JPH02225451A - 2'-ketopantothenic ester - Google Patents
2'-ketopantothenic esterInfo
- Publication number
- JPH02225451A JPH02225451A JP4540789A JP4540789A JPH02225451A JP H02225451 A JPH02225451 A JP H02225451A JP 4540789 A JP4540789 A JP 4540789A JP 4540789 A JP4540789 A JP 4540789A JP H02225451 A JPH02225451 A JP H02225451A
- Authority
- JP
- Japan
- Prior art keywords
- ester
- ketopantothenic
- formula
- acid
- pantothenic
- 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.)
- Granted
Links
- 150000002148 esters Chemical class 0.000 title abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 16
- -1 D-pantothenic acid ester Chemical class 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- 239000000126 substance Substances 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 6
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 abstract description 6
- 238000006243 chemical reaction Methods 0.000 abstract description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 abstract description 6
- HRTOQFBQOFIFEE-UHFFFAOYSA-N 2-dehydropantolactone Chemical compound CC1(C)COC(=O)C1=O HRTOQFBQOFIFEE-UHFFFAOYSA-N 0.000 abstract description 3
- 238000009835 boiling Methods 0.000 abstract description 3
- 244000005700 microbiome Species 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 abstract description 3
- 229940000635 beta-alanine Drugs 0.000 abstract description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-aminopropionic acid Natural products NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 150000004702 methyl esters Chemical class 0.000 abstract description 2
- 230000035484 reaction time Effects 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract 2
- GHOKWGTUZJEAQD-SSDOTTSWSA-N 3-[[(2s)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]propanoic acid Chemical class OCC(C)(C)[C@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-SSDOTTSWSA-N 0.000 abstract 1
- 238000007098 aminolysis reaction Methods 0.000 abstract 1
- 239000012279 sodium borohydride Substances 0.000 abstract 1
- 229910000033 sodium borohydride Inorganic materials 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229940055726 pantothenic acid Drugs 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N pantothenic acid Natural products OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- 235000019161 pantothenic acid Nutrition 0.000 description 2
- 239000011713 pantothenic acid Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- FRHWYVGCFUQMJR-UHFFFAOYSA-N benzyl 3-aminopropanoate;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.NCCC(=O)OCC1=CC=CC=C1 FRHWYVGCFUQMJR-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- MQRJBSHKWOFOGF-UHFFFAOYSA-L disodium;carbonate;hydrate Chemical compound O.[Na+].[Na+].[O-]C([O-])=O MQRJBSHKWOFOGF-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- RJCGNNHKSNIUAT-UHFFFAOYSA-N ethyl 3-aminopropanoate;hydron;chloride Chemical compound Cl.CCOC(=O)CCN RJCGNNHKSNIUAT-UHFFFAOYSA-N 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- XPGRZDJXVKFLHQ-UHFFFAOYSA-N hydron;methyl 3-aminopropanoate;chloride Chemical compound Cl.COC(=O)CCN XPGRZDJXVKFLHQ-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- QDQVXVRZVCTVHE-YFKPBYRVSA-N propan-2-yl (2s)-2-aminopropanoate Chemical compound CC(C)OC(=O)[C@H](C)N QDQVXVRZVCTVHE-YFKPBYRVSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、医薬として、また生理学的に重要な物質であ
るビタミンとして有用なり一バントテン酸の新規な合成
用中間体に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a novel intermediate for the synthesis of monobantothenic acid, which is useful as a medicine and as a physiologically important substance, a vitamin.
さらに詳しく言えば、本発明は、式
％式％（）
（式中、Ｒはアルキル基又はアラルキル基を示す）
で示される新規化合物、２′−ケトパントテン酸エステ
ル、すなわち、Ｎ−（２−Ｒオキシカルボニルエチル）
−４−ヒドロキシ−３，３−ジメチル−２−オキソブチ
ルアミドを提供するものである。More specifically, the present invention provides a novel compound represented by the formula % (in which R represents an alkyl group or an aralkyl group), a 2'-ketopantothenic acid ester, i.e., N-(2- Roxycarbonylethyl)
-4-hydroxy-3,3-dimethyl-2-oxobutyramide.
本発明に係る新規物質、２′−ケトパントテン酸エステ
ルは、Ｄ−パントテン酸エステルのプロキラル体であり
、このものを原料として、−般的なカルボニル還元試薬
であるＮａＢＨ，等を用いて還元反応を行なうとり、Ｌ
−パントテン酸エステルが得られ、また、微生物により
不斉還元反応を行なわせるとＤ−パントテン酸エステル
を得ることができるので、Ｄ、Ｌ−パントテン酸エステ
ル特に、Ｄ−パントテン酸エステル製造のための折中間
体物質として極めて有用なものである。The new substance according to the present invention, 2'-ketopantothenic acid ester, is a prochiral form of D-pantothenic acid ester, and using this substance as a raw material, a reduction reaction is carried out using a general carbonyl reducing reagent such as NaBH. To do this, L
-D-pantothenic acid ester can be obtained, and D-pantothenic acid ester can be obtained by performing an asymmetric reduction reaction using microorganisms. It is extremely useful as a folding intermediate material.
〔発明の開示１
本発明に係る２′−ケトパントテン酸エステルは、ケト
バントラクトンとβ−アラニンエステルとを用いてアミ
ツリシスを行なわせることにより、得ることができる。[Disclosure 1 of the Invention The 2'-ketopantothenic acid ester according to the present invention can be obtained by performing amitrisis using ketobantolactone and β-alanine ester.
この反応においては、反応溶媒としては、メタノール等
のアルコール、酢酸エチル等のエステル類、ヘキサン等
の脂肪族炭化水素、ベンゼン等の芳香族炭化水素、クロ
ロホルム等のハロゲン化炭化水素５、アセトン等のケト
ン類、アセトニトリル等が使用される。その際の反応温
度は室温から各反応溶媒の煮沸温度程度までの範囲内で
あり、反応時間は通常、１時間から１日である。反応終
了後、反応溶媒を留去し、酢酸エチルや塩化メチレン等
の有機溶媒で目的物の抽出を行なう。必要に応じ、希酸
水溶液や希アルカリ水溶液で洗浄を行なう。かくして、
好収率で、単一の２′−ケトパントテン酸エステルが得
られる。In this reaction, reaction solvents include alcohols such as methanol, esters such as ethyl acetate, aliphatic hydrocarbons such as hexane, aromatic hydrocarbons such as benzene, halogenated hydrocarbons such as chloroform, and acetone. Ketones, acetonitrile, etc. are used. The reaction temperature at that time is within a range from room temperature to about the boiling temperature of each reaction solvent, and the reaction time is usually from 1 hour to 1 day. After the reaction is completed, the reaction solvent is distilled off, and the target product is extracted with an organic solvent such as ethyl acetate or methylene chloride. If necessary, clean with a dilute acid aqueous solution or dilute alkali aqueous solution. Thus,
A single 2'-ketopantothenic acid ester is obtained in good yield.
以下に実施例を掲げ、本発明を更に具体的に説明するが
、本発明はこれら実施例に限定されるものではない。The present invention will be described in more detail with reference to Examples below, but the present invention is not limited to these Examples.
実施例 １
２′−ケトパントテン酸メチルエステルの製造金属ナト
リウム１．２ｇ（５２ａモル）を無水メタノール２００
ｍｇに溶解し、これに室温下で、β−アラニンメチルエ
ステル塩酸塩７−３９（５２１１モル）およびケトパン
トラクトン６．４９（５０１１モル）をその順序で加え
る。室温にて一晩撹拌した後、メタノールを留去する。Example 1 Preparation of 2'-ketopantothenic acid methyl ester 1.2 g (52 a mol) of sodium metal was added to 200 g of anhydrous methanol.
β-alanine methyl ester hydrochloride 7-39 (5211 mol) and ketopantolactone 6.49 (5011 mol) are added in that order at room temperature. After stirring overnight at room temperature, methanol is distilled off.
副生じた塩化ナトリウムを含む反応混合物を水に溶解し
、酢酸エチルで抽出する。酢酸エチル層を無水硫酸ナト
リウムで乾燥した後、減圧濃縮し、シリカゲルによるカ
ラムクロマト精製を行なうと、２′−ケトパントテン酸
メチルエステル１０．１ｇ（収率： ８７．３％）がｏ
ｉｌとして得られた。The reaction mixture containing by-produced sodium chloride is dissolved in water and extracted with ethyl acetate. After drying the ethyl acetate layer over anhydrous sodium sulfate, it was concentrated under reduced pressure and purified by column chromatography using silica gel.
Obtained as il.
ＩＲ（ｎｅａｔ）ｙｃｍ−’： ３３８（Ｌ ２９５
５．２８７５． １７４０゜１７１５、 １６８０．
１５１５． １４２０゜１３７０、 １２６０． １２
００． １１８０゜’Ｈ−ＮＭＩ？（ＣＤＣＩ２Ｓ）δ
： １．２８ （６Ｈ，Ｓ）２．５７ （２Ｈ，ｔ）
３．５８ （２Ｂ、 ｑ）
３．７２ （５Ｈ，ｓ）
７．５ （ＩＨ，ｂｓ）
実施例 ２
２′−ケトパントテン酸エチルエステルの製造ソジウム
エトキシド３．６９（５２，５１モル）を無水エタノー
ル１５（ｈ＋＋２に溶解し、これに、β−アラニンエチ
ルエステル塩酸塩８−１ｇ（５２，５１１モル）および
ケトパントラクトン６．４９（５０ｍモル）をその順序
で加える。室温にて一晩撹拌した後、エタノールを留去
する。エタノールの留去後は、実施例１におけるメタノ
ール留去後と同様の操作を行ない、２′−ケトパントテ
ン酸エチルエステルを１０．８ｇ（収率： ８８．１％
）をｏｉｌとして得た。IR(neat)ycm-': 338(L 295
5.2875. 1740°1715, 1680.
1515. 1420°1370, 1260. 12
00. 1180°'H-NMI? (CDCI2S)δ
: 1.28 (6H, S) 2.57 (2H, t) 3.58 (2B, q) 3.72 (5H, s) 7.5 (IH, bs) Example 2 2'-ketopantothenic acid Preparation of ethyl ester 3.69 (52,51 mol) of sodium ethoxide is dissolved in 15 (h++2) of absolute ethanol, and 8-1 g (52,511 mol) of β-alanine ethyl ester hydrochloride and ketopantolactone are dissolved in 15 (h++2) of absolute ethanol. Add 6.49 (50 mmol) in that order. After stirring overnight at room temperature, ethanol is distilled off. After distilling off ethanol, perform the same operation as after distilling off methanol in Example 1, 10.8g of 2'-ketopantothenic acid ethyl ester (yield: 88.1%)
) was obtained as oil.
ＩＲ（ｎｅａｔ）ｙ ｃｍ−” ： ３３８０．２９８
０．２９４５．２８７５゜１７３５、１６８０． １５
２５． １４８０゜１３８０、１１９０．１１００．１
０５０’Ｈ−Ｎ＆１Ｒ（ＣＤＣａ３）δ： １．２８
（６Ｈ，ｓ）１．２８ （３Ｈ，ｔ）
２．５７ （２Ｈ，ｔ）
３．５８ （２Ｈ，Ｑ）
３．７５ （２Ｈ，ｓ）
４．１８ （２Ｈ，ｑ）
７．５ （１，Ｈ，ｂｓ）
実施例 ３
２′−ケトパントテン酸イソプロピルエステルの製造
ソジウムエトキシド３．６ｙ（５２−５ｍモル）を無水
イソプロパツール１５０ｍ１２に溶解し、これに、β−
アラニンイソプロピルエステルａＫ 酸塩８ 、８９（
５２，５＋モル）およびケトバントラクトン６．４ｇ（
５０ｍモル）をその順序で加える。室温にて一晩撹拌し
た後、インプロパツールを留去する。インプロパツール
の留去後は実施例１におけるメタノール留去後と同様の
操作を行なって、２′−ケトパントテン酸イソプロピル
エステルｌｔ、３ｇ（収率： ８７．２％）をｏｉｌと
して得た。IR(neat)y cm-”: 3380.298
0.2945.2875°1735, 1680. 15
25. 1480°1380, 1190.1100.1
050′H-N&1R(CDCa3)δ: 1.28
(6H,s) 1.28 (3H,t) 2.57 (2H,t) 3.58 (2H,Q) 3.75 (2H,s) 4.18 (2H,q) 7.5 (1 .
Alanine isopropyl ester aK acid salt 8, 89 (
52,5+ mol) and 6.4 g of ketobantolactone (
50 mmol) are added in that order. After stirring overnight at room temperature, the Impropatool is distilled off. After the impropatol was distilled off, the same operation as after methanol distillation in Example 1 was performed to obtain 3 g (yield: 87.2%) of 2'-ketopantothenic acid isopropyl ester lt as oil.
ＩＲ（ｎｅａｔ）シｃｒａ−’ ＋ ３３８０．２９８
０．２９４０．２８？５゜１７３０、 １６８０． １
５２５． １４７５．１３８０、 １２７０． １２０
０． １１０５゜’Ｈ−ＮＭＲ（ＣＤＣＬ）δ： １．
２８ （６Ｈ，ｓ）１．２５ （６Ｈ，ｄ）
２．５４ （２Ｈ，ｔ）
３．５７ （２Ｈ，ｑ）
３．７５ （２Ｈ，ａ）
５．０４ （ＩＨ，ｑｑ）
７．２９ （ＩＨ，ｂｓ）
実施例 ４
２′−ケトパン）・テン酸ベンジルエステルの製造
β−アラニンベンジルエステル−ｐ−トルエンスルホン
酸塩３−５ｇ（１０ｍモル）を１０％炭酸ソーダ水に溶
解し、酢酸エチルで抽出する。この酢酸エチル層を無水
硫酸マグネシウムで乾燥した後、減圧濃縮する。残留物
を、無水メタノールに溶解し、これに、ケトバントラク
トン１．３ｇ（１０＋ａモル）を加え、６時間、還流煮
沸した後、メタノールを留去する。メタノール留去後は
、実施例１におけるメタノール留去後と同様の操作を行
なって、２′−ケトパントテン酸ベンジルエステル１．
６９（収率：５２％）をｏｉｌとして得た。IR (neat) shicra-' + 3380.298
0.2940.28?5゜1730, 1680. 1
525. 1475.1380, 1270. 120
0. 1105°'H-NMR (CDCL) δ: 1.
28 (6H, s) 1.25 (6H, d) 2.54 (2H, t) 3.57 (2H, q) 3.75 (2H, a) 5.04 (IH, qq) 7.29 ( IH, bs) Example 4 Production of benzyl thenic acid (2'-ketopane) 3-5 g (10 mmol) of β-alanine benzyl ester p-toluenesulfonate was dissolved in 10% sodium carbonate water, and dissolved in ethyl acetate. Extract with This ethyl acetate layer is dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue is dissolved in anhydrous methanol, 1.3 g (10+a mol) of ketobantolactone are added thereto, and after boiling under reflux for 6 hours, the methanol is distilled off. After methanol distillation, the same operation as after methanol distillation in Example 1 was performed to obtain 2'-ketopantothenic acid benzyl ester 1.
69 (yield: 52%) was obtained as oil.
ＩＲ（ｎｅａｔ）ｙ ｃｒａ−’ ： ３４００． ２
９７５．２９４０．２８７５゜１？３５． １６８０．
１５２０． １４７５゜１４６０、 １３９０． １
３６０． １２６０゜１１８０、１１０５．１０５０
’Ｈ−ＮＭＲ（ＣＤＣＩ２ｘ）δ： １．２６ （６Ｈ
，ｓ）２．６２ （２Ｈ，ｔ）
３．５８ （２Ｈ，ｑ）
３．７３ （２Ｂ、 ｓ）
５．１４ （２Ｈ，ｓ）
７．３５ （５Ｈ，ｓ）
本発明に係る２′−ケトパントテン酸エステルを使用し
、微生物により不斉還元を行なわせ、Ｄ−パントテン酸
エステルを製造する例を以下に参考例として掲げる。IR(neat)ycra-': 3400. 2
975.2940.2875゜1?35. 1680.
1520. 1475°1460, 1390. 1
360. 1260°1180, 1105.1050'H-NMR (CDCI2x) δ: 1.26 (6H
, s) 2.62 (2H, t) 3.58 (2H, q) 3.73 (2B, s) 5.14 (2H, s) 7.35 (5H, s) 2'- An example in which a D-pantothenic acid ester is produced by using a ketopantothenic acid ester and performing asymmetric reduction using a microorganism is listed below as a reference example.
参考例 １〜６
グルツース５％、コーンステイープリカー５％、炭酸カ
ルシウム１％からなる液体培地（ｐＨ７，０）を６つの
試験管に２１ＩＱずつ分注し、オートクレーブ中で１２
１℃で２０分間、加熱滅菌した。Reference Examples 1 to 6 A liquid medium (pH 7.0) consisting of 5% glucose, 5% cornstarch liquor, and 1% calcium carbonate was dispensed into 6 test tubes at 21 IQ, and 12 IQ was placed in an autoclave.
Heat sterilization was performed at 1° C. for 20 minutes.
各試験管内の培地に、斜面培地から第１表に記載した各
種の菌株を１白金耳量ずつとり、接種し、２８℃で２日
間、好気的に振盪培養した。この各試験管内の培養液に
対し、２′−ケトパントテン酸エチルエステルを２０謂
９ずつ加え、２８°Ｃで２日間振盪した。反応後、ＨＰ
ＬＣ（Ｃｏｓｍｏｓｉ１５Ｃｒａ １４．６ Ｘ
Ｑ ｌｏｏ＋ｌＩｍ、溶離液３０％メタノール（ｐＨ
２，５） 、流速１ ｒｓ（１／ １１１ｉｎ、検出波
長２３０ｎｍ）にて各試験管におけるパントテン酸エチ
ルエステルの生成量を測定した。更に、反応液より、酢
酸エチルを用いてパントテン酸エチルエステルを抽出し
、塩酸で加水分解した後、生成したバントラクトンの光
学純度をＧＬＣ（ＡｎａｌｙｔｉｃａｌＢｉｏｃｈｅｍ
ｉｓｔｒｙ、 １１２． ９−１６ （１９８１））
にて測定した。その結果は第１表に示す通りである。One platinum loopful of each strain listed in Table 1 was taken from the slant medium and inoculated into the medium in each test tube, and cultured aerobically with shaking at 28° C. for 2 days. Twenty or nine portions of 2'-ketopantothenic acid ethyl ester were added to the culture solution in each test tube, and the mixture was shaken at 28°C for 2 days. After reaction, HP
LC(Cosmosi15Cra 14.6X
Q loo+lIm, eluent 30% methanol (pH
2,5), the amount of pantothenic acid ethyl ester produced in each test tube was measured at a flow rate of 1 rs (1/111 inch, detection wavelength 230 nm). Furthermore, pantothenic acid ethyl ester was extracted from the reaction solution using ethyl acetate and hydrolyzed with hydrochloric acid.
istry, 112. 9-16 (1981))
Measured at The results are shown in Table 1.
第１表中、ＩＦＯＮｏ−は、財団法人醗酵研究所カタロ
グ番号を示′し、ＩＡＭ Ｎｏ、は、東京大学応用微生
物研究所カタログ番号を示す。In Table 1, IFO No. indicates the catalog number of the Fermentation Research Institute, and IAM No. indicates the catalog number of the Institute of Applied Microbiology, the University of Tokyo.
Claims (5)
に記載の化合物。(2) Claim 1, wherein R in the above formula (I) is a methyl group.
Compounds described in.
に記載の化合物。(3) Claim 1, wherein R in the above formula (I) is an ethyl group.
Compounds described in.
求項１に記載の化合物。(4) The compound according to claim 1, wherein R in the above formula (I) is an isopropyl group.
１に記載の化合物。(5) The compound according to claim 1, wherein R in the above formula (I) is a benzyl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4540789A JP2609922B2 (en) | 1989-02-28 | 1989-02-28 | 2'-Ketopantothenic acid ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4540789A JP2609922B2 (en) | 1989-02-28 | 1989-02-28 | 2'-Ketopantothenic acid ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02225451A true JPH02225451A (en) | 1990-09-07 |
| JP2609922B2 JP2609922B2 (en) | 1997-05-14 |
Family
ID=12718400
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4540789A Expired - Fee Related JP2609922B2 (en) | 1989-02-28 | 1989-02-28 | 2'-Ketopantothenic acid ester |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2609922B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0748792A4 (en) * | 1994-03-02 | 1996-11-11 | Tovarischestvo S Ogranichennoi | Calcium ketopantothenate with acetylating properties |
-
1989
- 1989-02-28 JP JP4540789A patent/JP2609922B2/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0748792A4 (en) * | 1994-03-02 | 1996-11-11 | Tovarischestvo S Ogranichennoi | Calcium ketopantothenate with acetylating properties |
| EP0748792A1 (en) * | 1994-03-02 | 1996-12-18 | Tovarischestvo S Ogranichennoi Otvetstvennostju " Pant" | Calcium ketopantothenate with acetylating properties |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2609922B2 (en) | 1997-05-14 |
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