JPH0421674B2 - - Google Patents
Info
- Publication number
- JPH0421674B2 JPH0421674B2 JP59011380A JP1138084A JPH0421674B2 JP H0421674 B2 JPH0421674 B2 JP H0421674B2 JP 59011380 A JP59011380 A JP 59011380A JP 1138084 A JP1138084 A JP 1138084A JP H0421674 B2 JPH0421674 B2 JP H0421674B2
- Authority
- JP
- Japan
- Prior art keywords
- porphyrin compound
- protoporphyrin
- metal salt
- formula
- solution
- 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 - Lifetime
Links
- 150000003839 salts Chemical class 0.000 claims description 25
- -1 porphyrin compound Chemical class 0.000 claims description 21
- 229910052751 metal Inorganic materials 0.000 claims description 15
- 239000002184 metal Substances 0.000 claims description 15
- 230000002378 acidificating effect Effects 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- KSFOVUSSGSKXFI-GAQDCDSVSA-N CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O Chemical compound CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O KSFOVUSSGSKXFI-GAQDCDSVSA-N 0.000 description 11
- 229950003776 protoporphyrin Drugs 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000000243 solution Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000203 mixture Substances 0.000 description 6
- 239000003456 ion exchange resin Substances 0.000 description 5
- 229920003303 ion-exchange polymer Polymers 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- LQBPATQBTSBIIH-UHFFFAOYSA-N methyl 3-[8,13-bis(ethenyl)-18-(3-methoxy-3-oxopropyl)-3,7,12,17-tetramethyl-22,23-dihydroporphyrin-2-yl]propanoate Chemical compound N1C(C=C2C(=C(C=C)C(=CC=3C(=C(CCC(=O)OC)C(=C4)N=3)C)N2)C)=C(C=C)C(C)=C1C=C1C(C)=C(CCC(=O)OC)C4=N1 LQBPATQBTSBIIH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- WPEMLQKWAWUATK-WORMITQPSA-N COCCC=1C(=C2NC=1C=C1C=C(C(=N1)C=C1C=CC(N1)=CC=1C=CC(N=1)=C2)C=C)[2H] Chemical compound COCCC=1C(=C2NC=1C=C1C=C(C(=N1)C=C1C=CC(N1)=CC=1C=CC(N=1)=C2)C=C)[2H] WPEMLQKWAWUATK-WORMITQPSA-N 0.000 description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- GPRXGEKBQVXWAQ-UHFFFAOYSA-L disodium;3-[18-(2-carboxylatoethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethyl-22,23-dihydroporphyrin-2-yl]propanoate Chemical compound [Na+].[Na+].N1C(C=C2C(=C(C)C(=CC=3C(C)=C(CCC([O-])=O)C(N=3)=C3)N2)C=C)=C(C)C(C=C)=C1C=C1C(C)=C(CCC([O-])=O)C3=N1 GPRXGEKBQVXWAQ-UHFFFAOYSA-L 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 2
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- DPEYHNFHDIXMNV-UHFFFAOYSA-N (9-amino-3-bicyclo[3.3.1]nonanyl)-(4-benzyl-5-methyl-1,4-diazepan-1-yl)methanone dihydrochloride Chemical compound Cl.Cl.CC1CCN(CCN1Cc1ccccc1)C(=O)C1CC2CCCC(C1)C2N DPEYHNFHDIXMNV-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000002165 photosensitisation Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002244 precipitate Substances 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
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明はポルフイリン化合物の可溶性塩、更に
詳細には水に易溶な次の一般式（）、
〔式中、R1は−CH＝CH2又は
The present invention relates to soluble salts of porphyrin compounds, more specifically, the following general formula () which is easily soluble in water: [In the formula, R 1 is −CH=CH 2 or
【式】
（Ｒは低級アルキル基を示す）を示す〕
で表わされるポルフイリン化合物のモノアルカリ
金属塩及びその製造法に関する。
（）式中R1がビニル基で表わされるプロト
ポルフイリンはすでに公知の化合物で、肝臓機能
治療剤として使用されているものであり、またプ
ロトポルフイリンの３位のビニル基がアルコリシ
スされた３−アルコキシエチル−８−ビニル−デ
ユウテロポルフイリンは本発明者によつて合成さ
れた新規化合物で、優れたレーザー光増感作用を
有する腫瘍の治療剤として有用な化合物である。
しかしながら、（）式のポルフイリン化合物
及びそのジアルカリ金属塩は水に難溶であり、特
にプロトポルフイリンは注射剤として使用される
ため、これが製剤化の大きな障害となつていた。
そこで、従来、プロトポルフイリンの注射液を
調製するには、プロトポルフイリンを苛性ソーダ
水溶液に溶解し、PHを調整する方法がとられてい
た。しかし、この方法では、プロトポルフイリン
自体を高純度のものとして得ることができないこ
と並びにPHを一定に調整するのが困難なことから
品質を一定に保持することができなかつた。
本発明者は、先にプロトポルフイリンのジアル
カリ金属塩を、高純度に精製したプロトポルフイ
リンジメチルエステルから定量的に得ることに成
功したが、プロトポルフイリンのジアルカリ金属
塩は常塩では水に難溶である。而して当該ジアル
カリ金属塩を水に懸濁し、超音波を施しながら加
温すると透明に溶解するが、放冷すると再び懸濁
状態になるため、これも注射剤とするには不適当
であつた。
斯かる実情において、本発明者は鋭意研究を行
つた結果、（）式のポルフイリン化合物のモノ
アルカリ金属塩が水に易溶性で、冷所に保存して
も沈澱を生じないこと、並びにこの可溶性塩は、
当該ポルフイリン化合物のジアルカリ金属塩を当
モルの該ポルフイリン化合物より酸性度の強い酸
性物質で中和処理することによつて得られること
を見出し、本発明を完成した。
すなわち、本発明は、（）式で表わされるポ
ルフイリン化合物のジアルカリ金属塩の溶液にポ
ルフイリン化合物と当モルの該ポルフイリン化合
物より酸性度の強い酸性物質を加えて処理し、ポ
ルフイリン化合物のモノアルカリ金属塩として収
得することを特徴とするポルフイリン化合物の可
溶性塩の製造法である。
本発明を実施するには、先ずポルフイリン化合
物（）のジアルカリ金属塩を水に懸濁し、超音
波を施しながら、70〜90℃に加温して溶解させ
る。次いでこれに撹拌下酸性物質を加え、ジアル
カリ金属塩の半分を中和する。酸性物質としては
上記ポルフイリン化合物より酸性度の強いもので
あれば何れのものでも使用できるが、弱酸性イオ
ン交換樹脂、酢酸、クエン酸等の弱い酸が好まし
い。酸性物質はポルフイリン化合物（）と当モ
ルあるいはやゝ過剰になるように加え、反応は２
〜５時間行うのが好ましい。反応後、反応混合物
を凍結乾燥等によつて乾燥すれば、ポルフイリン
化合物の可溶性塩が得られる。この可溶性塩は後
述の実施例に示すようにポルフイリン化合物のモ
ノアルカリ金属塩であり、常温あるいは低温にお
いて水及び生理食塩水等に易溶であり、例えば注
射剤を製造する場合に極めて便利である。
次に参考例及び実施例を挙げて説明する。
実施例 １
(i) プロトポルフイリンジナトリウム（純度99％
以上）10ｇを蒸留水3.5に懸濁させ、これに
超音波振動棒を押入し、80℃に加温した。該懸
濁液は30分で透明な溶液となつた。この溶液
に、撹拌下、弱酸性イオン交換樹脂（アンバー
ライトIRC−50：オルガノ株式会社）を活性化
したもの５mlを加え、３時間撹拌した。反応液
からイオン交換樹脂を別し、液を0.2μのメ
ンブランフイルターを通過させ、凍結乾燥して
プロトポルフイリンの可溶性塩９ｇを得た。
(ii) この凍結乾燥物512mg（水分３％）を蒸留水
50mlに溶かし、これに0.1N酢酸50mlを加え、
析出するプロトポルフイリンを別した。この
液50mlを正確にとり、フエノールフタレイン
試薬を３滴加え、0.1N苛性ソーダで逆滴定し
たところ、7.9mlを消費した。従つてこの凍結
乾燥物は3.95％のナトリウムを含み、プロトポ
ルフイリンモノナトリウムであることが確認さ
れた。
実施例 ２
(i) 実施例１の(i)と同様にして調製したプロトポ
ルフイリンジナトリウムの水溶液に、撹拌下99
％酢酸1.0ｇ（1.10モル）を加え、３時間撹拌
した。以下実施例１と同様にして凍結乾燥し、
プロトポルフイリンの可溶性塩9.5ｇを得た。
(ii) この凍結乾燥物34mgを10％塩酸含有メタノー
ル100mlに溶かし、この溶液10mlを25ml容のメ
スフラスコにとり、トリエチルアミン２mlを加
えて中和し、これにジクロルエタンを加えて25
mlとした。この液10μを高速液体クロマトグ
ラフイーに付したところ、プロトポルフイリン
ジメチルエステルと同一の保持時間にピークが
認められ、他にピークは認められなかつた。
実施例 ３
３−メトキシエチル−８−ビニル−デユウテロ
ポルフイリン（MVD）ジナトリウム10ｇを500
mlの蒸留水に懸濁し、これに弱酸性イオン交換樹
脂（実施例１に同じ）を活性化したもの５mlを加
え、３時間撹拌した。イオン交換樹脂を去し、
液を0.2μのメンブランフイルターを通過させた
後、凍結乾燥して３−メトキシエチル−８−ビニ
ル−デユウテロポルフイリンの可溶性塩9.2ｇを
得た。実施例１の(ii)と同様にして測定したとこ
ろ、モノナトリウム塩であつた。
参考例
(i) プロトポルフイリンジメチルエステル１ｇを
メタノール500mlに懸濁し、これに塩化水素ガ
スを導入して飽和させ、３時間煮沸した。これ
を10％炭酸アンモニウム水溶液１に注加し、
ジクロルエタン200mlで抽出し、抽出液を水洗
後、硫酸ナトリウムで乾燥した。この抽出液
を、予めジクロルエタンで洗浄したシリカゲル
カラムに注加して吸着させ、ジクロルエタンで
溶出を行つた。最初に原料のプロトポルフイリ
ンジメチルエステルが溶出された。
(ii) 第２に溶出されるフラクシヨン（TLCで単
一スポツトであることを確認）を集め、溶媒を
留去し、残留物をトルエンより再結晶して、
MVDジメチルエステル0.13ｇ（収率13％）を
得た。
元素分析値 C37H42N4O5
計算値（％）：Ｃ：71.36，Ｈ：6.80，Ｎ：
9.00
実測値（％）：Ｃ：71.31，Ｈ：6.93，Ｎ：
9.02
Mass：Calcd622Found623（Ｍ＋１）
NMR（400MHz，in CDcl3）ppm
10.54（1H，ｓ，５−CH）
10.08（1H，ｓ，10−CH）
10.06（1H，ｓ，20−CH）
9.92（1H，ｓ，15−CH）
8.27，8.24，8.23，8.20（1H，ｄ，81−CH）
6.36，6.31（1H，ｄ，82−CH2）
6.16，6.15（1H，ｄ，82−CH2）
6.13，6.12，6.06，6.04（1H，ｑ，31−CH）
4.34，4.32，4.30，4.28（4H，ｑ，131，171−
CH2−）
3.72（3H，ｓ，７−CH3）
3.69（3H，ｓ，２−CH3）
3.63（6H，ｓ，133，173エステル−OCH3）
3.60（3H，ｓ，31−OCH3）
3.57（3H，ｓ，12−CH3）
3.52（3H，ｓ，18−CH3）
3.23，3.22，3.21，3.20（4H，ｑ，132，172−
CH2−）
2.27，2.25（3H，ｄ，32−CH3）
−3.76（2H，ｓ，Ｎ−Ｈ）
(iii) (ii)で得たMVDジメチルエステル１ｇをピリ
ジン50mlに溶かし、苛性ソーダ20mgのメタノー
ル溶液を加え、90℃で２時間撹拌した。反応後
析出した結晶を取し、乾燥し、MVDジナト
リウム0.1ｇを得た。The present invention relates to a monoalkali metal salt of a porphyrin compound represented by the formula: (R represents a lower alkyl group) and a method for producing the same. Protoporphyrin in which R 1 is represented by a vinyl group in the formula () is already a known compound and is used as a liver function treatment agent. -Alkoxyethyl-8-vinyl-deuteroporphyrin is a novel compound synthesized by the present inventor, and is a compound useful as a tumor therapeutic agent having an excellent laser photosensitizing effect. However, the porphyrin compound of the formula () and its dialkali metal salt are sparingly soluble in water, and this has been a major obstacle to formulation, especially since protoporphyrin is used as an injection. Therefore, conventionally, in order to prepare an injection solution of protoporphyrin, protoporphyrin was dissolved in an aqueous solution of caustic soda and the pH was adjusted. However, with this method, it was not possible to maintain a constant quality because protoporphyrin itself could not be obtained in a highly pure form and it was difficult to adjust the pH to a constant level. The present inventors previously succeeded in quantitatively obtaining the dialkali metal salt of protoporphyrin from highly purified protoporphyrin dimethyl ester, but the dialkali metal salt of protoporphyrin does not dissolve in water in ordinary salt. It is hardly soluble. When the dialkali metal salt is suspended in water and heated while being subjected to ultrasound, it dissolves transparently, but when it is left to cool, it becomes suspended again, making it unsuitable for use as an injection. Ta. Under these circumstances, the present inventor conducted extensive research and found that the monoalkali metal salt of the porphyrin compound of formula () is easily soluble in water and does not form a precipitate even when stored in a cool place, and that this solubility The salt is
The present invention was completed by discovering that the dialkali metal salt of the porphyrin compound can be obtained by neutralizing it with an acidic substance that is more acidic than the equivalent molar amount of the porphyrin compound. That is, in the present invention, a solution of a dialkali metal salt of a porphyrin compound represented by the formula (2) is treated by adding an acidic substance that is more acidic than the porphyrin compound in the same molar amount as the porphyrin compound, to obtain a monoalkali metal salt of a porphyrin compound. This is a method for producing a soluble salt of a porphyrin compound, characterized in that it is obtained as a porphyrin compound. To carry out the present invention, first, a dialkali metal salt of a porphyrin compound () is suspended in water, and heated to 70 to 90° C. while applying ultrasound to dissolve it. Next, an acidic substance is added to this while stirring to neutralize half of the dialkali metal salt. As the acidic substance, any substance having stronger acidity than the above-mentioned porphyrin compounds can be used, but weak acids such as weakly acidic ion exchange resins, acetic acid, and citric acid are preferable. The acidic substance is added in an equimolar amount or in slight excess with the porphyrin compound (), and the reaction is 2
It is preferable to carry out for ~5 hours. After the reaction, the reaction mixture is dried by freeze-drying or the like to obtain a soluble salt of the porphyrin compound. As shown in the Examples below, this soluble salt is a monoalkali metal salt of a porphyrin compound, and is easily soluble in water, physiological saline, etc. at room temperature or low temperature, and is extremely convenient for producing injections, for example. . Next, reference examples and examples will be given and explained. Example 1 (i) Protoporphyrin disodium (purity 99%)
10g of the above) was suspended in 3.5ml of distilled water, an ultrasonic vibrating rod was inserted into the suspension, and the mixture was heated to 80°C. The suspension became a clear solution in 30 minutes. To this solution, 5 ml of activated weakly acidic ion exchange resin (Amberlite IRC-50: Organo Co., Ltd.) was added while stirring, and the mixture was stirred for 3 hours. The ion exchange resin was separated from the reaction solution, the solution was passed through a 0.2μ membrane filter, and lyophilized to obtain 9 g of a soluble salt of protoporphyrin. (ii) 512 mg (3% moisture) of this freeze-dried product was mixed with distilled water.
Dissolve in 50ml, add 50ml of 0.1N acetic acid,
The precipitated protoporphyrin was separated. When 50 ml of this liquid was accurately taken, 3 drops of phenolphthalein reagent was added, and the mixture was back titrated with 0.1N caustic soda, 7.9 ml was consumed. Therefore, this freeze-dried product contained 3.95% sodium and was confirmed to be protoporphyrin monosodium. Example 2 (i) To an aqueous solution of protoporphyrin disodium prepared in the same manner as in (i) of Example 1, 99% was added under stirring.
% acetic acid (1.10 mol) was added and stirred for 3 hours. The following was freeze-dried in the same manner as in Example 1,
9.5 g of soluble salt of protoporphyrin was obtained. (ii) Dissolve 34 mg of this lyophilized product in 100 ml of methanol containing 10% hydrochloric acid, add 10 ml of this solution to a 25 ml volumetric flask, add 2 ml of triethylamine to neutralize it, add dichloroethane to it,
ml. When 10μ of this solution was subjected to high performance liquid chromatography, a peak was observed at the same retention time as protoporphyrin dimethyl ester, and no other peaks were observed. Example 3 10 g of 3-methoxyethyl-8-vinyl deuteroporphyrin (MVD) disodium was added to 500
ml of distilled water, 5 ml of activated weakly acidic ion exchange resin (same as in Example 1) was added thereto, and the mixture was stirred for 3 hours. Remove the ion exchange resin,
The solution was passed through a 0.2μ membrane filter and then lyophilized to obtain 9.2g of a soluble salt of 3-methoxyethyl-8-vinyl-deuteroporphyrin. When measured in the same manner as in Example 1 (ii), it was found to be a monosodium salt. Reference Example (i) 1 g of protoporphyrin dimethyl ester was suspended in 500 ml of methanol, hydrogen chloride gas was introduced into the suspension to saturate the suspension, and the suspension was boiled for 3 hours. Pour this into 10% ammonium carbonate aqueous solution 1,
Extraction was performed with 200 ml of dichloroethane, and the extract was washed with water and dried over sodium sulfate. This extract was poured onto a silica gel column that had been previously washed with dichloroethane to be adsorbed, and elution was performed with dichloroethane. The raw material protoporphyrin dimethyl ester was eluted first. (ii) The second eluting fraction (confirmed to be a single spot by TLC) was collected, the solvent was distilled off, and the residue was recrystallized from toluene.
0.13 g (13% yield) of MVD dimethyl ester was obtained. Elemental analysis value C 37 H 42 N 4 O 5 Calculated value (%): C: 71.36, H: 6.80, N:
9.00 Actual value (%): C: 71.31, H: 6.93, N:
9.02 Mass: Calcd622Found623 (M+1) NMR (400MHz, in CDcl 3 ) ppm 10.54 (1H, s, 5-CH) 10.08 (1H, s, 10-CH) 10.06 (1H, s, 20-CH) 9.92 (1H, s, 15-CH) 8.27, 8.24, 8.23, 8.20 (1H, d, 8 1 -CH) 6.36, 6.31 (1H, d, 8 2 -CH 2 ) 6.16, 6.15 (1H, d, 8 2 -CH 2 ) 6.13, 6.12, 6.06, 6.04 (1H, q, 3 1 − CH) 4.34, 4.32, 4.30, 4.28 (4H, q, 13 1 , 17 1 −
CH 2 −) 3.72 (3H, s, 7-CH 3 ) 3.69 (3H, s, 2-CH 3 ) 3.63 (6H, s, 13 3 , 17 3 ester-OCH 3 ) 3.60 (3H, s, 3 1 −OCH 3 ) 3.57 (3H, s, 12−CH 3 ) 3.52 (3H, s, 18−CH 3 ) 3.23, 3.22, 3.21, 3.20 (4H, q, 13 2 , 17 2 −
CH 2 −) 2.27, 2.25 (3H, d, 3 2 −CH 3 ) −3.76 (2H, s, N−H) (iii) Dissolve 1 g of MVD dimethyl ester obtained in (ii) in 50 ml of pyridine, and add 20 mg of caustic soda. A methanol solution of was added, and the mixture was stirred at 90°C for 2 hours. After the reaction, the precipitated crystals were collected and dried to obtain 0.1 g of MVD disodium.
Claims (1)
金属塩。 ２ 一般式 〔式中、R1は−CH＝CH2又は【式】 （Ｒは低級アルキル基を示す）を示す〕 で表わされるポルフイリン化合物のジアルカリ金
属塩の溶液にポルフイリン化合物と当モルの該ポ
ルフイリン化合物より酸性度の強い酸性物質を加
えて処理し、ポルフイリン化合物のモノアルカリ
金属塩として単離収得することを特徴とするポル
フイリン化合物の可溶性塩の製造法。[Claims] 1. General formula A monoalkali metal salt of a porphyrin compound represented by [wherein R 1 represents -CH=CH 2 or [formula] (R represents a lower alkyl group)]. 2 General formula [In the formula, R 1 represents -CH=CH 2 or [Formula] (R represents a lower alkyl group)] In a solution of a dialkali metal salt of a porphyrin compound represented by 1. A method for producing a soluble salt of a porphyrin compound, which is characterized in that the porphyrin compound is isolated and obtained as a monoalkali metal salt by treatment with a highly acidic substance.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1138084A JPS60156690A (en) | 1984-01-25 | 1984-01-25 | Preparation of soluble salt of porphyrin compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1138084A JPS60156690A (en) | 1984-01-25 | 1984-01-25 | Preparation of soluble salt of porphyrin compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60156690A JPS60156690A (en) | 1985-08-16 |
| JPH0421674B2 true JPH0421674B2 (en) | 1992-04-13 |
Family
ID=11776402
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1138084A Granted JPS60156690A (en) | 1984-01-25 | 1984-01-25 | Preparation of soluble salt of porphyrin compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60156690A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61186385A (en) * | 1985-02-13 | 1986-08-20 | Sato Yakugaku Kenkyusho:Kk | Deuteroporphyrin derivative and its salt |
| JPH0720963B2 (en) * | 1986-01-17 | 1995-03-08 | 浜理薬品工業株式会社 | Porphyrin derivative |
| JPH0714942B2 (en) * | 1986-03-03 | 1995-02-22 | 浜理薬品工業株式会社 | Porphyrin derivative |
| JP2520735B2 (en) * | 1988-07-14 | 1996-07-31 | 東洋薄荷工業株式会社 | Porphyrin derivative |
| WO2024050694A1 (en) * | 2022-09-06 | 2024-03-14 | 南京百特生物工程有限公司 | Natural porphin salt and use thereof as plant growth regulator and immune resistance inducer |
-
1984
- 1984-01-25 JP JP1138084A patent/JPS60156690A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60156690A (en) | 1985-08-16 |
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