JPH03181433A - Direct resolution for 1-p-substituted phenylethanol - Google Patents
Direct resolution for 1-p-substituted phenylethanolInfo
- Publication number
- JPH03181433A JPH03181433A JP32095589A JP32095589A JPH03181433A JP H03181433 A JPH03181433 A JP H03181433A JP 32095589 A JP32095589 A JP 32095589A JP 32095589 A JP32095589 A JP 32095589A JP H03181433 A JPH03181433 A JP H03181433A
- Authority
- JP
- Japan
- Prior art keywords
- optical resolution
- polysaccharide
- para
- separating agent
- cellulose
- 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.)
- Pending
Links
- -1 1-p-substituted phenylethanol Chemical class 0.000 title claims description 12
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 21
- 239000005017 polysaccharide Substances 0.000 claims abstract description 21
- 230000003287 optical effect Effects 0.000 claims abstract description 18
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
- 238000004811 liquid chromatography Methods 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 3
- 150000004676 glycans Chemical class 0.000 claims abstract 3
- 238000000034 method Methods 0.000 claims description 19
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical class OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- VLVILBSSXMZZCB-UHFFFAOYSA-N 1-[4-(2-methylpropyl)phenyl]ethanol Chemical compound CC(C)CC1=CC=C(C(C)O)C=C1 VLVILBSSXMZZCB-UHFFFAOYSA-N 0.000 claims 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 238000006243 chemical reaction Methods 0.000 abstract description 2
- 238000004587 chromatography analysis Methods 0.000 abstract description 2
- 239000004973 liquid crystal related substance Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 abstract 1
- 238000012986 modification Methods 0.000 abstract 1
- 230000004048 modification Effects 0.000 abstract 1
- 150000004804 polysaccharides Chemical class 0.000 description 18
- 239000002904 solvent Substances 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 238000000053 physical method Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000004381 surface treatment Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- SBTVLCPCSXMWIQ-UHFFFAOYSA-N (3,5-dimethylphenyl) carbamate Chemical compound CC1=CC(C)=CC(OC(N)=O)=C1 SBTVLCPCSXMWIQ-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 229920002498 Beta-glucan Polymers 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- 229920001202 Inulin Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-RWOPYEJCSA-N beta-D-mannose Chemical compound OC[C@H]1O[C@@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-RWOPYEJCSA-N 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000010701 ester synthesis reaction Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 1
- 229940029339 inulin Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 238000002444 silanisation Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229920001221 xylan Polymers 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は１−ノ４う置換フェニルエタノールの直接光学
分割方法に関するものである。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a method for direct optical resolution of 1-4-substituted phenylethanol.
（従来の技術及び問題点）
光学活性１−ノヤジ置換フェニルエタノールは、医薬中
間体や液晶化合物の中間体として有用な化合物である。(Prior Art and Problems) Optically active 1-noyadi-substituted phenylethanol is a compound useful as a pharmaceutical intermediate or an intermediate for liquid crystal compounds.
これまで１−ノ々う置換フェニルエタノールの光学分割
法としては、イソグロピルカルＩ４メート体に誘導し光
学活性な分離剤を使ったガスクロマトグ２フィーによう
分析する方法（５ｃｈｎｓｌｄＩｒらＪ、Ｃｈｅｍ、８
ｏｃ、、Ｃｈ＠ｍ、Ｃｏｍｍｕｎｓ （２２）ｓ１４５
９ （Ｉ９８Ｂ） ）−また、哺乳類ｔたは鳥類の肝臓
破砕物を用いて１−ノ臂う置換フェニルエタノールの脂
肪酸エステルを不斉加水分解する方法（ｑ＃開昭６０−
２２４４９４ ）、エステラーゼ活性を有する酵素によ
る不斉エステル合成反応を利用する方法（特開昭６３−
１１９６９３、特開平１−２１５２９８）が知られてい
るが、光学活性な１−ノ々う置換フェニルエタノールの
生成工程の後、単離・精製工程が必要であシ、操作が繁
雑である。これまで１−パラ置換フェニルエタノールを
誘導体にすることなしに直接光学分割する方法は知られ
てからす、したがって、ｌ−パラ置換フェニルエタノー
ルのエナンチオマーの混合物をその１１直接光学分割す
る方法を供することは、極めて有益なことである。Up until now, the optical resolution method for 1-nono-substituted phenylethanol has been to induce the isoglopylic I4mate form and analyze it using gas chromatography using an optically active separating agent (5chnsldIr et al. J, Chem, 8
oc,, Ch@m, Communs (22) s145
9 (I98B)) - In addition, a method for asymmetrically hydrolyzing fatty acid esters of 1-substituted phenylethanol using crushed mammalian or bird liver (q# Kaisho 60-
224494), a method using an asymmetric ester synthesis reaction using an enzyme having esterase activity (Japanese Unexamined Patent Application Publication No. 1983-1999)
No. 119693, JP-A-1-215298) is known, but it requires an isolation and purification step after the step of producing optically active 1-non-substituted phenylethanol, and the operation is complicated. Until now, no method has been known for directly optically resolving 1-para-substituted phenylethanol without derivatizing it. Therefore, the present invention provides a method for directly optically resolving a mixture of enantiomers of 1-para-substituted phenylethanol. is extremely beneficial.
（Ｌ１題を解決するための手段）
本発明者らは、鋭意検討した結果、ｌ−ノ＃う置換フェ
ニルエタノールを多糖誘導体を光学活性な固定相とする
液体クロマドグ２フイーの光学分割によシ、光学分割し
得ることを見出だして本発明に到達した。即ち、本発明
は、−数式
（式中、Ｒは炭素数３〜２０のアルキル基もしくはアル
コキシ基を示す。傘は不斉炭素原子を示す。）で示され
る】−ノ９ツ置換フェニルエタノールのエナンチオマー
の混合物をそのオま直接、多糖又はその誘導体を有効成
分とする分離剤によって液体クロマトグラフィー−によ
う光学分割する方法に関するものである。(Means for Solving Problem L1) As a result of intensive studies, the present inventors have determined that l-substituted phenylethanol can be synthesized by optical resolution using a liquid chroma dog 2 feed using a polysaccharide derivative as an optically active stationary phase. The present invention was achieved by discovering that optical resolution can be performed. That is, the present invention provides -9-substituted phenylethanol represented by the formula (wherein R represents an alkyl group or an alkoxy group having 3 to 20 carbon atoms; the umbrella represents an asymmetric carbon atom). The present invention relates to a method for optically resolving a mixture of enantiomers directly using liquid chromatography using a separation agent containing a polysaccharide or a derivative thereof as an active ingredient.
本発明は、１−パラ置換フェニルエタノールの光学純度
分析にも応用可能である。特に、パラ位の置換基が炭素
数３〜２０のアルキル基もしくはアルコキシ基の１−パ
ラ置換フェニルエタノールについては、光学純度の分析
法は、比旋光度の測定以外知られていないが、本発明を
適用すれば簡便かつ迅速に光学純度を決定することがで
きる。The present invention is also applicable to optical purity analysis of 1-para-substituted phenylethanol. In particular, for 1-para-substituted phenylethanol in which the substituent at the para position is an alkyl group or an alkoxy group having 3 to 20 carbon atoms, there is no known analytical method for optical purity other than measurement of specific optical rotation. By applying this method, optical purity can be determined easily and quickly.
次に本発明について詳細に述べる。Next, the present invention will be described in detail.
上記−数式（Ｉ）にかいてＲで示されるアルキル基もし
くはアルコキシ基の具体例として、グロビル基、ブチル
基、ペンチル基、ヘキシル基、オクチル基、デシル基、
ペンチルオキシ基、プロポキシ基、ブトキシ基、ペンチ
ルオキシ基、デカンオキシ基、ドデカンオキシ基などを
挙げることができ、直鎖状でもよく、また分岐鎖状でも
よい。Specific examples of the alkyl group or alkoxy group represented by R in the above-mentioned formula (I) include a globyl group, a butyl group, a pentyl group, a hexyl group, an octyl group, a decyl group,
Examples include a pentyloxy group, a propoxy group, a butoxy group, a pentyloxy group, a decaneoxy group, a dodecaneoxy group, and the like may be linear or branched.
本発明に用いられる分離剤は多糖又はその誘導体を有効
成分とするものである。ここでいう多糖とは合成多糖、
天然多糖、天然物変成多糖のいずれかを問わず、光学活
性であればいかなるものでも良いが、好！シ〈は規則性
の高いホモグリカンでろゃ、しかも結合様式も一定であ
るものである。The separating agent used in the present invention contains a polysaccharide or a derivative thereof as an active ingredient. The polysaccharide referred to here is a synthetic polysaccharide,
Any optically active polysaccharide is fine, whether it is a natural polysaccharide or a naturally modified polysaccharide, but it is preferred! Shi〈 is a homoglycan with a high degree of regularity, and the bonding pattern is also constant.
更に好ｔＬ（は高純度の多糖を容易に得ることのできる
セルロース、アミロース、β−１，４−キトサン、キチ
ン、β−１，４−マンナン、β−１，４−キシラン、イ
ヌリン、α−１，３−グルカン、β−１，３−グルカン
等である。多糖の誘導体とは、上記多糖の有する水酸基
上の水素原子の一部あるいは全部、好１しくは８５％以
上を他の原子団で置換したものである。ここでいう原子
団は
であシ、Ｒ２は炭素数１乃至３よシ成る脂肪族基、３乃
至８よシ成る環式脂肪族基、炭素数４乃至２０よシ成る
芳香族基もしくはヘテロ芳香族基でろシ、いずれも置換
基を有しても良い。これらの誘導体は公知の各種の化学
反応を用いて容易に得ることができる。Furthermore, preferred tL (cellulose, amylose, β-1,4-chitosan, chitin, β-1,4-mannan, β-1,4-xylan, inulin, α- These include 1,3-glucan, β-1,3-glucan, etc. Polysaccharide derivatives refer to some or all, preferably 85% or more, of the hydrogen atoms on the hydroxyl groups of the polysaccharide to other atomic groups. R2 is an aliphatic group having 1 to 3 carbon atoms, a cycloaliphatic group having 3 to 8 carbon atoms, and a cycloaliphatic group having 4 to 20 carbon atoms. Any of the aromatic or heteroaromatic groups may have a substituent. These derivatives can be easily obtained using various known chemical reactions.
これら多糖又はその誘導体は分離剤の耐圧能力の向上、
溶媒置換による膨潤、収縮の防止、理論段数の向上のた
めに、担体に保持させることが好ましい。適当な担体の
太きとは使用するカラムの大きさによや変わるが、一般
に１μｍ〜１０ｍｍであシ、好筐しくに１μｍ〜３００
μｍである。担体は多孔質であることが好筐しく、平均
孔径は１０Ｘ〜１００＃ｒ！Ｉであシ、好ましくは５０
Ｘ〜１００００Ｘである。多糖又はその誘導体を保持さ
せる量は担体に対して１〜１００重食％、好！しくは５
〜５０重量％である。These polysaccharides or their derivatives improve the pressure resistance capacity of the separation agent,
In order to prevent swelling and shrinkage due to solvent substitution and to improve the number of theoretical plates, it is preferable to hold the carrier on a carrier. The appropriate thickness of the carrier varies depending on the size of the column used, but it is generally 1 μm to 10 mm, preferably 1 μm to 300 mm.
It is μm. The carrier is preferably porous, with an average pore size of 10X to 100 #r! I, preferably 50
X to 10,000X. The amount of polysaccharide or its derivative retained is preferably 1 to 100% based on the carrier! Or 5
~50% by weight.
多糖又はその誘導体を担体に保持させる方法は化学的方
法でも物理的方法でも良い。物理的方法としては、多糖
又はその誘導体を可溶性の溶剤に溶解させ、担体と良く
混合し、減圧又は加温下、気流によシ溶剤を留去させる
方法や、多糖又はその誘導体を可溶性の溶剤に溶解させ
、担体と良く混合した後、該溶剤と相溶性のない液体中
に攪はん、分散せしめ、該溶剤を拡散させる方法もある
。The method for retaining the polysaccharide or its derivative on the carrier may be either a chemical method or a physical method. Physical methods include dissolving the polysaccharide or its derivative in a soluble solvent, mixing well with the carrier, and distilling off the solvent with air flow under reduced pressure or heating; or dissolving the polysaccharide or its derivative in a soluble solvent. There is also a method in which the solvent is dispersed by dissolving it in a solvent, thoroughly mixing it with a carrier, and then stirring and dispersing it in a liquid that is incompatible with the solvent.
このようにして担体に保持した多糖又はその誘導体を結
晶化する場合には熱処理などの処理を行うことができる
。又、少量の溶剤を加えて多糖又はその誘導体を一旦膨
潤あるいは溶解せしめ、再び溶剤を留去することによシ
セの保持状態、ひいては分Ｓ能を変化せしめることが可
能である。When crystallizing the polysaccharide or its derivative held on the carrier in this way, a treatment such as heat treatment can be performed. Furthermore, by adding a small amount of solvent to once swell or dissolve the polysaccharide or its derivative, and then distilling off the solvent again, it is possible to change the state of retention of the liquid and thus the separation capacity.
担体としては、多孔質有機担体又は多孔質無機担体があ
シ、好筐しくは多孔質無機担体である。The carrier may be a porous organic carrier or a porous inorganic carrier, preferably a porous inorganic carrier.
多孔質有機担体として適轟なものは、ポリスチレン、ポ
リアクリルアミド、ポリアクリレート等から成る高分子
物質が挙げられる。多孔質無機担体として適当々ものは
シリカ、アルミナ、マグネシア、酸化チタン、ガラス、
ケイ酸塩、カオリンの如き合或若しくは天然の物質が挙
げられ多糖又はその誘導体との親和性を良くするために
表面処理を行っても良い。表面処理の方法としては、有
機シラン化合物を用いたシラン化処理やプラズマ重合に
よる表面処理法等がある。Suitable porous organic carriers include polymeric substances such as polystyrene, polyacrylamide, and polyacrylate. Suitable porous inorganic carriers include silica, alumina, magnesia, titanium oxide, glass,
Synthetic or natural substances such as silicates and kaolin may be used, and may be surface-treated to improve affinity with polysaccharides or derivatives thereof. Examples of surface treatment methods include silanization using an organic silane compound and surface treatment using plasma polymerization.
本発明は以上の如くであって、ラセミ体の原料から匍便
なりロマトグラフイーの技術によって医薬品、また合成
中間体として有用な光学活性欧１゜−パラ置換フェニル
エタノールを直接得る方法を穂立した。As described above, the present invention has established a method for directly obtaining optically active 1°-para-substituted phenylethanol, which is useful as a pharmaceutical or a synthetic intermediate, from racemic raw materials by chromatographic techniques. .
以下、実施例によって本発明を具体的に説明するが、本
発明がこれらに限定されるものでないことは言う１でも
ない。Hereinafter, the present invention will be specifically explained with reference to examples, but it is not to be said that the present invention is limited to these examples.
尚、実施例中で用いられる／ゼラメータに′及びαは以
下のように定義される。Incidentally, ' and α in the /zerameter used in the examples are defined as follows.
液体クロマトグラフィーを行う場合の溶離液としては、
該分離剤を溶解噴たはこれと反応する液体を除いて特に
制約はなく、また該分離剤を化学的方法で担体に結合し
たシ、架橋によシネ溶化した場合には反応性液体を除い
ては制約はないが、好筐しくは、ｎ−ヘキサンとテトラ
ヒドロフランの混合液が用いられる。いうまでもなく、
溶離液によって１−パラ置換フェニルエタノール光学異
性体の分離特性は変化するので、各種の展開溶媒を検討
することが望プしい。The eluent for liquid chromatography is
There are no particular restrictions other than the liquid that dissolves or reacts with the separating agent, and if the separating agent is bonded to a carrier by a chemical method or cine-solubilized by crosslinking, the reactive liquid may be excluded. Although there are no restrictions, preferably a mixture of n-hexane and tetrahydrofuran is used. Needless to say,
Since the separation characteristics of 1-para-substituted phenylethanol optical isomers change depending on the eluent, it is desirable to consider various developing solvents.
（実施例）
１−ノぐライソプチルフエニルエタノールノエナンチオ
マ−の汎金物を、セルロース３，５ジメチルフエニルカ
ルバメートをゾフェニルシツン処ｌまたシリカダルに約
２０重量％になるように担持した分離剤を充填した長さ
２５ｃｍ５内径０．４６ｃｒｓのステンレスカラムを液
体クロマトグラフィー用カラムとして、溶離液：ｎ−ヘ
キサン／テトラヒドロフラン（Ｉ９：１）、温度２５℃
、流速１．０１１７／ｍ１ｎＯ条件で光学分割した。溶
離した光学異性体の検出は紫外検知器で波長２５４ ｎ
ｍの紫外吸収を用いて折々りた。３体及び８体の決定は
、分取して施光度を測定することによシ行なった。(Example) A pan-metallic material of 1-lysoptylphenylethanol noenantiomer was treated with cellulose 3,5 dimethyl phenyl carbamate using zophenyl silica or a separating agent supported on silica dal at a concentration of about 20% by weight. A packed stainless steel column with a length of 25 cm and an internal diameter of 0.46 crs was used as a liquid chromatography column, eluent: n-hexane/tetrahydrofuran (I9:1), temperature 25°C.
, the optical resolution was carried out under conditions of a flow rate of 1.0117/m1nO. The eluted optical isomer was detected using an ultraviolet detector at a wavelength of 254 nm.
Folded using ultraviolet absorption of m. The determination of 3 and 8 bodies was carried out by fractionating and measuring the intensity of light exposure.
その結果、３体と８体の保持時間はそれぞれ１１．９分
と１３．５分であシ、Ｒ体及び８体の容量比及び分離係
数は以下の通シであった。As a result, the retention times for the 3-body and 8-body were 11.9 minutes and 13.5 minutes, respectively, and the capacity ratios and separation coefficients for the R-body and the 8-body were as follows.
Claims (1)
コキシ基を示す。＊は不斉炭素原子を示す。）で示され
る１−パラ置換フェニルエタノールのエナンチオマーの
混合物をそのまま直接、多糖又はその誘導体を有効成分
とする分離剤によって液体クロマトグラフィーにより光
学分割することを特徴とする１−パラ置換フェニルエタ
ノールの光学分割方法。 ２、分離剤として、セルロース−３，５−ジメチルフェ
リルカルバメートを有効成分としたものを用いる請求項
１記載の光学分割方法。 ３、分離剤として、セルロース−４−メチルフェニルカ
ルバメートを有効成分としたものを用いる請求項１記載
の光学分割方法。 ４、分離剤として、セルロース−４−メチルベンゾエー
トを有効成分としたものを用いる請求項１記載の光学分
割方法。 ５、１−パラ置換フェニルエタノールが１−パライソブ
チルフェニルエタノールである請求項２〜３のいずれか
１項記載の光学分割方法。[Claims] 1. General formula (I) ▲There are numerical formulas, chemical formulas, tables, etc.▼...(I) (In the formula, R represents an alkyl group or an alkoxy group having 3 to 20 carbon atoms. 1-, which is characterized in that a mixture of enantiomers of 1-para-substituted phenylethanol represented by (indicates a stereogenic carbon atom) is directly optically resolved as it is by liquid chromatography using a separation agent containing a polysaccharide or a derivative thereof as an active ingredient. Optical resolution method for para-substituted phenylethanol. 2. The optical resolution method according to claim 1, wherein the separating agent contains cellulose-3,5-dimethylferyl carbamate as an active ingredient. 3. The optical resolution method according to claim 1, wherein the separating agent contains cellulose-4-methylphenylcarbamate as an active ingredient. 4. The optical resolution method according to claim 1, wherein the separating agent contains cellulose-4-methylbenzoate as an active ingredient. 4. The optical resolution method according to claim 2, wherein the 5,1-para-substituted phenylethanol is 1-para-isobutylphenylethanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP32095589A JPH03181433A (en) | 1989-12-11 | 1989-12-11 | Direct resolution for 1-p-substituted phenylethanol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP32095589A JPH03181433A (en) | 1989-12-11 | 1989-12-11 | Direct resolution for 1-p-substituted phenylethanol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03181433A true JPH03181433A (en) | 1991-08-07 |
Family
ID=18127160
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP32095589A Pending JPH03181433A (en) | 1989-12-11 | 1989-12-11 | Direct resolution for 1-p-substituted phenylethanol |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03181433A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3296735A4 (en) * | 2015-05-14 | 2018-05-30 | Daicel Corporation | Separating agent for optical isomers |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61176538A (en) * | 1985-02-01 | 1986-08-08 | Daicel Chem Ind Ltd | Optical resolution of aralkyl alcohol |
| JPH02127401A (en) * | 1988-11-07 | 1990-05-16 | Nippon Steel Corp | Packing agent for separation of optical isomer |
-
1989
- 1989-12-11 JP JP32095589A patent/JPH03181433A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61176538A (en) * | 1985-02-01 | 1986-08-08 | Daicel Chem Ind Ltd | Optical resolution of aralkyl alcohol |
| JPH02127401A (en) * | 1988-11-07 | 1990-05-16 | Nippon Steel Corp | Packing agent for separation of optical isomer |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3296735A4 (en) * | 2015-05-14 | 2018-05-30 | Daicel Corporation | Separating agent for optical isomers |
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