JP3092865B2 - Method for producing optically active [3] (1,1 ') ferrocenophanes - Google Patents
Method for producing optically active [3] (1,1 ') ferrocenophanesInfo
- Publication number
- JP3092865B2 JP3092865B2 JP16002491A JP16002491A JP3092865B2 JP 3092865 B2 JP3092865 B2 JP 3092865B2 JP 16002491 A JP16002491 A JP 16002491A JP 16002491 A JP16002491 A JP 16002491A JP 3092865 B2 JP3092865 B2 JP 3092865B2
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- ferrocenophanes
- yeast
- ferrocenophane
- formyl
- 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 - Fee Related
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、一般式（ＩＩ）および
（ＩＩＩ）で示される光学活性な［３］（１，１’）フ
ェロセノファン類の製造方法に関するものである。光学
活性フェロセン類は、不斉還元金属錯体触媒の修飾に用
いられていることが知られている。(T.Hayashi, et. a
l.,Bull.Chem.Soc. Jpn.,53,1138(1980).)光学活性
［３］（１，１’）フェロセノファン類においても有機
金属錯体触媒の修飾剤としての同様な利用分野が考えら
れる。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a process for producing optically active [3] (1,1 ') ferrocenophanes represented by the general formulas (II) and (III). It is known that optically active ferrocenes are used for modifying an asymmetric reduced metal complex catalyst. (T. Hayashi, et.a
l., Bull. Chem. Soc. Jpn., 53 , 1138 (1980).) Optically active [3] (1,1 ') ferrocenophanes have similar fields of use as modifiers of organometallic complex catalysts. Can be considered.
【０００２】[0002]
【従来技術】光学活性［３］（１，１’）フェロセノフ
ァン類として知られているのは、５−および６−ヒドロ
キシメチル体、５−および６−カルボキシ体、５−およ
び６−ホルミル体などであるが、これらのものは、いず
れもラセミ体の光学分割により製造された光学活性５−
および６−カルボキシ［３］（１，１’）フェロセノフ
ァンを出発原料として化学的に合成されたもので、(H.F
alk, O.Hofer, K.Schoegl, Monatsch. Chem.,100,624
(1969).) パン酵母、リパーゼ、エステラーゼなどによ
る発酵法による製造方法はまだ知られていない。2. Description of the Related Art Optically active [3] (1,1 ') ferrocenophanes include 5- and 6-hydroxymethyl forms, 5- and 6-carboxy forms, 5- and 6-formyl groups. Optically active compounds produced by optical resolution of a racemic body.
And chemically synthesized from 6-carboxy [3] (1,1 ′) ferrocenophane as a starting material, wherein (HF
alk, O. Hofer, K. Schoegl, Monatsch. Chem., 100 , 624
(1969).) A production method by a fermentation method using baker's yeast, lipase, esterase, or the like is not yet known.
【０００３】[0003]
【発明が解決しようとする課題】従来の光学活性［３］
（１，１’）フェロセノファン類の製造方法は、ラセミ
体の光学分割という煩雑な方法によって製造されてきた
が、本発明は５−および６−ホルミル［３］（１，
１’）フェロセノファンのパン酵母による不斉還元反応
による、簡便な方法での光学活性［３］（１，１’）フ
ェロセノファン類の製造方法を提供するものである。SUMMARY OF THE INVENTION Conventional optical activity [3]
The method for producing (1,1 ′) ferrocenophanes has been produced by a complicated method of resolution of racemate, but the present invention relates to 5- and 6-formyl [3] (1,
1 ') It is intended to provide a method for producing optically active [3] (1,1') ferrocenophanes by a simple method by asymmetric reduction reaction of ferrocenophan with baker's yeast.
【０００４】[0004]
【課題を解決するための手段】すなわち本発明は、一般
式（Ｉ）で示されるラセミ体の［３］（１，１’）フェ
ロセノファン化合物をパン酵母の存在下還元することを
特徴とする光学活性ヒドロキシメチル［３］（１，
１’）フェロセノファン類（ＩＩ）および光学活性ホル
ミル［３］（１，１’）フェロセノファン類（ＩＩＩ）
の製造方法である。That is, the present invention is characterized in that a racemic [3] (1,1 ') ferrocenophane compound represented by the general formula (I) is reduced in the presence of baker's yeast. Optically active hydroxymethyl [3] (1,
1 ') Ferrocenophanes (II) and optically active formyl [3] (1,1') ferrocenophanes (III)
It is a manufacturing method of.
【化４】 （Ｉ）Embedded image (I)
【化５】 （ＩＩ）Embedded image (II)
【化６】 （ＩＩＩ）Embedded image (III)
【０００５】本発明で製造できる［３］（１，１’）フ
ェロセノファン類を具体的に例示すれば、（＋）−５−
ヒドロキシメチル［３］（１，１’）フェロセノファ
ン、（−）−５−ヒドロキシメチル［３］（１，１’）
フェロセノファン、（＋）−６−ヒドロキシメチル
［３］（１，１’）フェロセノファン、（−）−６−ヒ
ドロキシメチル［３］（１，１’）フェロセノファン、
（＋）−５−ホルミル［３］（１，１’）フェロセノフ
ァン、（−）−５−ホルミル［３］（１，１’）フェロ
セノファン、（＋）−６−ホルミル［３］（１，１’）
フェロセノファン、（−）−６−ホルミル［３］（１，
１’）フェロセノファン、などが挙げられる。The [3] (1,1 ') ferrocenophanes that can be produced by the present invention are specifically exemplified by (+)-5-
Hydroxymethyl [3] (1,1 ′) ferrosenophane, (−)-5-hydroxymethyl [3] (1,1 ′)
Ferrocenophane, (+)-6-hydroxymethyl [3] (1,1 ′) ferrocenophane, (−)-6-hydroxymethyl [3] (1,1 ′) ferrocenophane,
(+)-5-formyl [3] (1,1 ′) ferrosenophane, (−)-5-formyl [3] (1,1 ′) ferrosenophane, (+)-6-formyl [3] (1,1 ')
Ferrocenophane, (−)-6-formyl [3] (1,
1 ′) ferrosenophane, and the like.
【０００６】本発明の出発原料となる一般式（Ｉ）のラ
セミ体の５−または６−ホルミル［３］（１，１’）フ
ェロセノファン類は、既に公知の方法で製造できる。
(H.Falk, O.Hofer, K.Schoegl, Monatsch. Chem.,100,6
24 (1969).) すなわち、［３］（１，１’）フェロセノ
ファンにフリーデルクラフツ反応でＮ，Ｎ−ジフェニル
カルバミルクロライドを反応させて、５−および６−カ
ルボキシ［３］（１，１’）フェロセノファンとし、更
にエステル化を行い５−および６−アルコキシカルボニ
ル［３］（１，１’）フェロセノファンとした後、水素
化アルミニウムリチウムで還元、更に活性二酸化マンガ
ンで酸化させることにより５−および６−ホルミル
［３］（１，１’）フェロセノファンを容易に製造する
ことができる。The racemic 5- or 6-formyl [3] (1,1 ′) ferrocenophanes of the general formula (I), which are starting materials of the present invention, can be produced by a known method.
(H. Falk, O. Hofer, K. Schoegl, Monatsch. Chem., 100 , 6
24 (1969).) That is, [3] (1,1 ′) ferrocenophane was reacted with N, N-diphenylcarbamyl chloride by a Friedel Crafts reaction to give 5- and 6-carboxy [3] (1 , 1 ') ferrocenophane, followed by esterification to give 5- and 6-alkoxycarbonyl [3] (1,1') ferrocenophane, reduction with lithium aluminum hydride and further oxidation with active manganese dioxide By doing so, 5- and 6-formyl [3] (1,1 ′) ferrosenophane can be easily produced.
【０００７】本発明で使用されるパン酵母は、市販のプ
レスしたパン酵母、乾燥したパン酵母のいずれでも使用
可能であり、高分子化合物に固定した固定化パン酵母も
使用できる。反応は、通常水溶媒中で行われるが、固定
化パン酵母を利用する場合には、溶媒として、エタノー
ル、イソプロパノール等の低級アルコール類、トルエ
ン、ヘキサン等の炭化水素系溶媒も使用できる。溶媒の
使用量は、原料に対して０．２５ないし１０倍程度が良
い。溶液のｐＨは、パン酵母の活性が引き出せる５．５
ないし７．５の範囲に調整するのが望ましい。パン酵母
のエネルギー源として、エタノール、グルコース、およ
びスクロースなどの糖類を添加することが好ましい。反
応温度は１０〜５０℃の範囲で行われ、特に室温〜４０
℃の範囲で反応するのが良い。As the baker's yeast used in the present invention, any of a commercially available pressed baker's yeast and dried baker's yeast can be used, and an immobilized baker's yeast fixed to a polymer compound can also be used. The reaction is usually performed in an aqueous solvent, but when immobilized baker's yeast is used, lower alcohols such as ethanol and isopropanol, and hydrocarbon solvents such as toluene and hexane can be used as the solvent. The amount of the solvent used is preferably about 0.25 to 10 times the raw material. The pH of the solution is 5.5 at which the activity of baker's yeast can be extracted.
It is desirable to adjust the range to 7.5. It is preferable to add sugars such as ethanol, glucose, and sucrose as energy sources for baker's yeast. The reaction is carried out at a temperature in the range of 10 to 50 ° C., in particular, room temperature to 40 ° C.
It is good to react in the range of ° C.
【０００８】本発明の一実施態様を述べれば、最初にグ
ルコースの水溶液にパン酵母を懸濁して発酵させてお
き、これに出発原料（Ｉ）のエタノール溶液を徐々に滴
下して反応させる方法がある。反応は、出発原料、パン
酵母の状態によっても異なるが、数時間ないし１０数時
間程度で終了する。反応終了後は、菌体を濾別し、溶媒
を除去した後、カラムクロマトグラフィーなどで精製す
れば、目的物の光学活性アルコール類（ＩＩ）、光学活
性アルデヒド類（ＩＩＩ）を得ることができる。According to one embodiment of the present invention, there is a method in which baker's yeast is first suspended in an aqueous solution of glucose for fermentation, and an ethanol solution of the starting material (I) is gradually added dropwise to react. is there. The reaction is completed in about several hours to about ten and several hours, depending on the starting materials and the state of baker's yeast. After completion of the reaction, the cells are removed by filtration, the solvent is removed, and the mixture is purified by column chromatography or the like, whereby the desired optically active alcohols (II) and optically active aldehydes (III) can be obtained. .
【０００９】このようなパン酵母によるアルデヒド化合
物（Ｉ）の不斉還元反応により、原料のラセミ体（Ｉ）
のいずれか一方の光化学活性体が選択的に還元されて、
光学活性なアルコール体（ＩＩ）が還元生成体として生
成し、原料化合物のうちの他の一方の光学活性体である
アルデヒド（ＩＩＩ）が還元残として残り、結局二種の
光学活性な化合物が同時に得られる。また、得られた還
元残であるアルデヒド体（ＩＩＩ）を水素化ホウ素ナト
リウムなどによる化学還元により、先に得られた光学活
性アルコール（ＩＩ）とは反対の立体配置を有する光学
活性アルコールに導くことができる。また、還元生成体
（ＩＩ）を活性二酸化マンガンで酸化すると、還元残と
して得られたアルデヒド体（ＩＩＩ）とは反対の立体配
置を有する光学活性アルデヒドに容易に導くことができ
る。The asymmetric reduction reaction of the aldehyde compound (I) by such a baker's yeast produces the racemic (I) starting material.
One of the photochemically active is selectively reduced,
The optically active alcohol compound (II) is produced as a reduction product, and the other optically active compound, aldehyde (III), is left as a reduction residue, so that two optically active compounds are simultaneously obtained. can get. Further, the obtained aldehyde derivative (III) as a reduction residue is converted to an optically active alcohol having a configuration opposite to that of the previously obtained optically active alcohol (II) by chemical reduction with sodium borohydride or the like. Can be. Further, when the reduction product (II) is oxidized with active manganese dioxide, it can be easily led to an optically active aldehyde having a configuration opposite to that of the aldehyde compound (III) obtained as a residual residue.
【００１０】以下、実施例により本発明を更に詳細に説
明する。Hereinafter, the present invention will be described in more detail with reference to examples.
実施例１５−ホルミル［３］（１，１’）フェロセノファンのパ
ン酵母による還元 Ｄ−グルコース４５ｇを蒸留水５７０ｍｌに溶かし、３
０℃で攪拌しながら乾燥パン酵母（オリエンタル酵母工
業（株）製）４５ｇを少しずつ加え２０分間温度を保ち
ながら攪拌を続け発酵させた。５−ホルミル［３］
（１，１’）フェロセノファン５７０ｍｇをエタノール
１０ｍｌに溶かした溶液を滴下し、３０℃で１時間攪拌
した。エーテル１２０ｍｌを加え反応を停止させ、濾過
した後、濾液をエーテル抽出した。抽出液を脱水後、エ
ーテルを留去し、残液はヘキサン・エーテル（５：１）
を溶離液とし、シリカゲルカラムを用いたカラムクロマ
トグラフ法により精製した。第一溶出液より（−）−
（４Ｒ，５Ｓ）−５−ホルミル［３］（１，１’）フェ
ロセノファン｛暗橙色オイル、〔α〕D 20 ３８．１°、
収率３７％｝を得た。第二溶出液より（＋）−（４Ｓ，
５Ｒ）−５−ヒドロキシメチル［３］（１，１’）フェ
ロセノファン｛黄色結晶、ｍｐ７１〜７４℃、〔α〕D
20 ＋２４．７°（文献値〔α〕D 20 ＋３４°）、ｅｅ
７３％｝を得た。 実施例２６−ホルミル［３］（１，１’）フェロセノファンのパ
ン酵母による還元 ６−ホルミル［３］（１，１’）フェロセノファン５０
０ｍｇを出発原料とし、他の条件は実施例１の場合と同
様にして反応し（ただし反応時間は２時間）、（−）−
（４Ｓ，６Ｒ）−６−ホルミル［３］（１，１’）フェ
ロセノファン｛橙色結晶、ｍｐ７２〜７９℃、〔α〕D
20 −２９５°（文献値〔α〕D 20 −３６０°）、ｅｅ
８２％、収率２０．７％｝および（−）−（４Ｒ，６
Ｓ）−６−ヒドロキシメチル［３］（１，１’）フェロ
セノファン｛橙色オイル、〔α〕D 20−３０．０°、収
率１３％｝を得た。Example 1 5-formyl [3] (1,1 ′) ferrocenophane
Dissolve 45 g of reduced D-glucose by yeast in 570 ml of distilled water.
While stirring at 0 ° C., 45 g of dry baker's yeast (manufactured by Oriental Yeast Co., Ltd.) was added little by little, and stirring was continued while maintaining the temperature for 20 minutes to ferment. 5-formyl [3]
A solution of 570 mg of (1,1 ′) ferrocenophane dissolved in 10 ml of ethanol was added dropwise, and the mixture was stirred at 30 ° C. for 1 hour. After adding 120 ml of ether to stop the reaction and filtering, the filtrate was extracted with ether. After the extract was dehydrated, ether was distilled off, and the remaining liquid was hexane / ether (5: 1).
Was used as an eluent and purified by column chromatography using a silica gel column. From the first eluate (-)-
(4R, 5S) -5-formyl [3] (1,1 ′) ferrocenophane dark orange oil, [α] D 20 38.1 °,
A yield of 37% was obtained. From the second eluate (+)-(4S,
5R) -5-Hydroxymethyl [3] (1,1 ′) ferrosenophane yellow crystal, mp 71-74 ° C., [α] D
20 + 24.7 ° (literature value [α] D 20 + 34 °), ee
73%｝ was obtained. Example 2 6-Formyl [3] (1,1 ') Ferrocenophane
Reduction by emission Yeast 6-formyl [3] (1,1 ') Ferro Seno fan 50
Using 0 mg as a starting material, the reaction was carried out in the same manner as in Example 1 except that the reaction time was 2 hours, and (-)-
(4S, 6R) -6-formyl [3] (1,1 ′) ferrocenophane orange crystal, mp 72-79 ° C., [α] D
20 -295 ° (literature value [α] D 20 -360 °), ee
82%, yield 20.7%} and (-)-(4R, 6
S) -6-Hydroxymethyl [3] (1,1 ′) ferrocenophane (orange oil, [α] D 20 -30.0 °, yield 13%) was obtained.
【発明の効果】本発明により、ラセミ体の［３］（１，
１’）フェロセノファン化合物の一方の光学活性体を選
択的に還元することができ、得られた還元生成物と還元
残とを分離することによって、二種類の光学活性体を得
ることができる。According to the present invention, the racemic [3] (1,
1 ′) One optically active form of the ferrocenophane compound can be selectively reduced, and two types of optically active forms can be obtained by separating the obtained reduction product and the reduction residue. .
───────────────────────────────────────────────────── フロントページの続き (58)調査した分野(Int.Cl.7，ＤＢ名) C12P 41/00 C07F 17/02 ＢＩＯＳＩＳ（ＤＩＡＬＯＧ) ＣＡ（ＳＴＮ)──────────────────────────────────────────────────続 き Continued on the front page (58) Fields surveyed (Int. Cl. 7 , DB name) C12P 41/00 C07F 17/02 BIOSIS (DIALOG) CA (STN)
Claims (1)
の［３］（１，１’）フェロセノファン化合物をパン酵
母の存在下還元することを特徴とする光学活性ヒドロキ
シメチル［３］（１，１’）フェロセノファン類（Ｉ
Ｉ）および光学活性ホルミル［３］（１，１’）フェロ
セノファン類（ＩＩＩ）の製造方法。 【化１】 （Ｉ） 【化２】 （ＩＩ） 【化３】 （ＩＩＩ）1. An optically active hydroxymethyl [3] characterized by reducing a racemic [3] (1,1 ′) ferrocenophane compound represented by the following general formula (I) in the presence of baker's yeast. (1,1 ′) ferrocenophanes (I
Processes for producing I) and optically active formyl [3] (1,1 ′) ferrocenophanes (III). Embedded image (I) (II) (III)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16002491A JP3092865B2 (en) | 1991-06-03 | 1991-06-03 | Method for producing optically active [3] (1,1 ') ferrocenophanes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16002491A JP3092865B2 (en) | 1991-06-03 | 1991-06-03 | Method for producing optically active [3] (1,1 ') ferrocenophanes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0866195A JPH0866195A (en) | 1996-03-12 |
| JP3092865B2 true JP3092865B2 (en) | 2000-09-25 |
Family
ID=15706319
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16002491A Expired - Fee Related JP3092865B2 (en) | 1991-06-03 | 1991-06-03 | Method for producing optically active [3] (1,1 ') ferrocenophanes |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3092865B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0801195D0 (en) * | 2008-01-23 | 2008-02-27 | Acal Energy Ltd | Fuel cells |
-
1991
- 1991-06-03 JP JP16002491A patent/JP3092865B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0866195A (en) | 1996-03-12 |
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