JPH0551589B2 - - Google Patents
Info
- Publication number
- JPH0551589B2 JPH0551589B2 JP23485287A JP23485287A JPH0551589B2 JP H0551589 B2 JPH0551589 B2 JP H0551589B2 JP 23485287 A JP23485287 A JP 23485287A JP 23485287 A JP23485287 A JP 23485287A JP H0551589 B2 JPH0551589 B2 JP H0551589B2
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- compound
- dioxin
- terpene
- ones
- 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
- 150000001875 compounds Chemical class 0.000 claims description 13
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 8
- 150000004718 beta keto acids Chemical class 0.000 claims description 7
- 238000001308 synthesis method Methods 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims 3
- NFLGAXVYCFJBMK-BDAKNGLRSA-N (-)-menthone Chemical compound CC(C)[C@@H]1CC[C@@H](C)CC1=O NFLGAXVYCFJBMK-BDAKNGLRSA-N 0.000 description 12
- -1 acetyl Meldrum's acid Chemical compound 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- URHWMZVMAAUENN-UHFFFAOYSA-N 1,3-dioxin-4-one Chemical class O=C1OCOC=C1 URHWMZVMAAUENN-UHFFFAOYSA-N 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- UFVDXRZDNSEHDT-UHFFFAOYSA-N undec-2-ene Chemical compound [CH2]CCCCCCCC=CC UFVDXRZDNSEHDT-UHFFFAOYSA-N 0.000 description 3
- WHBMMWSBFZVSSR-GSVOUGTGSA-N (R)-3-hydroxybutyric acid Chemical compound C[C@@H](O)CC(O)=O WHBMMWSBFZVSSR-GSVOUGTGSA-N 0.000 description 2
- WHBMMWSBFZVSSR-VKHMYHEASA-N (S)-3-hydroxybutyric acid Chemical compound C[C@H](O)CC(O)=O WHBMMWSBFZVSSR-VKHMYHEASA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- DELRMBDZSMPFPS-UHFFFAOYSA-N 5-(hydroxymethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione Chemical compound CC1(C)OC(=O)C(=CO)C(=O)O1 DELRMBDZSMPFPS-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NFLGAXVYCFJBMK-RKDXNWHRSA-N (+)-isomenthone Natural products CC(C)[C@H]1CC[C@@H](C)CC1=O NFLGAXVYCFJBMK-RKDXNWHRSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- NWHKKDLPTKZXQK-UHFFFAOYSA-N 1,2-dioxin-4-one Chemical compound O=C1COOC=C1 NWHKKDLPTKZXQK-UHFFFAOYSA-N 0.000 description 1
- 150000000190 1,4-diols Chemical class 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- UCZQXJKDCHCTAI-UHFFFAOYSA-N 4h-1,3-dioxine Chemical compound C1OCC=CO1 UCZQXJKDCHCTAI-UHFFFAOYSA-N 0.000 description 1
- PYJQNMUDOQASPX-UHFFFAOYSA-N 5-methyl-5-phenyl-2-propan-2-ylcyclohexan-1-ol Chemical compound C1C(O)C(C(C)C)CCC1(C)C1=CC=CC=C1 PYJQNMUDOQASPX-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- NFLGAXVYCFJBMK-UHFFFAOYSA-N Menthone Chemical compound CC(C)C1CCC(C)CC1=O NFLGAXVYCFJBMK-UHFFFAOYSA-N 0.000 description 1
- LQCYIQBYFCQMCH-UHFFFAOYSA-N [Li].C[Cu]C Chemical compound [Li].C[Cu]C LQCYIQBYFCQMCH-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229930007503 menthone Natural products 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Landscapes
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、エナンチオ選択的合成法に関し、特
にキラルな１，３−ジオキシン−４−オン類から
光学活性なカルボニル化合物のエナンチオ選択的
合成法に関する。Detailed Description of the Invention (Industrial Application Field) The present invention relates to an enantioselective synthesis method, and in particular to an enantioselective synthesis method of optically active carbonyl compounds from chiral 1,3-dioxin-4-ones. Regarding.
（従来の技術）
１，３−ジオキシン−４−オン類のうち、２，
２−ジ置換体である２，２−ジメチル−１，３−
ジオキシン−４−オンについて、本発明者らは先
にこれらを高収率で製造する方法を提案した（特
開昭61−17580）。(Prior art) Among 1,3-dioxin-4-ones, 2,
2-disubstituted 2,2-dimethyl-1,3-
Regarding dioxin-4-one, the present inventors have previously proposed a method for producing them in high yield (Japanese Patent Application Laid-Open No. 17580/1983).
この２，２−ジ置換体は、いずれも生理活性化
合物あるいは機能性物質を合成する中間体として
有用であるが、得られる化合物はそのままでは、
dl−体であつて、されに高度の機能を必要とする
場合は、例えば光学分割などの手段を必要とし
た。 All of these 2,2-disubstituted products are useful as intermediates for synthesizing physiologically active compounds or functional substances, but the resulting compounds are
If the dl-form requires advanced functionality, a method such as optical resolution is required.
（発明が解決しようとする問題点）
反応生成物を直接光学活性体として得るために
は、前述のようにdl−体を何らかの手段によつて
他の光学活性体と造塩、結晶化させた後、分別晶
析、次いで分解する方法が公知であり、実用化さ
れている例も多いが、その操作は極めて複雑であ
る。また、別に出発材料を天然系の光学活性体か
ら選び、これから誘導する方法もあるが、反応途
中でラセミ化、または反転などが起きるため、利
用し得る反応は極めて限られる。(Problems to be Solved by the Invention) In order to directly obtain the reaction product as an optically active form, the dl- form must be salted and crystallized with another optically active form by some means as described above. A method of subsequent fractional crystallization and then decomposition is known and has been put into practical use in many cases, but the operation is extremely complicated. Alternatively, there is a method of selecting a starting material from a naturally occurring optically active substance and deriving it from this, but since racemization or inversion occurs during the reaction, the usable reactions are extremely limited.
これに対し、本発明者らは先に見出した方法の
応用により、基本骨格の１，３−ジオキシン−４
−オン自体に光学活性な基を付与し、以後の合成
反応において、その基に立体抑制を行わせること
により、反応生成物を光学活性体として直接取得
することを目的として、１，３−ジオキシン−４
−オンの２位に立体制御可能な空間的広がりを有
する光学活性基を誘導し、キラルな１，３−ジオ
キシン−４−オン類の合成法を検討した。 In contrast, by applying the method discovered earlier, the present inventors found that the basic skeleton of 1,3-dioxin-4
1,3-dioxin with the aim of directly obtaining the reaction product as an optically active form by adding an optically active group to -one itself and sterically suppressing that group in the subsequent synthesis reaction. -4
We investigated a method for synthesizing chiral 1,3-dioxin-4-ones by inducing an optically active group with stereocontrollable spatial extension at the 2-one position.
さらにこのキラルな１，３−ジオキシン−４−
オン類から光学活性なカルボニル化合物をエナン
チオ選択的に合成する方法を検討し、本発明を完
成した。 Furthermore, this chiral 1,3-dioxin-4-
The present invention was completed by studying a method for enantioselectively synthesizing optically active carbonyl compounds from ons.
（問題点を解決するための手段）
本発明は、キラルな１，３−ジオキシン−４−
オン類を、アルキル化、還元および光照射の群か
ら選ばれる方法により反応させ、光学活性なカル
ボニル化合物をエナンチオ選択的に得ることを特
徴とするエナンチオ選択的合成法である。(Means for solving the problems) The present invention provides chiral 1,3-dioxin-4-
This is an enantioselective synthesis method characterized by reacting ons by a method selected from the group of alkylation, reduction, and photoirradiation to enantioselectively obtain an optically active carbonyl compound.
キラルな１，３−ジオキシン−４−オン類は、
β−ケト酸、その誘導体またはそれらの等価体と
光学活性なテルペン様化合物とを結合させること
により得られる。この１，３−ジオキシン−４−
オン類は次式：
（式中のＸはテルペン様化合物由来の光学活性
基を示し、ＹおよびＺは水素原子および低級アル
キルから選ばれる置換基を示す）で表される光学
活性な環状構造を有する。 Chiral 1,3-dioxin-4-ones are
It can be obtained by combining a β-keto acid, a derivative thereof, or an equivalent thereof with an optically active terpene-like compound. This 1,3-dioxin-4-
The on class is the following formula: It has an optically active cyclic structure represented by (in the formula, X represents an optically active group derived from a terpene-like compound, and Y and Z represent substituents selected from a hydrogen atom and lower alkyl).
β−ケト酸、その誘導体またはそれらの等価体
は、α位およびβ位が水素原子および低級アルキ
ル基で置換されている鎖状または環状のものであ
ればその種類を問わず、いずれも原料とすること
ができ、その内でも特に、β−ケト酸tert−ブチ
ルエステル、２，２，−ジメチル−１，３−ジオ
キシン−４−オンの様な２，２−ジアルキル−
１，３−ジオキシン−４−オン、ホルミルメルド
ラム酸、アセチルメルドラム酸等が好ましい。 β-keto acids, their derivatives, or their equivalents can be used as raw materials regardless of their type as long as they are chain or cyclic in which the α and β positions are substituted with hydrogen atoms and lower alkyl groups. Among them, 2,2-dialkyl- such as β-keto acid tert-butyl ester, 2,2,-dimethyl-1,3-dioxin-4-one, etc.
Preferred are 1,3-dioxin-4-one, formyl Meldrum's acid, acetyl Meldrum's acid, and the like.
光学活性なテルペン様化合物としては、ｌ−メ
ントン、ｄ−カンフアー、（＋）または（−）−８
−フエニルメントール等の炭素数10個を基本骨格
に有するテルペン様化合物またはその誘導体を用
いることができる。特に収率の点からｌ−メント
ンが好ましい。 Optically active terpene-like compounds include l-menthone, d-camphor, (+) or (-)-8
- A terpene-like compound having a basic skeleton of 10 carbon atoms, such as phenylmenthol, or a derivative thereof can be used. In particular, l-menthone is preferred from the viewpoint of yield.
β−ケト酸、その誘導体またはそれらの等価体
と光学活性なテルペン様化合物を結合させて得ら
れたキラルな１，３−ジオキシン−４−オン類
は、次にアルキル化、好ましくはメチル化、還元
および光照射の群から選ばれる方法により反応さ
せ、光学活性なカルボニル化合物をエナンチオ選
択的に得る。 Chiral 1,3-dioxin-4-ones obtained by combining β-keto acids, their derivatives, or their equivalents with optically active terpene-like compounds are then alkylated, preferably methylated. The reaction is performed by a method selected from the group of reduction and photoirradiation to enantioselectively obtain an optically active carbonyl compound.
（発明の効果）
本発明によれば、従来のβ−ケト酸とカルボニ
ル化合物との反応により１，３−ジオキシン−４
−オンの２，２−ジ置換体を製造する方法を、さ
らに発展させて、２位に光学活性な基を導入し、
１，３−ジオキシン−４−オンの２位に立体制御
可能な空間的広がりを有する光学活性基を誘導
し、キラルな１，３−ジオキシン−４−オン類を
合成することができると共に、光学活性なカルボ
ニル化合物をエナンチオ選択的に得ることができ
る。(Effects of the Invention) According to the present invention, 1,3-dioxin-4
The method for producing 2,2-disubstituted -one was further developed by introducing an optically active group at the 2-position,
Chiral 1,3-dioxin-4-ones can be synthesized by inducing an optically active group with a stereoscopically controllable spatial extent at the 2-position of 1,3-dioxin-4-one, and optically Active carbonyl compounds can be obtained enantioselectively.
（実施例）
以下、参考例および実施例により本発明を詳細
に説明する。(Examples) Hereinafter, the present invention will be explained in detail using reference examples and examples.
参考例 １
（6S，7R，10R）−および（6R，7R，10R）−
10−メチル−７−イソプロピル−４−オキソ−
１，５−ジオキサスピロ〔5.5〕ウンデセ−２−
エン（(1)および(2)）
ａ 0.86ｇ（5mmol）のホルミルメルドラム酸
を、3.85ｇ（25mmol）のｌ−メントンを含む
20mlの沸騰トルエン中に約５分間かけて徐々に
加え、更に10分加熱還流した。反応液をシリカ
ゲルカラムクロマトグラフイに付し、ヘキサン
−酢酸エチル（50：１）で展開して、先ずｌ−
メントンの過剰を回収した。次いで、ヘキサン
−酢酸エチル10：１で展開し、(1)と(2)のほぼ等
量の混合物を0.56ｇ（25％）得た。この混合物
を約200倍のシリカゲルカラムクロマトグラフ
イー（ヘキサン−エーテル、30：１）で分離
し、(1)と(2)を得た。Reference example 1 (6S, 7R, 10R) - and (6R, 7R, 10R) -
10-methyl-7-isopropyl-4-oxo-
1,5-dioxaspiro[5.5]undec-2-
Ene ((1) and (2)) a Contains 0.86 g (5 mmol) of formyl Meldrum's acid and 3.85 g (25 mmol) of l-menthone
The mixture was gradually added to 20 ml of boiling toluene over about 5 minutes, and heated under reflux for an additional 10 minutes. The reaction solution was subjected to silica gel column chromatography and developed with hexane-ethyl acetate (50:1).
An excess of menthone was recovered. Next, the mixture was developed with hexane-ethyl acetate 10:1 to obtain 0.56 g (25%) of a mixture of (1) and (2) in approximately equal amounts. This mixture was separated by about 200 times silica gel column chromatography (hexane-ether, 30:1) to obtain (1) and (2).
ｂ 1.28ｇ（10mmol）の２，２−ジメチル−１，
３−ジオキシン−４−オンと7.9ｇ（50mmol）
のｌ−メントンのベンゼン溶液を２時間加熱還
流した。ａ）と同様に後処理、精製し、(1)と(2)
を得た。b 1.28 g (10 mmol) of 2,2-dimethyl-1,
7.9g (50mmol) of 3-dioxin-4-one
A solution of l-menthone in benzene was heated under reflux for 2 hours. After treatment and purification in the same manner as in a), (1) and (2)
I got it.
(1)の収率 29％、(2)の収率 30％。Yield of (1): 29%, yield of (2): 30%.
(1) 融点115〜116℃（ペンタンより再結晶、プリ
ズム晶）
〔α〕24 D−51.6°（CHCl3）
IR（CHCl3）：1730，1620cm-1
1H−NMR（CDCl3）δ：5.25，7.08
（各1H、ｄ，Ｊ＝6Hz）、（C2Ｈ及びC3Ｈ）
分析値 C15H24O3
計算値 Ｃ 71.39， Ｈ 9.59
実験値 Ｃ 71.45， Ｈ 9.50
(2) 融点100〜101℃（ペンタンより再結晶、プリ
ズム晶）
〔α〕25 D−17.7°（CHCl3）
IR（CHCl3）：1730，1620cm-1
1H−NMR（CDCl3）δ：5.32，7.08
（各1H、ｄ，Ｊ＝6Hz）、（C2Ｈ及びC3Ｈ）
分析値 C15H24O3
計算値 Ｃ 71.39， Ｈ 9.59
実験値 Ｃ 71.30， Ｈ 9.48
参考例 ２
（6S，7R，10R）−および（6R，7R，10R）−
２，10−ジメチル−７−イソプロピル−４−オキ
ソ−１，５−ジオキサスピロ〔5.5〕ウンデセ−
２−エン（(3)および(4)）
ａ 1.86ｇ（10mmol）のアセチルメルドラム酸
と7.7ｇ（50mmol）のｌ−メントンのトルエン
（30ml）溶液を30分間加熱還流した。シリカゲ
ルカラムクロマトグラフイ（ヘキサン−酢酸エ
チル50：１→20：１）で精製し、(3)と(4)の混合
物（約１：１）1.64ｇを油状物として得た（収
率69％）。また、同反応をベンゼン中、加熱下
で約10時間行うと66％の収率であつた。(3)と(4)
の混合物は、中圧カラムクロマトグラフイ−で
分離され、ペンタンより再結晶して結晶を得
た。(1) Melting point 115-116℃ (recrystallized from pentane, prismatic crystal) [α] 24 D −51.6° (CHCl 3 ) IR (CHCl 3 ): 1730, 1620 cm −1 1 H−NMR (CDCl 3 ) δ: 5.25, 7.08 (1H, d, J = 6Hz each), (C 2 H and C 3 H) Analytical value C 15 H 24 O 3 Calculated value C 71.39, H 9.59 Experimental value C 71.45, H 9.50 (2) Melting point 100 ~101℃ (recrystallized from pentane, prismatic crystal) [α] 25 D −17.7° (CHCl 3 ) IR (CHCl 3 ): 1730, 1620 cm -1 1 H−NMR (CDCl 3 ) δ: 5.32, 7.08 (each 1H, d, J=6Hz), (C 2 H and C 3 H) Analytical value C 15 H 24 O 3 Calculated value C 71.39, H 9.59 Experimental value C 71.30, H 9.48 Reference example 2 (6S, 7R, 10R) − and (6R, 7R, 10R) −
2,10-dimethyl-7-isopropyl-4-oxo-1,5-dioxaspiro[5.5]undec-
2-ene ((3) and (4)) a A solution of 1.86 g (10 mmol) acetylmeldrum's acid and 7.7 g (50 mmol) l-menthone in toluene (30 ml) was heated under reflux for 30 minutes. Purification by silica gel column chromatography (hexane-ethyl acetate 50:1 → 20:1) gave 1.64 g of a mixture of (3) and (4) (approximately 1:1) as an oil (yield 69%). ). When the same reaction was carried out in benzene under heating for about 10 hours, the yield was 66%. (3) and (4)
The mixture was separated by medium pressure column chromatography and recrystallized from pentane to obtain crystals.
ｂ 1.68ｇ（20mmol）のジケテン、3.08ｇ
（20mmol）のｌ−メントンおよび50mgのｐ−
トルエンスルホン酸の混合物を２時間加熱還流
する。ａ）と同様に精製し、(3)と(4)の混合物
（約２：１）2.1ｇを油状物として得た（収率44
％）。また、この反応を200mgのｐ−トルエンス
ルホン酸を用いて室温下で４日間放置の条件で
約10時間行うと(3)と(4)の混合物（約５：１）を
45％の収率で得た。b 1.68 g (20 mmol) diketene, 3.08 g
(20 mmol) l-menthone and 50 mg p-
The toluenesulfonic acid mixture is heated to reflux for 2 hours. Purification was carried out in the same manner as in a) to obtain 2.1 g of a mixture of (3) and (4) (approximately 2:1) as an oil (yield: 44
%). Furthermore, when this reaction is carried out using 200 mg of p-toluenesulfonic acid and left for 4 days at room temperature for about 10 hours, a mixture of (3) and (4) (about 5:1) is obtained.
Obtained with a yield of 45%.
(3) 融点26〜27℃（プリズム晶）
〔α〕27 D−30.3°（CHCl3）
分析値 C14H22O3
計算値 Ｃ 68.99， Ｈ 9.80
実験値 Ｃ 68.78， Ｈ 9.71
(4) 融点56.5〜58℃（針状）
〔α〕27 D−31.5°（CHCl3）
分析値 C14H22O3
計算値 Ｃ 68.99， Ｈ 9.80
実験値 Ｃ 69.10， Ｈ 9.85
実施例 １
３−ヒドロキシ酪酸の合成
ａ（6S，7R，10R）−10−メチル−７−イソプロ
ピル−４−オキソ−１，５−ジオキサスピロ
〔5.5〕ウンデセ−２−エン(1)のメチル化による
（Ｒ）−３−ヒドロキシ酪酸の合成
無水エーテル中で常法に従い、ジメチル銅リチ
ウム（1mmol）を調製した。−78℃に冷却し、
224mg（1mmol）の(1)の無水エーテル溶液を加
え、同温度で3.5時間かきまぜた。塩化アンモニ
ウム80mgと28％水酸化アンモニウムの混合物を加
え、室温に保つ。エーテルで抽出し、エーテル層
に0.1N塩酸を0.3ml加え、室温で３時間かきまぜ
た。減圧下で濃縮し、残渣をシリカゲルカラムク
ロマトグラフイで精製し、油状の（Ｒ）−３−ヒ
ドロキシ酪酸を60mg得た。収率59％。(3) Melting point 26-27℃ (prismatic crystal) [α] 27 D −30.3° (CHCl 3 ) Analytical value C 14 H 22 O 3 Calculated value C 68.99, H 9.80 Experimental value C 68.78, H 9.71 (4) Melting point 56.5-58℃ (acicular) [α] 27 D -31.5° (CHCl 3 ) Analytical value C 14 H 22 O 3 Calculated value C 68.99, H 9.80 Experimental value C 69.10, H 9.85 Example 1 of 3-hydroxybutyric acid Synthesis a (R)-3-hydroxybutyric acid by methylation of (6S,7R,10R)-10-methyl-7-isopropyl-4-oxo-1,5-dioxaspiro[5.5]undec-2-ene (1) Synthesis Dimethyl copper lithium (1 mmol) was prepared in anhydrous ether according to a conventional method. Cool to −78℃,
A solution of 224 mg (1 mmol) of (1) in anhydrous ether was added, and the mixture was stirred at the same temperature for 3.5 hours. Add a mixture of 80 mg ammonium chloride and 28% ammonium hydroxide and keep at room temperature. After extraction with ether, 0.3 ml of 0.1N hydrochloric acid was added to the ether layer, and the mixture was stirred at room temperature for 3 hours. It was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 60 mg of oily (R)-3-hydroxybutyric acid. Yield 59%.
〔α〕28 D−20.1°（H2Ｏ） 光学純度 82％。 [α] 28 D −20.1° (H 2 O) Optical purity 82%.
ｂ（6S，7R，10R）−２，10−ジメチル−７−イ
ソプロピル−４−オキソ−１，５−ジオキサス
ピロ〔5.5〕ウンデセ−２−エン(3)の還元によ
る（ｓ）−３−ヒドロキシ酪酸の合成
119mg（0.5mmol）の(3)を10％pd−Ｃ（100mg）
を用いてメタノール中、常圧で接触還元する。メ
タノールを留去し、シリカゲルカラムクロマトグ
ラフイで精製し、（Ｓ）−３−ヒドロキシ酪酸を油
状物として得た。(s)-3-hydroxybutyric acid by reduction of b(6S,7R,10R)-2,10-dimethyl-7-isopropyl-4-oxo-1,5-dioxaspiro[5.5]undec-2-ene (3) Synthesis of 119 mg (0.5 mmol) of (3) with 10% PD-C (100 mg)
catalytic reduction in methanol at normal pressure using Methanol was distilled off and the residue was purified by silica gel column chromatography to obtain (S)-3-hydroxybutyric acid as an oil.
収率 38％、光学純度 88％。 Yield 38%, optical purity 88%.
〔α〕28 D＋21.5°（H2Ｏ）
実施例 ２
アルデヒドラクトンの合成
228mg（1mmol）の（6S，7R，10R）−10−メ
チル−７−イソプロピル−４−オキソ−１，５−
ジオキサスピロ〔5.5〕ウンデセ−２−エン(1)と
1.0mg（10mmol）のシス−２−シクロペンテン−
１，４−ジオールの酢酸エチル（100ml）溶液を
高圧水銀燈（パイレツクスまたはパイコールフイ
ルター付）で照射する。(1)の消失後、反応液を水
で抽出し、水溶性のジオールを回収する。有機層
を濃縮し、水10mlと２時間加熱還流する。ジクロ
ロメタンで抽出し、粗製のアルデヒドラクトンを
得る。水層を再び２時間加熱後、ジクロロメタン
で抽出する。ジクロロメタン抽出分を合わせて薄
層クロマトグラフイーで精製し、（＋）−アルデヒ
ドラクトンを46mg得た。収率30％。 [α] 28 D +21.5° (H 2 O) Example 2 Synthesis of aldehyde lactone 228 mg (1 mmol) of (6S,7R,10R)-10-methyl-7-isopropyl-4-oxo-1,5-
Dioxaspiro [5.5] undec-2-ene (1) and
1.0 mg (10 mmol) of cis-2-cyclopentene
A solution of 1,4-diol in ethyl acetate (100 ml) is irradiated with a high-pressure mercury lamp (equipped with a Pyrex or Pycoll filter). After the disappearance of (1), the reaction solution is extracted with water to recover the water-soluble diol. The organic layer is concentrated and heated under reflux with 10 ml of water for 2 hours. Extract with dichloromethane to obtain the crude aldehyde lactone. The aqueous layer is heated again for 2 hours and then extracted with dichloromethane. The dichloromethane extracts were combined and purified by thin layer chromatography to obtain 46 mg of (+)-aldehyde lactone. Yield 30%.
〔α〕24 D＋170°（CHCl3）光学純度 72％。 [α] 24 D +170° (CHCl 3 ) Optical purity 72%.
Claims (1)
体と光学活性なテルペン様化合物とを結合させた
次式： （式中のＸはテルペン様化合物由来の光学活性
基を示し、ＹおよびＺは水素原子、低級アルキル
基およびアシル基から選ばれる置換基を示す）で
表される光学活性な環状構造であるキラルな１，
３−ジオキシン−４−オン類を、アルキル化反応
させ、光学活性なカルボニル化合物をエナンチオ
選択的に得ることを特徴とするエナンチオ選択的
合成法。 ２ β−ケト酸、その誘導体またはそれらの等価
体と光学活性なテルペン様化合物を結合させた次
式： （式中のＸはテルペン様化合物由来の光学活性
基を示し、ＹおよびＺは水素原子、低級アルキル
基およびアシル基から選ばれる置換基を示す）で
表される光学活性な環状構造であるキラルな１，
３−ジオキシン−４−オン類を、還元により反応
させ、光学活性なカルボニル化合物をエナンチオ
選択的に得ることを特徴とするエナンチオ選択的
合成法。 ３ β−ケト酸、その誘導体またはそれらの等価
体と光学活性なテルペン様化合物を結合させた次
式： （式中のＸはテルペン様化合物由来の光学活性
基を示し、ＹおよびＺは水素原子、低級アルキル
基およびアシル基から選ばれる置換基を示す）で
表される光学活性な環状構造であるキラルな１，
３−ジオキシン−４−オン類を、光照射により反
応させ、光学活性なカルボニル化合物をエナンチ
オ選択的に得ることを特徴とするエナンチオ選択
的合成法。[Claims] 1. The following formula in which a β-keto acid, its derivative, or its equivalent is combined with an optically active terpene-like compound: (In the formula, X represents an optically active group derived from a terpene-like compound, and Y and Z represent substituents selected from a hydrogen atom, a lower alkyl group, and an acyl group.) Na1,
An enantioselective synthesis method characterized by subjecting 3-dioxin-4-ones to an alkylation reaction to enantioselectively obtain an optically active carbonyl compound. 2 The following formula in which a β-keto acid, its derivative or its equivalent is combined with an optically active terpene-like compound: (In the formula, X represents an optically active group derived from a terpene-like compound, and Y and Z represent substituents selected from a hydrogen atom, a lower alkyl group, and an acyl group.) Na1,
An enantioselective synthesis method characterized by reacting 3-dioxin-4-ones by reduction to enantioselectively obtain an optically active carbonyl compound. 3 The following formula in which a β-keto acid, its derivative or its equivalent is combined with an optically active terpene-like compound: (In the formula, X represents an optically active group derived from a terpene-like compound, and Y and Z represent substituents selected from a hydrogen atom, a lower alkyl group, and an acyl group.) Na1,
An enantioselective synthesis method characterized by reacting 3-dioxin-4-ones by light irradiation to enantioselectively obtain an optically active carbonyl compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23485287A JPS6479174A (en) | 1987-09-21 | 1987-09-21 | Selective synthesis of enantiomer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23485287A JPS6479174A (en) | 1987-09-21 | 1987-09-21 | Selective synthesis of enantiomer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6479174A JPS6479174A (en) | 1989-03-24 |
| JPH0551589B2 true JPH0551589B2 (en) | 1993-08-03 |
Family
ID=16977363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP23485287A Granted JPS6479174A (en) | 1987-09-21 | 1987-09-21 | Selective synthesis of enantiomer |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6479174A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5108087B2 (en) | 2008-02-27 | 2012-12-26 | グローリー株式会社 | Paper sheet processing equipment |
-
1987
- 1987-09-21 JP JP23485287A patent/JPS6479174A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6479174A (en) | 1989-03-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2099444C (en) | Process for preparing tert-butyl (3r,5s)-6-hydroxy-3,5-o- isopropylidene-3,5-dihydroxyhexanoate | |
| Shing et al. | Catalytic asymmetric epoxidation of alkenes with arabinose-derived uloses | |
| JP3351563B2 (en) | Method for producing 3-hydroxybutyric acid derivative | |
| Singh et al. | Synthesis of enantiomerically pure all cis-2, 3, 6-trisubstituted piperidine: a silicon mediated total synthesis of (+)-carpamic acid | |
| Toya et al. | Stereocontrolled total synthesis and biological evaluation of (−)-and (+)-petrosin and its derivatives | |
| JPH0551589B2 (en) | ||
| Kishida et al. | Diacetone-glucose architecture as a chirality template. Part 9. 1 Enantioselective synthesis of (R)-mevalonolactone and (R)-[2 H 9] mevalonolactone on carbohydrate template | |
| Liu et al. | Coumarins via the wittig reaction. Synthesis of methoxsalen‐5‐14C | |
| US4454352A (en) | Pure enantiomers of bicyclo[2.2.2]oct-5-en-2-ones, processes for their production and their use | |
| EP0583171A2 (en) | (3R,5S)-3,5,6-trihydroxyhexanoic acid derivatives and methods for their production | |
| WO2002022618A1 (en) | Method for preparing camptothecin and its derivatives | |
| Sato et al. | Use of 1, 3‐dioxin‐4‐ones and their related compounds in synthesis. Part 28. Asymmetric de mayo reactions using chiral spirocyclic dioxinones | |
| Żurawiński et al. | Stereocontrolled synthesis of enantiopure anticancer cyclopentenone prostaglandin analogues:(−)-and (+)-TEI-9826 | |
| CN1107848A (en) | Preparation of imidazopyridir derivative | |
| GB2036744A (en) | Eburnane derivatives | |
| JP2557087B2 (en) | Asymmetric photochemical reaction method | |
| EP0585104A1 (en) | A method of preparing a saturated monocyclic hydrocarbon compound and an intermediate therefor | |
| EP0217375B1 (en) | Process for preparing optically active carbonyl compounds | |
| JP3986606B2 (en) | Synthetic intermediates useful for the synthesis of the A ring moiety of vitamin D derivatives, methods for their preparation and methods for their use | |
| JP4122389B2 (en) | Process for producing optically active dihydrocaranone | |
| EP0194840B1 (en) | Process for producing an aldehydelactone | |
| Banachowicz et al. | General strategy for the synthesis of unsaturated carbasugars via a diastereoselective seleno-Michael/aldol reaction | |
| Wróblewski et al. | Synthesis of diethyl (1R, 2R)-and (1S, 2R)-3-acetamido-1, 2-dihydroxypropylphosphonates | |
| JP3882856B2 (en) | Method for producing α-fluoro-β-ketoester | |
| de la Rosa et al. | Palladium-catalyzed allylic nucleophilic substitution reactions of (E)-γ-acetoxy-α, β-unsaturated p-tolylsulfoxides |