JPS6136817B2 - - Google Patents
Info
- Publication number
- JPS6136817B2 JPS6136817B2 JP18614480A JP18614480A JPS6136817B2 JP S6136817 B2 JPS6136817 B2 JP S6136817B2 JP 18614480 A JP18614480 A JP 18614480A JP 18614480 A JP18614480 A JP 18614480A JP S6136817 B2 JPS6136817 B2 JP S6136817B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- water
- compound
- formula
- mol
- 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
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- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 208000025865 Ulcer Diseases 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 231100000397 ulcer Toxicity 0.000 description 5
- -1 2,3-butanediol diester Chemical class 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000000767 anti-ulcer Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229940126208 compound 22 Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- WOGITNXCNOTRLK-VOTSOKGWSA-N (e)-3-phenylprop-2-enoyl chloride Chemical compound ClC(=O)\C=C\C1=CC=CC=C1 WOGITNXCNOTRLK-VOTSOKGWSA-N 0.000 description 1
- KNUNDVBNLCGWPK-UHFFFAOYSA-N 2-cyano-3-phenylprop-2-enoyl chloride Chemical compound ClC(=O)C(C#N)=CC1=CC=CC=C1 KNUNDVBNLCGWPK-UHFFFAOYSA-N 0.000 description 1
- OUVTVAYAMIIJCQ-UHFFFAOYSA-N 3-(4-methoxyphenyl)prop-2-enoic acid;hydrochloride Chemical compound Cl.COC1=CC=C(C=CC(O)=O)C=C1 OUVTVAYAMIIJCQ-UHFFFAOYSA-N 0.000 description 1
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
- DPQCZNIGGNJGTD-UHFFFAOYSA-N Chloride-(??)-2-Methylpentanoic acid Natural products CCCCCCC=CCCCCCCCCCC(=O)OC(C)C(C)OC(=O)CCCCCCCC=CCCCCCC DPQCZNIGGNJGTD-UHFFFAOYSA-N 0.000 description 1
- DPQCZNIGGNJGTD-MVCBGFDASA-N Coixenolide Chemical compound CCCCCC\C=C\CCCCCCCCCC(=O)O[C@@H](C)[C@@H](C)OC(=O)CCCCCCC\C=C/CCCCCC DPQCZNIGGNJGTD-MVCBGFDASA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JUKPJGZUFHCZQI-UHFFFAOYSA-N undecanoyl chloride Chemical compound CCCCCCCCCCC(Cl)=O JUKPJGZUFHCZQI-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は、新規な２，３―ブタンジオールジエ
ステル誘導体並びにその製造法に関する。
従来、２，３―ブタンジオールジエステル誘導
体には、〓苡仁の抗腫瘍成分として知られるコイ
クセノリドの他、数種の脂肪酸ジエステル類が知
られているにすぎず、それらの薬理作用について
は、全く知られていなかつた。
本発明者らは、当該誘導体について鋭意研究を
行つた結果、次の一般式（）、
〔式中、R1は、水素原子、低級アルキル基又
はシアノ基を、R2はハロゲン原子、低級アルキ
ル基、低級アルキルカルボニルオキシ基あるいは
低級アルコキシ基の１又は２以上を置換基として
有していても良いフエニル基を、R3はアルキル
基、アルケニル基又は
The present invention relates to a novel 2,3-butanediol diester derivative and a method for producing the same. Until now, only a few types of fatty acid diesters have been known as 2,3-butanediol diester derivatives, in addition to coixenolide, which is known as an antitumor component of ``Kojin'', and nothing is known about their pharmacological effects. It wasn't. As a result of intensive research on the derivatives, the present inventors found the following general formula (), [In the formula, R 1 has a hydrogen atom, a lower alkyl group, or a cyano group, and R 2 has one or more of a halogen atom, a lower alkyl group, a lower alkylcarbonyloxy group, or a lower alkoxy group as a substituent. R 3 is an alkyl group, an alkenyl group, or a phenyl group, which may be
【式】（式中
R1及びR2は前記と同じ）基を示す〕
で表わされる化合物が、消化性潰瘍の発生を強力
に抑制することを見い出し、本発明を完成した。
すなわち、本発明の目的は、優れた消化性潰瘍
の予防及び治療薬として有用な（）式の化合物
を提供せんとするものにある。
本発明化合物の一般式（）において、R2の
フエニル基に置換される基としては、例えば、ハ
ロゲン原子、アルキル基、アシルオキシ基又はア
ルコキシ基等が挙げられ、これらは１個又は２個
以上が置換してもよい。
本発明化合物（）は、例えば次の何れかの方
法によつて製造される。
２，３―ブタンジオール（）にカルボン酸
（）又はその活性誘導体を反応させて２，３
―ブタンジオールモノエステル誘導体（）と
なし、次いでこれにカルボン酸（）又はその
活性誘導体を反応させて目的物（）を得る。
（式中、R1，R2及びR3は前記に同じ）
２，３―ブタンジオール（）にカルボン酸
（）又はそのの活性誘導体を反応させて２，
３―ブタンジオールモノエステル誘導体（）
となし、次いでこれにカルボン酸（）又はそ
の活性誘導体を反応させて目的物（）を得
る。
（式中、R1，R2及びR3は前記と同じ）
２，３―ブタンジオール（）に２倍モルの
カルボン酸（）又はその活性誘導体を反応さ
せて２，３―ブタンジオールジエステル誘導体
（′）を得る。
（式中、R1及びR2は前記に同じ）
本方法において、カルボン酸（）及び（）
の活性誘導体としては、酸ハロゲニド、酸無水
物、混合酸無水物等が挙げられ、この場合、反応
はピリジン、三級アミン、炭酸アルカリ、水酸化
アルカリ、水素化アルカリ等の脱酸剤剤の存在下
行うのが好ましい。
斯くの如くして得られる本発明化合物（）の
抗潰瘍作用を試験した結果は、次のとおりであ
る。
体重約200ｇのウイスター系雄性ラツトを24時
間絶食して実験を行つた。即ち、インドメタシン
を１％カルボキシメチルセルロースナトリウム水
溶液にて懸濁し25mg／Kgを経口投与した。５時間
後に２％ブリリアントブルー生理食塩水溶液１ml
を尾静脈内に注入し、10分後に屠殺して全胃を摘
出した。その後１％ホルマリン水溶液12mlを注入
して固定後、平板上に拡げて胃体部に発生した損
傷部をノギスで計測し、その長さ（mm）の総和を
もつて潰瘍係数とした。
なお被検化合物は、ポリソルベート80 １滴を
加えた生理食塩水にて乳化又は懸濁し、インドメ
タシン投与の１時間前に経口投与又は背部に皮下
注射を行つた。
潰瘍の抑制率は次式により求めた。
抑制率（％）＝コントロール群の潰瘍係数−被検化合物投与群の潰瘍係数／コントロール群の潰瘍係数×100
結果を第１表に示した。尚化合物No.は第２表に
示すものを意味する。The present invention has been completed based on the discovery that a compound represented by the formula: (in which R 1 and R 2 are the same as above) strongly suppresses the occurrence of peptic ulcers. That is, an object of the present invention is to provide a compound of formula () that is useful as an excellent preventive and therapeutic agent for peptic ulcers. In the general formula () of the compound of the present invention, examples of the group substituted with the phenyl group of R2 include a halogen atom, an alkyl group, an acyloxy group, or an alkoxy group, in which one or more May be replaced. The compound of the present invention () can be produced, for example, by any of the following methods. 2,3-butanediol (2) is reacted with carboxylic acid (2) or its active derivative to produce 2,3
-Butanediol monoester derivative () is then reacted with carboxylic acid () or its active derivative to obtain the desired product (). (In the formula, R 1 , R 2 and R 3 are the same as above) 2,3-butanediol () is reacted with a carboxylic acid () or an active derivative thereof, and 2,
3-butanediol monoester derivative ()
Then, the desired product () is obtained by reacting the carboxylic acid () or an active derivative thereof with the carboxylic acid (). (In the formula, R 1 , R 2 and R 3 are the same as above) 2,3-butanediol diester derivative is obtained by reacting 2,3-butanediol () with twice the mole of carboxylic acid () or its active derivative. (') is obtained. (In the formula, R 1 and R 2 are the same as above.) In this method, carboxylic acid () and ()
Examples of active derivatives include acid halogenides, acid anhydrides, mixed acid anhydrides, etc. In this case, the reaction is carried out using deoxidizing agents such as pyridine, tertiary amines, alkali carbonates, alkali hydroxides, and alkali hydrides. Preferably, it is carried out in the presence of The results of testing the anti-ulcer effect of the compound () of the present invention thus obtained are as follows. The experiment was conducted using male Wistar rats weighing approximately 200 g, which were fasted for 24 hours. That is, indomethacin was suspended in a 1% sodium carboxymethyl cellulose aqueous solution and 25 mg/Kg was orally administered. After 5 hours, add 1 ml of 2% brilliant blue saline solution.
was injected into the tail vein, and 10 minutes later, the animals were sacrificed and the entire stomach was removed. After fixation by injecting 12 ml of a 1% formalin aqueous solution, it was spread out on a flat plate, and the damaged area in the stomach body was measured with a caliper, and the sum of the lengths (mm) was taken as the ulcer index. The test compound was emulsified or suspended in physiological saline to which one drop of polysorbate 80 was added, and was administered orally or subcutaneously injected into the back one hour before administration of indomethacin. The ulcer suppression rate was calculated using the following formula. Inhibition rate (%) = Ulcer coefficient of control group - Ulcer coefficient of test compound administration group / Ulcer coefficient of control group x 100 The results are shown in Table 1. In addition, compound No. means what is shown in Table 2.
【表】
以上の如く、本発明化合物は強い抗潰瘍作用を
有する。
次に本発明の実施例を挙げて説明する。
実施例 １（化合物１の合成）
２，３―ブタンジオール９ｇ（0.1モル）をエ
ーテル50mlに溶解し、ピリジン10mlを加え、氷冷
撹拌下ケイヒ酸クロリド16.65ｇ（0.1モル）のエ
ーテル溶液30mlを滴下した。同温度で30分、更に
室温に戻して４時間撹拌後、水を加えてエーテル
層を分取した。エーテル層を、水、10％塩酸、
水、飽和炭酸水素ナトリウム溶液、水の順に洗
い、無水硫酸ナトリウムで乾燥した。エーテルを
減圧下留去し、残渣をカラムクロマトグラフイー
（SiO2）にて精製し、無色液体のモノエステル体
9.4ｇ（収率42.7％）を得た。
このモノエステル体9.4ｇ（0.043モル）をエー
テル120mlに溶解し、ピリジン6.8mlを加え、氷冷
下撹拌しながら、カプロン酸クロリド5.75ｇ
（0.043モル）のエーテル溶液120mlを滴下した。
同温度で30分、更に室温に戻して４時間撹拌後、
水を加えてエーテル層を分取した。エーテル層を
水、10％塩酸、水、飽和炭酸水素ナトリウム溶
液、水の順に洗い、無水硫酸ナトリウムで乾燥し
た。エーテルを減圧下留去し、残渣をカラムクロ
マトグラフイー（SiO2）にて精製し、無色液体の
第２表記載の化合物１を9.3ｇ（収率71％）得
た。
ｎ２０ Ｄ1.514 IR νｎｅａｔ ｎａｘcm-11720（Ｃ＝
０）
実施例 ２（化合物14の合成）
水素化ナトリウム４ｇ（0.1モル）をエーテル
40に懸濁し、氷冷撹拌下２，３―ブタンジオー
ル９ｇ（0.1モル）のエーテル溶液40mlを滴下し
た。同温度で30分、室温で30分撹拌した後、再び
氷冷しウンデカノイルクロリド20.45ｇ（0.1モ
ル）のエーテル溶液40mlを滴下し、室温に戻して
３時間撹拌後水を加えてエーテル層を分取した。
以下実施例１と同様に処理して無色液体のモノエ
ステル体10.5ｇ（収率40.7％）を得た。このモノ
エステル体10.32ｇ（0.04モル）をテトラヒドロ
フラン80mlに溶解し、ピリジン6.4mlを加え、氷
冷撹拌下ｐ―メトキシケイヒ酸クロリド7.86ｇ
（0.04モル）のテトラヒドロフラン溶液80mlを滴
下した。同温度で30分更に室温に戻して４時間撹
拌後、溶媒を減圧下留去し、残渣をクロロホルム
に転溶して、水、10％塩酸、水、飽和炭酸水素ナ
トリウム溶液、水の順に無水硫酸ナトリウムで乾
燥した。クロロホルムを減圧下留去し、残渣をカ
ラムクロマトグラフイー（SiO2）にて精製し、無
色液体の第２表記載の化合物14を６ｇ（収率35.8
％）得た。
ｎ２０ Ｄ 1.519 IR νｎｅａｔ ｎａｘcm-1 1720（
Ｃ＝０）
実施例 ３（化合物22の合成）
２，３―ブタンジオール4.5ｇ（0.05モル）を
テトラヒドロフラン60mlに溶解し、ピリジン10ml
を加え、氷冷撹拌下、α―シアノケイヒ酸クロリ
ド19.15ｇ（0.1モル）のテトラヒドロフラン溶液
60mlを滴下した。同温度で30分、更に室温に戻し
て４時間撹拌後、溶媒を減圧下留去し、残渣をク
ロロホルムに転溶した。クロロホルム層を水、10
％塩酸、水、飽和炭酸水素ナトリウム溶液、水の
順に洗い、無水硫酸ナトリウムで乾燥した。クロ
ロホルムを減圧下留去し、残渣をベンゼンから再
結晶して、淡黄色針状晶の第２表記載の化合物22
を12.4ｇ（収率62％）得た。
融点177〜180℃
IR νＫＢｒ ｎａｘ cm-1 1720（Ｃ＝０）
実施例 ４
実施例１，２又は３と同様にして第２表の化合
物を得た。尚表中には実施例１〜３で得た化合物
もあわせて記載した。[Table] As described above, the compounds of the present invention have strong anti-ulcer effects. Next, examples of the present invention will be described. Example 1 (Synthesis of Compound 1) 9 g (0.1 mol) of 2,3-butanediol was dissolved in 50 ml of ether, 10 ml of pyridine was added, and 30 ml of an ether solution of 16.65 g (0.1 mol) of cinnamic acid chloride was added under stirring under ice cooling. dripped. After stirring at the same temperature for 30 minutes, and then returning to room temperature for 4 hours, water was added and the ether layer was separated. ether layer, water, 10% hydrochloric acid,
It was washed with water, saturated sodium bicarbonate solution, and water in this order, and dried over anhydrous sodium sulfate. The ether was distilled off under reduced pressure, and the residue was purified by column chromatography (SiO 2 ) to obtain a colorless liquid monoester.
9.4 g (yield 42.7%) was obtained. Dissolve 9.4 g (0.043 mol) of this monoester in 120 ml of ether, add 6.8 ml of pyridine, and add 5.75 g of caproic acid chloride while stirring under ice cooling.
120 ml of an ether solution of (0.043 mol) was added dropwise.
After stirring at the same temperature for 30 minutes and then returning to room temperature for 4 hours,
Water was added and the ether layer was separated. The ether layer was washed successively with water, 10% hydrochloric acid, water, saturated sodium bicarbonate solution, and water, and dried over anhydrous sodium sulfate. The ether was distilled off under reduced pressure, and the residue was purified by column chromatography (SiO 2 ) to obtain 9.3 g (yield 71%) of Compound 1 listed in Table 2 as a colorless liquid. n 20 D 1.514 IR ν neat nax cm -1 1720 (C=
0) Example 2 (synthesis of compound 14) 4 g (0.1 mol) of sodium hydride was dissolved in ether
40 ml of an ether solution containing 9 g (0.1 mol) of 2,3-butanediol was added dropwise while stirring under ice cooling. After stirring at the same temperature for 30 minutes and at room temperature for 30 minutes, the mixture was cooled on ice again, and 40 ml of an ether solution containing 20.45 g (0.1 mol) of undecanoyl chloride was added dropwise. After returning to room temperature and stirring for 3 hours, water was added to form an ether layer. was fractionated.
Thereafter, the same treatment as in Example 1 was carried out to obtain 10.5 g (yield: 40.7%) of a colorless liquid monoester. 10.32 g (0.04 mol) of this monoester was dissolved in 80 ml of tetrahydrofuran, 6.4 ml of pyridine was added, and 7.86 g of p-methoxycinnamate chloride was added under stirring under ice cooling.
(0.04 mol) in tetrahydrofuran was added dropwise. After stirring at the same temperature for 30 minutes and returning to room temperature for 4 hours, the solvent was distilled off under reduced pressure, and the residue was dissolved in chloroform, followed by water, 10% hydrochloric acid, water, saturated sodium bicarbonate solution, and water. Dry with sodium sulfate. Chloroform was distilled off under reduced pressure, and the residue was purified by column chromatography (SiO 2 ) to obtain 6 g of Compound 14 listed in Table 2 as a colorless liquid (yield: 35.8
%)Obtained. n 20 D 1.519 IR ν neat nax cm -1 1720 (
C=0) Example 3 (Synthesis of Compound 22) 4.5 g (0.05 mol) of 2,3-butanediol was dissolved in 60 ml of tetrahydrofuran, and 10 ml of pyridine was dissolved.
A solution of 19.15 g (0.1 mol) of α-cyanocinnamic acid chloride in tetrahydrofuran was added under ice-cooling and stirring.
60 ml was added dropwise. After stirring at the same temperature for 30 minutes, and then returning to room temperature for 4 hours, the solvent was distilled off under reduced pressure, and the residue was dissolved in chloroform. Add chloroform layer to water, 10
% hydrochloric acid, water, saturated sodium bicarbonate solution, and water, and dried over anhydrous sodium sulfate. Chloroform was distilled off under reduced pressure, and the residue was recrystallized from benzene to give compound 22 listed in Table 2 as pale yellow needle-like crystals.
12.4g (yield 62%) was obtained. Melting point: 177-180°C IR ν KBr nax cm -1 1720 (C=0) Example 4 The compounds shown in Table 2 were obtained in the same manner as in Example 1, 2 or 3. In addition, the compounds obtained in Examples 1 to 3 are also listed in the table.
【表】【table】
【表】【table】
【表】【table】
Claims (1)
はシアノ基を、R2はハロゲン原子、低級アルキ
ル基、低級アルキルカルボニルオキシ基あるいは
低級アルコキシ基の１又は２以上を置換基して有
していても良いフエニル基を、R3はアルキル
基、アルケニル基又は 【式】（式中R1及びR2は前記と同 じ）基を示す〕 で表わされる２，３―ブタンジオールジエステル
誘導体。[Claims] 1. General formula [In the formula, R 1 has a hydrogen atom, a lower alkyl group, or a cyano group, and R 2 has one or more substituents of a halogen atom, a lower alkyl group, a lower alkylcarbonyloxy group, or a lower alkoxy group. R 3 represents an alkyl group, an alkenyl group, or a group [formula] (wherein R 1 and R 2 are the same as above).
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18614480A JPS57109742A (en) | 1980-12-26 | 1980-12-26 | Butanediol derivative and its preparation |
| US06/333,772 US4469704A (en) | 1980-12-26 | 1981-12-23 | 2,3-Butanediol diester derivatives, process for producing the same, and an antiulcer drug containing the same |
| EP81306100A EP0056189B1 (en) | 1980-12-26 | 1981-12-23 | 2,3-butanediol diester derivatives, process for producing the same, and an antiulcer drug containing the same |
| DE8181306100T DE3175184D1 (en) | 1980-12-26 | 1981-12-23 | 2,3-butanediol diester derivatives, process for producing the same, and an antiulcer drug containing the same |
| US06/572,242 US4548753A (en) | 1980-12-26 | 1984-01-20 | 2,3-Butanediol diester derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18614480A JPS57109742A (en) | 1980-12-26 | 1980-12-26 | Butanediol derivative and its preparation |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10977881A Division JPS57109719A (en) | 1980-12-26 | 1981-07-14 | Antiulcer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57109742A JPS57109742A (en) | 1982-07-08 |
| JPS6136817B2 true JPS6136817B2 (en) | 1986-08-20 |
Family
ID=16183143
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP18614480A Granted JPS57109742A (en) | 1980-12-26 | 1980-12-26 | Butanediol derivative and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS57109742A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU681305B2 (en) * | 1994-07-18 | 1997-08-21 | University Of Queensland, The | Method and apparatus for separating liquid-liquid mixtures |
-
1980
- 1980-12-26 JP JP18614480A patent/JPS57109742A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57109742A (en) | 1982-07-08 |
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