶液を与える。Example 1 3-hydroxy-6-hydroxymethyl-2 (1H
) Pyridone 289 is suspended in 350 ml of ethanol, and 100 ml of an aqueous solution in which caustic potash 249 is dissolved is added to give a homogeneous solution.
次に、この溶液を６５〜７０℃に加温しベンジルクロラ
イド６０ｍ１のエタノール溶液１００ｍ１を攪拌下、２
時間に亘り滴下する。反応をさらに３時間行つた後、反
応液を冷却しＮａＣｌをｆ別する。Next, this solution was heated to 65 to 70°C, and 100 ml of an ethanol solution containing 60 ml of benzyl chloride was added with stirring for 2 hours.
Drip over time. After carrying out the reaction for an additional 3 hours, the reaction solution was cooled and NaCl was removed.
Ｐ液をそのまま濃縮すると、
３−ベンジルオキシ−６−ハイドロキシメチル−２（１
Ｈ）ピリドンの結晶３５９が得られる。When the P solution is directly concentrated, 3-benzyloxy-6-hydroxymethyl-2(1
H) Pyridone crystals 359 are obtained.
融 点：１５７〜１５８℃元素分析値：Ｃ６７．２
６，Ｈ５．８２，Ｎ５．９３％分子式 ：Ｃｌ３Ｈｌ
３ＮＯ３実施例 ２
３−ベンジルオキシ−６−ハイドロキシメチル−２（１
Ｈ）ピリドン２９９をジオキサン４８０ｍ１に懸濁し、
活性二酸化マンガン９０ｇを加え５５℃にて１８時間撹
拌下に反応する。Melting point: 157-158℃ Elemental analysis value: C67.2
6, H5.82, N5.93% Molecular formula: Cl3Hl
3NO3 Example 2 3-benzyloxy-6-hydroxymethyl-2(1
H) Pyridone 299 is suspended in 480 ml of dioxane,
90 g of activated manganese dioxide was added and reacted at 55°C for 18 hours with stirring.
反応終了後反応液をｆ過し、不溶部はジオキサン１００
ｍ１１メタノール１００ｍ１の混液にて洗浄する。沢液
及び洗液を合併し、そのまま濃縮すると結晶が析出する
。クロロホルムエタノールより再結し、
３−ベンジルオキシ−６−ホルミル−２（１Ｈ）ピリド
ンの結晶２１９を得た。After the reaction is completed, the reaction solution is filtered, and the insoluble portion is treated with dioxane 100%.
Wash with a mixed solution of 100 ml of m11 methanol. When the washing liquid and washing liquid are combined and concentrated, crystals will precipitate. Re-crystallization from chloroform-ethanol gave 3-benzyloxy-6-formyl-2(1H)pyridone crystal 219.
融 点：１３６〜１３７。Melting point: 136-137.
Ｃ元素分析値：Ｃ６８．Ｏｌ，Ｈ４．９３，Ｎ６．Ｏ８
％分子式：Ｃｌ３Ｈｌ，ＮＯ３実施例 ３
３−ベンジルオキシ一６−ホルミル−２（１Ｈ）ピリド
ン１２．８９、Ｎ−アセチルグリシン７ｆ！及び新たに
溶融した酢酸ナトリウム５ｇの混合物に無水酢酸１８０
Ｗ１１を加え４０℃にて２時間攪拌する。C elemental analysis value: C68. Ol, H4.93, N6. O8
% Molecular formula: Cl3Hl, NO3 Example 3 3-benzyloxy-6-formyl-2(1H) pyridone 12.89, N-acetylglycine 7f! and 180 g of acetic anhydride to a mixture of 5 g of freshly molten sodium acetate.
Add W11 and stir at 40°C for 2 hours.
反応の途中より多量の結晶が析出するが、さらに結晶析
出を完全ならしむるため、反応液を一夜５℃にて放置し
た。析出した結晶をｆ取し、少量のエタノールで洗浄し
、３−ベンジルオキシ一６−（２−アセチル−５−オキ
ソーオキサゾル４−イリデン）−２（１Ｈ）ピリドンの
淡黄橙色結晶１３９を得た。融 点：２４２〜２４
４℃（融解分解）元素分析値：Ｃ６５．９ｌ，Ｈ４．３
２，Ｎ８，９６％分子式：Ｃｌ，Ｈｌ４Ｎ２Ｏ４実施例
４
苛性ソーダ２１を溶解したアルカリ水溶液１５０ｍ１に
、３−ベンジルオキシ一６−（２−アセチル−５−オキ
ソーオキサゾル一４−イリデン）−２（１Ｈ）ピリドン
９．２９及びラネーニツケル３ｍ１！を加え、４０℃、
５０気圧の条件下で水素添加する。Although a large amount of crystals precipitated during the reaction, the reaction solution was left at 5° C. overnight to ensure complete crystal precipitation. The precipitated crystals were collected and washed with a small amount of ethanol to give pale yellow-orange crystals 139 of 3-benzyloxy-6-(2-acetyl-5-oxooxazol-4-ylidene)-2(1H)pyridone. Obtained. Melting point: 242-24
4℃ (melting decomposition) elemental analysis value: C65.9l, H4.3
2,N8,96% Molecular formula: Cl,Hl4N2O4 Example 4 3-benzyloxy-6-(2-acetyl-5-oxooxazol-4-ylidene)-2( 1H) Pyridone 9.29 and Raney Nickel 3m1! Add, 40℃,
Hydrogenation is carried out under conditions of 50 atm.
反応終了後、反応液を５Ｎ塩酸にて中和し、そのまま濃
縮乾固するとβ−〔６−（３−ハイドロキシ−２（１Ｈ
）ピリドン一α−アミノプロピオン酸のＮ−アセチル体
の粗粉末１０．１９を得る。この粉末６．８９を２０％
塩酸水２０ｄに溶解し、９５〜１００℃にて３時間還流
し、脱Ｎ−アセチル化を行う。反応液を濃縮乾固し、水
−メタノールから結晶化し、β−〔６−（３−ハイドロ
キシ−２（１Ｈ）ピリドン）〕−α−アミノプロピオン
酸の二塩酸塩の結晶を得た。このものを水１５ｍ１に溶
解し、苛性ソーダ水にてＰＨｌ〜２としてエタノールを
添加すると一塩酸塩の結晶が析出する（４．３９）。融
点：２０２〜２０４℃（分解）
元素分析値：Ｃ４Ｏ．８２，Ｈ５．３５，Ｎｌｌ．９ｌ
，Ｃｌｌ５．６ｌ％分子式：Ｃ８ＨｌｌＮ２Ｏ４Ｃｌ
また、この塩酸塩を水に溶解し苛性ソーダ水にてＰＨ７
としそのまま濃縮すると遊離塩基の結晶が析出する。After the reaction, the reaction solution was neutralized with 5N hydrochloric acid and concentrated to dryness to give β-[6-(3-hydroxy-2(1H
) A crude powder 10.19 of the N-acetyl form of pyridone-α-aminopropionic acid is obtained. 20% of this powder 6.89
Dissolve in 20 d of hydrochloric acid water and reflux at 95 to 100°C for 3 hours to perform de-N-acetylation. The reaction solution was concentrated to dryness and crystallized from water-methanol to obtain crystals of β-[6-(3-hydroxy-2(1H)pyridone)]-α-aminopropionic acid dihydrochloride. When this product is dissolved in 15 ml of water, adjusted to pH1~2 with caustic soda water and ethanol is added, monohydrochloride crystals are precipitated (4.39). Melting point: 202-204°C (decomposition) Elemental analysis value: C4O. 82, H5.35, Nll. 9l
, Cll5.6l% Molecular formula: C8HllN2O4Cl Also, dissolve this hydrochloride in water and add caustic soda water to pH 7.
If you concentrate it as it is, crystals of the free base will precipitate.
Claims (1)
２（１Ｈ）ピリドンにベンジルハライドもしくは置換ベ
ンジルハライドを反応させて３位水酸基を選択的に保護
して得られる一般式▲数式、化学式、表等があります▼ （Ｒは水素、メチル基、ハロゲン原子、ニトロ基を示す
）で表わされる化合物に活性二酸化マンガン、二酸化セ
レン等の酸化剤を作用させて酸化し、得られる次の一般
式▲数式、化学式、表等があります▼ （Ｒは前記と同意義） で表わされる化合物にＮ−アセチルグリシン又は馬尿酸
を縮合させて次の一般式▲数式、化学式、表等がありま
す▼ （Ｒは前記と同意義、Ｒ′はアセチル基又はベンゾイル
基を示す）で表わされる化合物を得て、さらにこの化合
物を還元加水分解することを特徴とする、次の式▲数式
、化学式、表等があります▼で表わされるβ−〔６−（
３−ハイドロオキシ−２（１Ｈ）ピリドン）〕−α−ア
ミノプロピオン酸の製造法。[Claims] 1 3-hydroxy-6-hydroxymethyl-
General formula obtained by reacting 2(1H) pyridone with benzyl halide or substituted benzyl halide to selectively protect the 3-position hydroxyl group ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (R is hydrogen, methyl group, halogen atom , indicating a nitro group) is oxidized by the action of an oxidizing agent such as activated manganese dioxide or selenium dioxide, resulting in the following general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R is the same as above) Significance) The compound represented by N-acetylglycine or hippuric acid is condensed to form the following general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (R has the same meaning as above, R' indicates an acetyl group or benzoyl group ) is obtained, and this compound is further subjected to reductive hydrolysis to obtain β-[6-(
A method for producing 3-hydroxy-2(1H)pyridone)]-α-aminopropionic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8692974A JPS5953262B2 (en) | 1974-07-31 | 1974-07-31 | New amino acid production method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8692974A JPS5953262B2 (en) | 1974-07-31 | 1974-07-31 | New amino acid production method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5116676A JPS5116676A (en) | 1976-02-10 |
| JPS5953262B2 true JPS5953262B2 (en) | 1984-12-24 |
Family
ID=13900540
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8692974A Expired JPS5953262B2 (en) | 1974-07-31 | 1974-07-31 | New amino acid production method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5953262B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60244112A (en) * | 1984-05-18 | 1985-12-04 | Mitsubishi Electric Corp | Pulse power supply device |
-
1974
- 1974-07-31 JP JP8692974A patent/JPS5953262B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5116676A (en) | 1976-02-10 |
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