JPH0240656B2 - - Google Patents
Info
- Publication number
- JPH0240656B2 JPH0240656B2 JP56186160A JP18616081A JPH0240656B2 JP H0240656 B2 JPH0240656 B2 JP H0240656B2 JP 56186160 A JP56186160 A JP 56186160A JP 18616081 A JP18616081 A JP 18616081A JP H0240656 B2 JPH0240656 B2 JP H0240656B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- oil
- ether
- abq
- dithiothreitol
- 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
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は一般式〔〕
〔式中、R1は―Ｃ（CH3）3を示し、R2およびR3は
同一かまたは異なつて、水素原子または２〜８個
の炭素原子を有する直鎖または分枝の低級アルカ
ノイル基を示す。〕で表わされる化合物に関する。
本発明化合物〔〕は白内障治療剤、抗菌剤、
抗腫瘍剤または肝機能改善剤として有用な化合物
である。すなわち、本発明の目的は価値ある薬理
的性質を有する化合物〔〕を提供するにある。
本発明化合物〔〕は列えば、一般式〔〕で
示される化合物
〔式中、R4は水素原子または２〜８個の炭素原
子を有する直鎖または分枝の低級アルカノイル基
を示す。〕と、一般式〔〕で示される化合物
R1COX 〔〕
〔式中、Ｘはヒドロキシ基、ハロゲン原子または
R1CO2―を示す。〕とをシヨツテンバウマン法、
混合酸無水物法などの公知のアシル化法により反
応させて合成することができる。本発明化合物
〔〕は２個またはそれ以上の不整炭素原子を有
するので立体異性体が存在する。これらはいずれ
も本発明の範囲に包含される。以下に実施例を示
す。
実施例 １
Ｓ，S′―ジピバロイルジチオスレイトールの製
造
脱気した10％炭酸ナトリウム水溶液41mlにジチ
オスレイトール2.0ｇを添加し、次いでエーテル
10mlを加えた後ピバロイルクロリド4.7ｇを氷冷
撹拌しながら滴下する。滴下終了後、氷冷下で３
時間撹拌を続け、エーテル100mlを加えて抽出す
る。エーテル層を飽和食塩水で洗浄し、無水硫酸
ナトリウムで乾燥後減圧濃縮して油状物4.5ｇを
得る。この油状物をシリカゲルカラムクロマトに
より精製して標記化合物4.1ｇ（98％）を得る。
融点 52〜54℃（ｎ―ヘキサン）
IR（neat，cm-1）：3430，3340，1670，1088，
1032，945，808，625
NMR（CDCl3，δ）：1.25（18H，ｓ，（ＣH3 ）
3CCO×２），2.62〜3.83（8H，ｍ，
The present invention is based on the general formula [] [In the formula, R 1 represents -C(CH 3 ) 3 , and R 2 and R 3 are the same or different and are a hydrogen atom or a straight-chain or branched lower alkanoyl group having 2 to 8 carbon atoms. shows. ]. The compound of the present invention [] is a cataract treatment agent, an antibacterial agent,
It is a compound useful as an antitumor agent or a liver function improving agent. That is, an object of the present invention is to provide a compound having valuable pharmacological properties. The compounds of the present invention [] are, for example, compounds represented by the general formula [] [In the formula, R 4 represents a hydrogen atom or a linear or branched lower alkanoyl group having 2 to 8 carbon atoms. ] and a compound represented by the general formula [] R 1 COX [] [wherein, X is a hydroxy group, a halogen atom, or
R 1 CO 2 - is shown. ] and Schotten Baumann method,
It can be synthesized by reaction using a known acylation method such as a mixed acid anhydride method. Since the compound of the present invention [ ] has two or more asymmetric carbon atoms, stereoisomers exist. All of these are included within the scope of the present invention. Examples are shown below. Example 1 Production of S,S'-dipivaloyl dithiothreitol 2.0 g of dithiothreitol was added to 41 ml of degassed 10% sodium carbonate aqueous solution, and then ether was added.
After adding 10 ml, 4.7 g of pivaloyl chloride was added dropwise while stirring on ice. After dropping, cool on ice for 3 minutes.
Continue stirring for an hour and add 100 ml of ether for extraction. The ether layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 4.5 g of an oil. This oil is purified by silica gel column chromatography to obtain 4.1 g (98%) of the title compound. Melting point 52-54℃ (n-hexane) IR (neat, cm -1 ): 3430, 3340, 1670, 1088,
1032,945,808,625 NMR (CDCl 3 , δ): 1.25 (18H, s, (CH 3 )
3 CCO×2), 2.62~3.83 (8H, m,
【式】）
実施例 ２
Ｏ，O′，Ｓ，S′―テトラピバロイルジチオスレ
イトールの製造
ジチオスレイトール1.0ｇをピリジン10mlに溶
解後、ピバロイルクロリド4.0ｇを氷冷撹拌しな
がら滴下する。滴下終了後、氷冷下で２時間、室
温で２時間撹拌した後、氷水中に注ぎ入れ、4N
硫酸で酸性とし、エーテルで抽出する。エーテル
層をNHCl、水、飽和重曹水、飽和食塩水の順に
洗浄し、無水硫酸ナトリウムで乾燥後減圧濃縮し
て油状物3.3ｇを得る。この油状物をシリカゲル
カラムクロマトにより精製後、減圧蒸留して標記
化合物2.7ｇ（85％）を得る。
沸点165〜175℃（1.0mmHg）
IR（neat，cm-1）：1740，1689，1482，1463，
1368，1279，1137，1035，950，810
NMR（CDCl3，δ）：１，23（63H，ｓ，（ＣH3 ）
3C―×４），2.98（2H，ABq（Ａ part）ｄ，
Ｊ＝7.5，13.5Hz，[Formula]) Example 2 Production of O,O',S,S'-tetrapivaloyl dithiothreitol After dissolving 1.0 g of dithiothreitol in 10 ml of pyridine, 4.0 g of pivaloyl chloride was added while stirring under ice cooling. Drip. After dropping, stir under ice cooling for 2 hours and at room temperature for 2 hours, then pour into ice water and add 4N
Acidify with sulfuric acid and extract with ether. The ether layer is washed with NHCl, water, saturated aqueous sodium bicarbonate, and saturated brine in this order, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 3.3 g of an oil. This oil was purified by silica gel column chromatography and then distilled under reduced pressure to obtain 2.7 g (85%) of the title compound. Boiling point 165-175℃ (1.0mmHg) IR (neat, cm -1 ): 1740, 1689, 1482, 1463,
1368, 1279, 1137, 1035, 950, 810 NMR (CDCl 3 , δ): 1, 23 (63H, s, (CH 3 )
3 C――×4), 2.98(2H, ABq(A part)d,
J=7.5, 13.5Hz,
【式】），
3.15（2H，ABq（Ｂ part）ｄ，Ｊ＝4.5，
13.5Hz，[Formula]), 3.15 (2H, ABq (B part) d, J=4.5,
13.5Hz,
【式】），５，12（2H， ｍ，[Formula]), 5, 12 (2H, m,
【式】）
実施例 ３
Ｏ，Ｓ，S′―トリピバロイルジチオスレイトー
ルの製造
ジチオスレイトール1.0ｇをピリジン10mlに溶
解後、ピバロイルクロリド2.8ｇを氷冷撹拌しな
がら滴下する。滴下終了後、氷冷下で４時間撹拌
した後、氷水中に注ぎ入れ、4N硫酸で酸性とし、
エーテルで抽出する。エーテル層をNHCl、水、
飽和重曹水、飽和食塩水の順に洗浄し、無水硫酸
ナトリウムで乾燥後減圧濃縮して油状物2.8ｇを
得る。この油状物をシリカゲルクロマトにより精
製して標記化合物1.9ｇ（72％）を得る。
IR（neat，cm-1）：3490，1735，1680，1478，
1458，1362，1278，1145，1033，950，806
NMR（CDCl3，δ）：1.23（27H，ｓ，（ＣH3 ）3C―
×３），2.70（1H，br ｓ，―ＯＨ），2.97
（2H，ｄ，Ｊ＝6.0Hz），―ＣH2 ―Ｓ―），
3.08（1H，ABq（Ａ part）ｄ，Ｊ＝7.5，
13.5Hz，[Formula]) Example 3 Production of O,S,S'-tripivaloyl dithiothreitol After dissolving 1.0 g of dithiothreitol in 10 ml of pyridine, 2.8 g of pivaloyl chloride was added dropwise while stirring under ice cooling. After dropping, stir under ice cooling for 4 hours, pour into ice water, acidify with 4N sulfuric acid,
Extract with ether. The ether layer was diluted with NHCl, water,
The mixture was washed with saturated sodium bicarbonate solution and saturated saline solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 2.8 g of an oily substance. This oil is purified by silica gel chromatography to yield 1.9 g (72%) of the title compound. IR (neat, cm -1 ): 3490, 1735, 1680, 1478,
1458, 1362, 1278, 1145, 1033, 950, 806 NMR (CDCl 3 , δ): 1.23 (27H, s, (CH 3 ) 3 C—
×3), 2.70 (1H, br s, -OH ), 2.97
(2H, d, J=6.0Hz), -C H 2 -S-),
3.08 (1H, ABq (A part) d, J=7.5,
13.5Hz,
【式】），3.25（1H，ABq
（Ｂ part）ｄ，Ｊ＝6.0，13.5Hz，
[Formula]), 3.25 (1H, ABq (B part) d, J=6.0, 13.5Hz,
【式】），3.77（1H，dt，Ｊ＝2.5， 6.0Hz，[Formula]), 3.77 (1H, dt, J=2.5, 6.0Hz,
【式】，4.90（1H，ddd，Ｊ＝ 2.5，6.0，7.5Hz，[Formula], 4.90 (1H, ddd, J= 2.5, 6.0, 7.5Hz,
【式】）
実施例 ４
Ｏ，O′―ジアセチル―Ｓ，S′―ジピバロイルジ
チオスレイトールの製造
実施例１で得られたＳ，S′―ジピバリルジチオ
スレイトール2.0ｇにピリジン10mlを加え、次い
で無水硫酸2.3mlを撹拌しながら加え、７時間撹
拌後氷水中に注ぎ入れてエーテルで抽出する。エ
ーテル層をNHCl、水、飽和重曹水、飽和食塩水
の順に洗浄し、無水硫酸ナトリウムで乾燥後減圧
濃縮して油状物2.6ｇを得る。この油状物を減圧
蒸留して標記化合物2.4ｇ（95％）得る。
沸点159〜167℃（0.9mmHg）
IR（neat，cm-1）：1750，1687，1482，1370，
1220，1033，951，810，625
NMR（CDCl3，δ）：1.22（18H，ｓ，（ＣH3 ）3C―
×２），2.07（6H，ｓ，ＣH3 CO―×２），
2.95（2H，ABq（Ａ part）ｄ，Ｊ＝7.5，
14.0Hz，[Formula]) Example 4 Production of O,O'-diacetyl-S,S'-dipivaloyldithiothreitol Pyridine was added to 2.0 g of S,S'-dipivalyldithiothreitol obtained in Example 1. Then, 2.3 ml of anhydrous sulfuric acid was added with stirring, and after stirring for 7 hours, the mixture was poured into ice water and extracted with ether. The ether layer is washed with NHCl, water, saturated aqueous sodium bicarbonate, and saturated brine in this order, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 2.6 g of an oil. Distillation of this oil under reduced pressure yields 2.4 g (95%) of the title compound. Boiling point 159-167℃ (0.9mmHg) IR (neat, cm -1 ): 1750, 1687, 1482, 1370,
1220, 1033, 951, 810, 625 NMR (CDCl 3 , δ): 1.22 (18H, s, (CH 3 ) 3 C—
×2), 2.07 (6H, s, C H 3 CO—×2),
2.95(2H, ABq(A part)d, J=7.5,
14.0Hz,
【式】），3.18（2H，
ABq（Ｂ part）ｄ，Ｊ＝6.0，14.0Hz，
[Formula]), 3.18 (2H, ABq (B part) d, J = 6.0, 14.0Hz,
【式】），5.10（2H，ｍ，[Formula]), 5.10 (2H, m,
【式】）【formula】)
Claims (1)
同一かまたは異なつて、水素原子または２〜８個
の炭素原子を有する直鎖または分枝の低級アルカ
ノイル基を示す。〕で表わされる化合物。[Claims] 1. General formula [In the formula, R 1 represents -C(CH 3 ) 3 , and R 2 and R 3 are the same or different and are a hydrogen atom or a straight-chain or branched lower alkanoyl group having 2 to 8 carbon atoms. shows. ] A compound represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56186160A JPS5888350A (en) | 1981-11-19 | 1981-11-19 | Acyldithioalditol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56186160A JPS5888350A (en) | 1981-11-19 | 1981-11-19 | Acyldithioalditol derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5888350A JPS5888350A (en) | 1983-05-26 |
| JPH0240656B2 true JPH0240656B2 (en) | 1990-09-12 |
Family
ID=16183427
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56186160A Granted JPS5888350A (en) | 1981-11-19 | 1981-11-19 | Acyldithioalditol derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5888350A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5686450A (en) * | 1995-06-07 | 1997-11-11 | Alcon Laboratories, Inc. | Use of N,N'-bis(mercaptoacetyl) hydrazine derivatives as anticataract agents |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5416591A (en) * | 1977-07-08 | 1979-02-07 | Kansai Paint Co Ltd | Photosensitive resin composition |
-
1981
- 1981-11-19 JP JP56186160A patent/JPS5888350A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5888350A (en) | 1983-05-26 |
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