JP2869745B2 - Optically active dichlorlactone compound, method for producing the same, and method for producing optically active diol compound using the same - Google Patents
Optically active dichlorlactone compound, method for producing the same, and method for producing optically active diol compound using the sameInfo
- Publication number
- JP2869745B2 JP2869745B2 JP14502190A JP14502190A JP2869745B2 JP 2869745 B2 JP2869745 B2 JP 2869745B2 JP 14502190 A JP14502190 A JP 14502190A JP 14502190 A JP14502190 A JP 14502190A JP 2869745 B2 JP2869745 B2 JP 2869745B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- optically active
- producing
- compound
- compound represented
- 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
- -1 diol compound Chemical class 0.000 title claims description 32
- 150000001875 compounds Chemical class 0.000 title claims description 18
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 10
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 235000019270 ammonium chloride Nutrition 0.000 claims description 5
- 238000006298 dechlorination reaction Methods 0.000 claims description 5
- 238000003381 deacetylation reaction Methods 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 150000001721 carbon Chemical class 0.000 claims description 3
- 150000002596 lactones Chemical class 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000000203 mixture Substances 0.000 description 8
- RHLVCLIPMVJYKS-UHFFFAOYSA-N 3-octanone Chemical compound CCCCCC(=O)CC RHLVCLIPMVJYKS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 3
- 150000003180 prostaglandins Chemical class 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- JTAUWJLJUCDEEZ-UHNVWZDZSA-N (3aR,6aS)-3,3-dichloro-6,6a-dihydro-3aH-cyclopenta[b]furan-2-one Chemical compound ClC1(C(O[C@H]2CC=C[C@@H]12)=O)Cl JTAUWJLJUCDEEZ-UHNVWZDZSA-N 0.000 description 1
- VYTZWRCSPHQSFX-UCROKIRRSA-N (3ar,4r,5r,6as)-5-hydroxy-4-(hydroxymethyl)-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one Chemical compound O1C(=O)C[C@@H]2[C@H](CO)[C@H](O)C[C@@H]21 VYTZWRCSPHQSFX-UCROKIRRSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- HKRINOUVJKXKIQ-UHFFFAOYSA-N 5-hydroxy-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one Chemical compound C1C(=O)OC2CC(O)CC21 HKRINOUVJKXKIQ-UHFFFAOYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- NUECNIRLVVHOFP-DOLQZWNJSA-N O1C(=O)C(Cl)(Cl)[C@@H]2[C@H](COC(=O)C)[C@H](OC(C)=O)C[C@@H]21 Chemical compound O1C(=O)C(Cl)(Cl)[C@@H]2[C@H](COC(=O)C)[C@H](OC(C)=O)C[C@@H]21 NUECNIRLVVHOFP-DOLQZWNJSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000005657 iodolactonization reaction Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明はプロスタグランジン類の製造において重要な
合成中間体に関する。Description: TECHNICAL FIELD The present invention relates to a synthetic intermediate which is important in the production of prostaglandins.
（従来技術） プロスタグランジン類の重要な合成中間体である式 で表される光学活性ラクトンジオール化合物の合成法に
関しては多くの報告がなされている。E.J.Coreyはシク
ロペンタジエンよりディールス・アルダー反応、ヨード
ラクトン化反応などを用いてラクトンジオール類を合成
している。（J.Am.Chem.Soc.,93,1491,1971）I.Tｍ
skziらは、シクロペンタジエンより４行程で合成され
る式 で表されるラクトン化合物にプリンス反応を施すことに
よって式 で表されるラクトンジアセテート化合物とし、次いでこ
れを加水分解することにより合成している。（Tetrahed
ron Left.,4639〜4642,1976） （発明が解決しようとする問題点） E.J.Coreyらの方法は行程が長く、使用されている試
薬も工業的に不利なものが多い。I.Tｍskziらの
合成方法では、ラクトン化合物［式IV］にプリンス反応
を施してラクトンジアセテート化合物［式Ｖ］を得るに
際し、シリカゲルカラムクロマトグラフィーを用いた精
製を行っている。工業的製造において、シリカゲルクロ
マトグラフィーによる精製は操作的にも価格的にも非常
に不利である。(Prior Art) Formulas that are important synthetic intermediates of prostaglandins Many reports have been made on a method for synthesizing an optically active lactone diol compound represented by the formula: EJCorey synthesizes lactone diols from cyclopentadiene using Diels-Alder reaction and iodolactonization reaction. (J. Am. Chem. Soc., 93,1491,1971) I. Tm
skzi et al. formulas synthesized in four steps from cyclopentadiene By subjecting the lactone compound represented by The lactone diacetate compound represented by the formula is then synthesized by hydrolysis. (Tetrahed
ron Left., 4639-4642, 1976) (Problems to be Solved by the Invention) The method of EJCorey et al. is a long process, and many of the reagents used are industrially disadvantageous. In the synthesis method of I. Tmskzi et al., When a lactone compound [formula IV] is subjected to a Prince reaction to obtain a lactone diacetate compound [formula V], purification is performed using silica gel column chromatography. In industrial production, purification by silica gel chromatography is very disadvantageous both in terms of operation and cost.
（問題を解決する為の方法） 本発明者からはかかる欠点を克服すべく鋭意研究した
結果、新規なジクロルラクトン化合物［式Ｉ］を経由す
る光学活性ラクトンジオール化合物［式III］の簡便な
製造方法を発明するに至った。チャート１に本発明の概
要を示す。(Method for Solving the Problems) As a result of intensive studies from the present inventors to overcome such drawbacks, the present inventors have found that a simple dichlorolactone compound [formula I] can be used to easily produce an optically active lactone diol compound [formula III]. We have invented a manufacturing method. Chart 1 shows an outline of the present invention.
すなわち本発明においては、まず公知の光学活性ラクト
ン化合物［式II］（日特開 昭58−103381、昭58−1033
82）を無水酢酸を添加したプリンス反応を施すことによ
って、新規なジクロルラクトンジアセテート化合物［式
I a］を得る。次にこれをメタノール溶媒中にて塩化ア
ンモニウム存在下、亜鉛末で脱クロル化反応及び脱アセ
チル化反応させることにより目的とするラクトンジオー
ル化合物［式III］を簡便にすることが出来る。ラクト
ンジオール化合物［式III］は、ジクロルラクトンアセ
テート化合物［式I a］を加水分解して新規なジクロル
ラクトンジオール化合物［式I b］とした後、亜鉛末に
よる脱クロル化反応を行うことにより得ることも出来
る。新規なジクロルラクトンジアセテート化合物［式I
a］及びジクロルラクトンジオール化合物［式I b］は結
晶性に優れ、再結晶法による効率良い精製が可能であ
る。すなわち、プリンス反応後の精製は工業的に不利な
シリカゲルクロマトグラフィーを行わずとも、ルートａ
においてはジクロルラクトンジアセテート化合物［式I
a］の再結晶により、ルートｂにおいてはジクロルラク
トンジオール化合物［式I b］の再結晶により行うこと
が出来るのである。また、ルートａによればラクトン化
合物［式II］より実質２行程で目的とするラクトンジオ
ール化合物［式III］を得ることが出来る。 That is, in the present invention, first, a known optically active lactone compound [formula II] (Japanese Patent Application Laid-Open Nos. 58-103381 and 58-1033)
82) is subjected to a Prince reaction with the addition of acetic anhydride to give a novel dichlorolactone diacetate compound [formula
Ia]. Then, this is subjected to a dechlorination reaction and a deacetylation reaction with zinc powder in the presence of ammonium chloride in a methanol solvent, whereby the desired lactone diol compound [formula III] can be simplified. The lactone diol compound [formula III] is obtained by hydrolyzing a dichlorlactone acetate compound [formula Ia] to obtain a novel dichlorolactone diol compound [formula Ib], and then performing a dechlorination reaction with zinc powder. Can also be obtained. New dichlorlactone diacetate compounds [Formula I
a] and the dichlorolactone diol compound [formula Ib] have excellent crystallinity and can be efficiently purified by a recrystallization method. That is, the purification after the Prince reaction can be carried out without performing industrially disadvantageous silica gel chromatography, without using route a.
In the above, a dichlorolactone diacetate compound [formula I
By the recrystallization of a), the route b can be carried out by recrystallization of the dichlorolactone diol compound [formula Ib]. According to route a, the target lactone diol compound [formula III] can be obtained in substantially two steps from the lactone compound [formula II].
以下に本発明を詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明においては、まずラクトン化合物［式II］をプ
リンス反応によってジクロルラクトンジアセテート化合
物［式I a］に変換する。この反応はハロゲン化炭素溶
媒中、強酸と無水酢酸の存在下、ホルムアルデヒド重合
体を50〜60℃に加熱することにより解重合させた後、ラ
クトン化合物［式II］を加え、50〜80℃で24〜72時間行
うものである。ハロゲン化炭素溶媒としてはクロロホル
ム、1,2−ジクロルエタンが好ましい。強酸としては濃
硫酸、三フッ化ホウ素エーテル錯体が好ましい。反応終
了後は通常の後処理を行い、酢酸エチル−ヘキサンある
いはイソプロピルアルコール−ヘキサンの混合溶媒で再
結晶することにより、ジクロルラクトンジアセテート化
合物［式I a］を収率良く得ることが出来る。この反応
においては、無水酢酸の添加は必須であり、無水酢酸を
添加しないと収率は極度に低下する。チャート１のルー
トａにしたがって製造を行う場合、再結晶により精製し
たジクロルラクトンジアセテート化合物［式I a］を５
〜10倍容量のメタノール、１〜３倍モルの塩化アンモニ
ウム、３〜５倍モルの亜鉛末からなる加熱還流した混合
物中に滴下し、その後３〜５時間反応させることで行わ
れる。通常の後処理を行い、ラクトンジオール化合物
［式III］が定量的収率で得られる。ルートｂに従って
製造を行う場合、ジクロルラクトンジアセテート化合物
［式I a］の再結晶は行わずにプリンス反応によって得
られた粗生成物をメタノール、エタノールなどのアルコ
ール溶媒に溶解し、希塩酸または希硫酸を加えて加熱還
流することにより脱アセチル化反応を行う。通常の後処
理行い、クロロホルムで再結晶することによりジクロル
ラクトンジオール化合物［式I b］を収率良く得ること
が出来る。つづく脱クロル化反応は、ジクロルラクトン
ジアセテート化合物［式I a］の脱クロル化反応と同様
に行うことが出来、ラクトンジオール化合物［式III］
が定量的収率で得られる。In the present invention, first, a lactone compound [formula II] is converted to a dichlorlactone diacetate compound [formula Ia] by a Prince reaction. This reaction is carried out in a halogenated carbon solvent in the presence of a strong acid and acetic anhydride by depolymerizing the formaldehyde polymer by heating to 50 to 60 ° C, adding the lactone compound [Formula II], and adding the lactone compound at 50 to 80 ° C. 24 to 72 hours. Chloroform and 1,2-dichloroethane are preferred as the halogenated carbon solvent. As the strong acid, concentrated sulfuric acid and boron trifluoride etherate are preferable. After completion of the reaction, ordinary post-treatment is carried out, and recrystallization is performed with a mixed solvent of ethyl acetate-hexane or isopropyl alcohol-hexane, whereby a dichlorolactone diacetate compound [formula Ia] can be obtained in a high yield. In this reaction, the addition of acetic anhydride is essential, and without acetic anhydride, the yield is extremely reduced. When the production is carried out in accordance with the route a of Chart 1, the dichloractone diacetate compound [formula Ia] purified by recrystallization is treated with 5
The reaction is carried out by dropping into a heated and refluxed mixture consisting of 1010 times the volume of methanol, 1 to 3 times the amount of ammonium chloride, and 3 to 5 times the volume of zinc dust, and then reacting for 3 to 5 hours. The usual post-treatment gives the lactone diol compound [formula III] in quantitative yield. When the production is carried out according to route b, the crude product obtained by the Prince reaction without recrystallization of the dichloractone diacetate compound [formula Ia] is dissolved in an alcohol solvent such as methanol or ethanol, and diluted hydrochloric acid or dilute hydrochloric acid. A deacetylation reaction is performed by adding sulfuric acid and heating to reflux. By performing a usual post-treatment and recrystallizing with chloroform, a dichlorolactone diol compound [formula Ib] can be obtained in good yield. The subsequent dechlorination reaction can be carried out in the same manner as the dechlorination reaction of the dichlorolactone diacetate compound [formula Ia], and the lactone diol compound [formula III]
Is obtained in quantitative yield.
以上、本発明は、公知の光学活性ラクトン化合物［式
II］より、新規なジクロルラクトンジアセテート化合物
［式I a］、ジクロルラクトンジオール化合物［式I b］
を合成し、これらよりプロスタグランジン類合成上の重
要な中間体であるラクトンジオール化合物［式III］を
合成する工業的に有利な製造法である。As described above, the present invention relates to a known optically active lactone compound [formula
II], a novel dichlorolactone diacetate compound [formula Ia], a dichlorlactone diol compound [formula Ib]
And a lactone diol compound [formula III], which is an important intermediate in the synthesis of prostaglandins, is industrially advantageous from these.
（発明の効果） 本発明によれば、既知のラクトン化合物［式II］より
ラクトンジオール化合物［式III］をシリカゲルカラム
クロマト精製を行うことなく収率良く得ることができ
る。(Effect of the Invention) According to the present invention, a lactone diol compound [formula III] can be obtained from a known lactone compound [formula II] in good yield without performing silica gel column chromatography purification.
以下に、実施例を挙げて本発明を更に詳細に説明する
が、本発明はこれらによりなんら制限されるものではな
い。Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.
実施例 １ クロロホルム120ml、パラホルムアルデヒド22.1g、無
水酢酸60mlからなる混合物中に濃硫酸42mlを滴下する。
50−60℃でパラホルムアルデヒドを解重合させた後、
（1S,5R）−4,4−ジクロル−２−オキサビシクロ［3,3,
0］オクト−６−エン−３−オン19.3gを加え、60℃で48
時間撹拌する。反応液を室温まで冷却した後、ブライン
300mlで希釈する。分液し、水層はクロロホルム100mlで
二回抽出する。クロロホルム層を合せ、飽和炭酸水素ナ
トリウム水溶液で洗浄する。無水硫酸マグネシウムで乾
燥した後、濃縮し、残留物をイソプロピルアルコール80
mlに溶解する。氷冷後、白濁するまでヘキサンを加え、
５℃で24時間撹拌する。結晶を濾取乾燥して（1S,5R,6
R,7R）−4,4−ジクロル−６−アセトキシメチル−７−
アセトキシ−２−オキサビシクロ［3,3,0］オクタン−
３−オン21.1gを得る。Example 1 42 ml of concentrated sulfuric acid is added dropwise to a mixture of 120 ml of chloroform, 22.1 g of paraformaldehyde and 60 ml of acetic anhydride.
After depolymerizing paraformaldehyde at 50-60 ° C,
(1S, 5R) -4,4-dichloro-2-oxabicyclo [3,3,
0] Oct-6-en-3-one (19.3 g)
Stir for hours. After cooling the reaction to room temperature, brine
Dilute with 300ml. Separate, and extract the aqueous layer twice with 100 ml of chloroform. Combine the chloroform layers and wash with saturated aqueous sodium bicarbonate. After drying over anhydrous magnesium sulfate, the mixture was concentrated, and the residue was treated with isopropyl alcohol 80
Dissolve in ml. After cooling with ice, add hexane until cloudy,
Stir at 5 ° C. for 24 hours. The crystals are collected by filtration and dried (1S, 5R, 6
(R, 7R) -4,4-dichloro-6-acetoxymethyl-7-
Acetoxy-2-oxabicyclo [3,3,0] octane-
21.1 g of 3-one are obtained.
融点:65−66℃ ▲［α］20 D▼＝−62.1゜（ｃ＝1.0クロロホルム）1 H NMR（90MHz,CDCl3）：δ＝2.03（s,3H）,2.14（s,3
H）,2.37（q,J＝5.1Hz,2H）,2.60（m,1H）,3.30（t.J＝
5.1Hz,1H）,4.26（d,J＝5.1Hz,2H）,5.21（m,2H）． IR（KBr）:1795,1740,1380,1240,1170,1060,1040,960,8
30,720. 実施例 ２ （1S,5R,6R,7R）−4,4−ジクロル−６−アセトキシメ
チル−７−アセトキシ−２−オキサビシクロ［3,3,0］
オクタン−３−オン14gをメタノール200mlに溶解する。
これに濃塩酸4mlを加え、３時間加熱還流を行う。反応
終了後、氷冷下に飽和炭酸水素ナトリウム水溶液を加え
て中和し、濃縮する。残分をクロロホルムに加熱溶解
し、熱時に濾過する。濾液を氷冷し、析出した結晶を濾
取乾燥して（1S,5R,6R,7R）−4,4−ジクロル−６−ヒド
ロキシメチル−７−ヒドロキシ−２−オキサビシクロ
［3,3,0］オクタン−３−オン7.8gを得る。Melting point: 65-66 ° C ▲ [α] 20 D ▼ = -62.1 ゜ (c = 1.0 chloroform) 1 H NMR (90 MHz, CDCl 3 ): δ = 2.03 (s, 3H), 2.14 (s, 3)
H), 2.37 (q, J = 5.1 Hz, 2H), 2.60 (m, 1H), 3.30 (tJ =
5.1Hz, 1H), 4.26 (d, J = 5.1Hz, 2H), 5.21 (m, 2H). IR (KBr): 1795,1740,1380,1240,1170,1060,1040,960,8
30,720. Example 2 (1S, 5R, 6R, 7R) -4,4-dichloro-6-acetoxymethyl-7-acetoxy-2-oxabicyclo [3,3,0]
Dissolve 14 g of octane-3-one in 200 ml of methanol.
4 ml of concentrated hydrochloric acid is added thereto, and the mixture is heated under reflux for 3 hours. After completion of the reaction, the mixture is neutralized by adding a saturated aqueous solution of sodium hydrogen carbonate under ice cooling, and concentrated. The residue is heated and dissolved in chloroform and filtered while hot. The filtrate was cooled on ice, and the precipitated crystals were collected by filtration and dried to give (1S, 5R, 6R, 7R) -4,4-dichloro-6-hydroxymethyl-7-hydroxy-2-oxabicyclo [3,3,0 7.8 g of octane-3-one are obtained.
▲［α］20 D▼＝−52.9゜（ｃ＝1.0メタノール） 融点:102−103℃1 H NMR（90MHz,D2O）：δ＝2.27（t,J＝4.3Hz,2H）,2.9
0（t,J＝8.0Hz,1H）,3.46（t,J＝5.5Hz,1H）,3.64（d,J
＝6.5Hz,2H）,4.28（q,J＝3.8Hz,1H）,5.38（m,1H）． IR（KBr）:3260,1780,1210,1170,1030,960,840,720. 実施例 ３ 加熱還流したメタノール30ml、塩化アンモニウム、2.
0g、亜鉛末6.5gからなる混合物中に、メタノール20mlに
溶解した（1S,5R,6R,7R）−4,4−ジクロル−６−ヒドロ
キシメチル−７−ヒドロキシ−２−オキサビシクロ［3,
3,0］オクタン−３−オン7.7gを激しく撹拌しながら滴
下する。その後３時間撹拌、加熱還流を行う。室温まで
冷却後、濾過を行い、濾液を濃縮する。残留物を塩化メ
チレン300mlに加熱溶解し、さらに濾過を行う。▲ [α] 20 D ▼ = -52.9 ゜ (c = 1.0 methanol) Melting point: 102-103 ° C. 1 H NMR (90 MHz, D 2 O): δ = 2.27 (t, J = 4.3 Hz, 2H), 2.9
0 (t, J = 8.0 Hz, 1H), 3.46 (t, J = 5.5 Hz, 1H), 3.64 (d, J
= 6.5Hz, 2H), 4.28 (q, J = 3.8Hz, 1H), 5.38 (m, 1H). IR (KBr): 3260, 1780, 1210, 1170, 1030, 960, 840, 720. Example 3 30 ml of methanol refluxed under heating, ammonium chloride, 2.
In a mixture consisting of 0 g and zinc powder 6.5 g, (1S, 5R, 6R, 7R) -4,4-dichloro-6-hydroxymethyl-7-hydroxy-2-oxabicyclo [3,
3,0] Octane-3-one (7.7 g) is added dropwise with vigorous stirring. Thereafter, the mixture is stirred and heated under reflux for 3 hours. After cooling to room temperature, filtration is performed, and the filtrate is concentrated. The residue is heated and dissolved in 300 ml of methylene chloride and filtered.
濾液を濃縮して（1S,5R,6R,7R）−６−ヒドロキシメ
チル−７−ヒドロキシ−２−オキサビシクロ［3,3,0］
オクタン−３−オン5.3gを得る。The filtrate is concentrated and (1S, 5R, 6R, 7R) -6-hydroxymethyl-7-hydroxy-2-oxabicyclo [3,3,0]
5.3 g of octane-3-one are obtained.
融点:102−104℃ ▲［α］20 D▼＝−45.0゜（ｃ＝1.0メタノール）1 H NMR（90MHz,D2O）：δ＝2.06（d,J＝4.5Hz,2H）,2.2
5（t,J＝6.0Hz,1H）,2.58−2.78（m,1H）,2.86（d,J＝
7.3Hz,2H）,3.54（d,J＝6.5Hz,2H）,4.16（q,J＝5.0Hz,
1H）,5.12（m,1H）． 実施例 ４ 加熱還流したメタノール40ml、塩化アンモニウム2.5
g、亜鉛末8.2gからなる混合物中に、メタノール30mlに
溶解した（1S,5R,6R,7R）−4,4−ジクロル−６−アセト
キシメチル−７−アセトキシ−２−オキサビシクロ［3,
3,0］オクタン−３−オン13.5gを激しく撹拌しながら滴
下する。その後３時間撹拌後、加熱還流を行う。室温ま
で冷却後、濾過を行い、濾液を濃縮する。残留物を塩化
メチレン200mlに加熱溶解し、さらに濾過を行う。濾液
を濃縮して（1S,5R,6R,7R）−６−ヒドロキシメチル−
７−ヒドロキシ−２−オキサビシクロ［3,3,0］オクタ
ン−３−オン6.7gを得る。Melting point: 102-104 ° C. ▲ [α] 20 D ▼ = -45.0 ゜ (c = 1.0 methanol) 1 H NMR (90 MHz, D 2 O): δ = 2.06 (d, J = 4.5 Hz, 2H), 2.2
5 (t, J = 6.0Hz, 1H), 2.58-2.78 (m, 1H), 2.86 (d, J =
7.3Hz, 2H), 3.54 (d, J = 6.5Hz, 2H), 4.16 (q, J = 5.0Hz,
1H), 5.12 (m, 1H). Example 4 Heated refluxed methanol 40 ml, ammonium chloride 2.5
g, 8.2 g of zinc powder, dissolved in 30 ml of methanol, (1S, 5R, 6R, 7R) -4,4-dichloro-6-acetoxymethyl-7-acetoxy-2-oxabicyclo [3,
3,0] Octane-3-one (13.5 g) is added dropwise with vigorous stirring. After stirring for 3 hours, the mixture is heated and refluxed. After cooling to room temperature, filtration is performed, and the filtrate is concentrated. The residue is dissolved by heating in 200 ml of methylene chloride and filtered. The filtrate was concentrated to give (1S, 5R, 6R, 7R) -6-hydroxymethyl-
6.7 g of 7-hydroxy-2-oxabicyclo [3,3,0] octan-3-one are obtained.
物理特性は実施例３で得られた（1S,5R,6R,7R）−６
−ヒドロキシメチル−７−ヒドロキシ−２−オキサビシ
クロ［3,3,0］オクタン−３−オンと同様であった。Physical properties were obtained in Example 3 (1S, 5R, 6R, 7R) -6
-Hydroxymethyl-7-hydroxy-2-oxabicyclo [3,3,0] octan-3-one.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 Ｃｈｅｍｉｃａｌ Ａｂｓｔｒａｃｔ ｓ 100：156446 Ｃｈｅｍｉｃａｌ Ａｂｓｔｒａｃｔ ｓ 95：168615 (58)調査した分野(Int.Cl.6，ＤＢ名) C07D 307/935 ＣＡ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ)──────────────────────────────────────────────────続 き Continued on the front page (56) References Chemical Abstracts 100: 156446 Chemical Abstracts 95: 168615 (58) Fields investigated (Int. Cl. 6 , DB name) C07D 307/935 CA (STN) REGISTRY ( STN)
Claims (5)
す。） で表される光学活性ジクロルラクトン化合物。(1) General formula (Wherein, R is a hydrogen atom or represents an acetyl group.) An optically active dichlorlactone compound represented by the formula:
媒中にて、無水酢酸と強酸の存在下、ホルムアルデヒド
重合体と反応させることを特徴とする式 で表される光学活性ジクロルラクトンジアセテート化合
物の製造方法。(2) Reacting the optically active lactone compound represented by with a formaldehyde polymer in a halogenated carbon solvent in the presence of acetic anhydride and a strong acid. A method for producing an optically active dichlorolactone diacetate compound represented by the formula:
ルラクトンジアセテート化合物をメタノール溶媒中にて
塩化アンモニウム、亜鉛末を用いて脱クロル化反応と脱
アセチル化反応させることを特徴とする式 で表される光学活性ラクトンジオール化合物の製造方
法。3. A dechlorination reaction and a deacetylation reaction of the optically active dichlorolactone diacetate compound represented by the formula [Ia] using ammonium chloride and zinc dust in a methanol solvent. Expression A method for producing an optically active lactone diol compound represented by the formula:
ルラクトンジアセテート化合物を酸性の触媒存在下で加
水分解し、脱アセチル化反応させることを特徴とする式 で表される光学活性ジクロルラクトンジオール化合物の
製造方法。4. A formula comprising hydrolyzing an optically active dichlorolactone diacetate compound represented by the formula [Ia] in the presence of an acidic catalyst and subjecting the compound to a deacetylation reaction. A method for producing an optically active dichlorlactone diol compound represented by the formula:
ルラクトンジオール化合物を亜鉛末を用いて脱クロル化
反応させることを特徴とする前記式［III］で表される
光学活性ラクトンジオール化合物の製造方法。5. An optically active lactone represented by the formula [III], wherein the optically active dichlorolactone diol compound represented by the formula [Ib] is dechlorinated using zinc powder. A method for producing a diol compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14502190A JP2869745B2 (en) | 1990-06-01 | 1990-06-01 | Optically active dichlorlactone compound, method for producing the same, and method for producing optically active diol compound using the same |
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| Publication Number | Publication Date |
|---|---|
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| JP2869745B2 true JP2869745B2 (en) | 1999-03-10 |
Family
ID=15375599
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|---|---|
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1990
- 1990-06-01 JP JP14502190A patent/JP2869745B2/en not_active Expired - Lifetime
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| Title |
|---|
| Ｃｈｅｍｉｃａｌ Ａｂｓｔｒａｃｔｓ １００：１５６４４６ |
| Ｃｈｅｍｉｃａｌ Ａｂｓｔｒａｃｔｓ ９５：１６８６１５ |
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