WO1995014032A1 - Process for producing 25-hydroxylated cholesterol - Google Patents
Process for producing 25-hydroxylated cholesterol Download PDFInfo
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- WO1995014032A1 WO1995014032A1 PCT/JP1994/001937 JP9401937W WO9514032A1 WO 1995014032 A1 WO1995014032 A1 WO 1995014032A1 JP 9401937 W JP9401937 W JP 9401937W WO 9514032 A1 WO9514032 A1 WO 9514032A1
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- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
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- the present invention relates to a method for hydroxylating cholesterols at the 25-position. More specifically, the present invention relates to a reaction using a ruthenium compound as a catalyst in an oxidation reaction for introducing a hydroxyl group into the 25-position of cholesterol.
- vitamin D 3 such as osteoporosis therapeutic agents are synthesized from cholesterol, and the like. Active form of vitamin D 3 compounds have a hydroxyl group at the 2 position 5, but in order to introduce hydroxyl groups into two 5-position, the reaction many problems as described above is that not remain There is a need to do.
- the present invention solves these industrial problems by (1) ensuring cheap and large amounts of starting materials, (2) significantly shortening the manufacturing process, (3) avoiding the use of highly toxic and dangerous chemicals, and (4) anhydrous conditions. improvement of avoiding such operability, 5 a significant reduction in manufacturing equipment by shortening the process, it is intended to cane attainable and 6 inevitable manufacturing costs Bok reduction of P
- the present inventors have introduced inexpensive and large quantities.
- Various methods for the production of 25-hydroxylated product using cholesterol as a starting material were studied.
- the cholestanol derivative saturated with the double bond of cholesterol is hydroxylated by an oxidation system using a co-oxidant using a ruthenium compound as a catalyst, so that the 25-position hydroxylated product can be directly and highly selectively formed.
- Starting materials such as cholesterols having a hydrogen atom at the 25-position include cholesterol double bond-saturated compounds (for example, cholestanol ⁇ coprostanol) and cholesterol double bonds that are oxidatively stable protecting groups.
- a bromine adduct of cholesterol a compound in which the hydroxyl group at position 3 of these compounds is protected with a protecting group such as an acetyl group (eg, acetyl cholesterol, acetyl propyl prostanol), (Eg, cholestanone, coprostanone).
- these compounds may have a substituent or a functional group (for example, an acetyl group or a halogen atom) which is stable to oxidation.
- Preferable examples of cholesterol include cholesterol, coprostanol, acetylcholethanol, acetylcoprostanol, cholestanone, coprosylnon, and the like. can give.
- An example of a preferred embodiment of the present invention is to convert a cholesterol to a cholestanol derivative by saturating the double bond at the 5-position by a conventional method, and then protecting or oxidizing a hydroxyl group as necessary.
- a ruthenium compound is used as a catalyst to perform oxidation using an oxidation system using a co-oxidant such as periodic acid. This is shown in the equation.
- the product obtained here is optional.
- the ruthenium compound means a ruthenium salt or ruthenium oxide, preferably a compound such as ruthenium trichloride, ruthenium dioxide or ruthenium tetroxide.
- the amount of the catalyst used in the reaction varies depending on the starting compounds, reaction conditions, and the like, but is preferably 1 mol% to 50 mol%, more preferably 1 mol% to 10 mol%.
- the co-oxidizing agent means an inorganic oxidizing agent such as periodates and hypochlorites, and an organic oxidizing agent such as morpholinoxide. These oxidizing agents are inexpensive and stable. It forms an oxidation reaction system with the catalyst.
- Solvents used in this reaction include water and saturated hydrocarbons, ketones, esters, halogenated hydrocarbons that are stable under oxidizing conditions such as hexane, butanone, ethyl acetate, carbon tetrachloride or dichloromethane.
- the mixture is desirably carried out in a two-phase solvent system in the presence or absence of a solvent such as acetonitrile.
- This reaction is carried out at 10 ° C to 80 ° C, preferably at 20 ° C to 50 ° C.
- the reaction time of this reaction can be selected according to the progress of the reaction by tracking the reaction with thin layer chromatography, high performance liquid chromatography, or the like.
- the 25-hydroxylated product of the target compound can be isolated and purified by ordinary means after collecting the target product in the organic layer by solvent extraction from the reaction solution itself or by adding a new appropriate solvent. S o.
- Example 2 The same reaction and operation as in Example 1 were performed using 3.87 g of 5 ⁇ -cholestan-3-one in place of cholestanol in Example 1. Yield 1.05 g, 26% yield.
- the present invention relates to the industrial production of the 25-hydroxylated cholesterol, which is useful as an intermediate for the production of pharmaceuticals, by (1) securing inexpensive and large quantities of starting materials, (2) significantly reducing the production process, and (3) toxicity and danger. It is possible to avoid the use of highly expensive chemicals, ⁇ improve operability such as avoiding anhydrous conditions, 5 drastically reduce manufacturing equipment by shortening the process, 6 reduce inevitable manufacturing costs.
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Abstract
A process for producing a 25-hydroxycholesterol by hydroxylating a cholesterol at the 25-position using a ruthenium compound as a catalyst. This process is an industrial process for producing a 25-hydroxylated cholesterol useful as an intermediate for producing drugs and makes it possible (1) to secure the starting material in a large quantity at a low cost, (2) to shorten extremely the production steps, (3) to avoid the use of highly toxic or dangerous chemicals, (4) to improve the workability by, for example, evading employing an anhydrous condition, (5) to curtail remarkably the production facilities by shortening the production steps, and (6) to reduce the necessary production cost.
Description
明 細 書 Specification
コレステロール類の 2 5位水酸化体の製造方法 Method for producing 25-hydroxylated cholesterol
技術分野 Technical field
本発明は、 コレステロール類の 2 5位の水酸化方法に関する。 さらに詳しくは、 コレステロール類の 2 5位に水酸基を導入する酸化反応において、 触媒としてル チニゥム化合物を用いる反応に関する。 本発明の方法により製造される化合物は、 骨粗鬆症治療薬であるビタミン D 3等の医薬品などの合成中間体として有用であ る。 The present invention relates to a method for hydroxylating cholesterols at the 25-position. More specifically, the present invention relates to a reaction using a ruthenium compound as a catalyst in an oxidation reaction for introducing a hydroxyl group into the 25-position of cholesterol. Compounds prepared by the process of the present invention, Ru useful der as synthetic intermediates, such as pharmaceuticals vitamin D 3 such as a therapeutic agent for osteoporosis.
背景技術 Background art
コレステロール類の 2 5位の水酸化体の優れた合成方法として、 例えば特公昭 6 1— 4 4 8 7 9号に記載される方法等があげられる。 しかし、 これらの従来の 2 5位水酸化体の合成法には、 ①出発原料が高価である、 ②大量の取扱いには著 しく危険性の高い試薬を使用する、 ③毒性の高い試薬を使用する、 ④多くの無水 条件が存在する、 ⑤工程数が長い、 ⑥収率が低いなどの工業的に不利な点が多く 残されている。 また、 最近のコレステロール類の 2 5位の水酸化体の合成法とし て』. O r g . C h e m. , 1 9 9 2 , 5 7， 5 0 5 2に記載される方法がある。 しかし、 この方法は極めて危険性の高い試薬であるジメチルジォキシランまたは さらに危険性の高いメチルトリフルォロジメチルジォキシランを酸化剤に用いる もので、 0：業的に適用することは殆ど不可能である。 As an excellent method for synthesizing the hydroxylated compound at position 25 of cholesterols, for example, the method described in JP-B-61-44879 can be mentioned. However, these conventional methods for synthesizing the hydroxylated 25-position include: (1) starting materials are expensive; (2) use extremely dangerous reagents for large-scale handling; and (3) use highly toxic reagents. ④ There are many industrial disadvantages such as 無水 many anhydrous conditions, 長 い long number of steps, ⑥ low yield. Also, as a recent method for synthesizing the hydroxylated compound at position 25 of cholesterols, there is a method described in Org. Chem., 1992, 57, 5502. However, this method uses dimethyldioxylan, which is a very dangerous reagent, or methyltrifluoromethyldioxylan, which is even more dangerous, as an oxidizing agent. 0: It is hardly applied industrially. It is possible.
骨粗鬆症治療薬であるビタミン D 3等の医薬品はコレステロール類等から合成 される。 活性型のビタミン D 3化合物はその 2 5位に水酸基を有しているが、 2 5位に水酸基を導入するためには、 先に述べたような多くの問題点が残されてい る反応を行う必要がある。 Pharmaceutical vitamin D 3 such as osteoporosis therapeutic agents are synthesized from cholesterol, and the like. Active form of vitamin D 3 compounds have a hydroxyl group at the 2 position 5, but in order to introduce hydroxyl groups into two 5-position, the reaction many problems as described above is that not remain There is a need to do.
本発明は、 これらの工業上の諸問題を解決し、 ①出発物質の安価かつ大量な確 保、 ②製造工程の大幅な短縮、 ③毒性や危険性の高い薬品の使用の回避、 ④無水 条件の回避など操作性の向上、 ⑤工程短縮による製造設備の大幅な削減、 ⑥必然 的な製造コス卜の低減などを達成可能にしょうとするものである P The present invention solves these industrial problems by (1) ensuring cheap and large amounts of starting materials, (2) significantly shortening the manufacturing process, (3) avoiding the use of highly toxic and dangerous chemicals, and (4) anhydrous conditions. improvement of avoiding such operability, ⑤ a significant reduction in manufacturing equipment by shortening the process, it is intended to cane attainable and ⑥ inevitable manufacturing costs Bok reduction of P
発明の開示 Disclosure of the invention
本発明者らは従来の技術の工業上の問題点を解決するため、 安価かつ大量に入
手可能なコレステロールを出発原料とする 2 5位水酸化体の製法を種々検討した。 その結果、 コレステロール類の二重結合を飽和したコレスタノール誘導体をルテ ニゥム化合物を触媒とし、 共酸化剤を用いる酸化系により水酸化することにより、 直接かつ高選択的に 2 5位水酸化体が合成できることを見いだした。 To solve the industrial problems of the conventional technology, the present inventors have introduced inexpensive and large quantities. Various methods for the production of 25-hydroxylated product using cholesterol as a starting material were studied. As a result, the cholestanol derivative saturated with the double bond of cholesterol is hydroxylated by an oxidation system using a co-oxidant using a ruthenium compound as a catalyst, so that the 25-position hydroxylated product can be directly and highly selectively formed. We found that we could combine.
出発物質である 2 5位に水素原子を有するコレステロール類には、 コレステロ ールの二重結合を飽和した化合物 （例えば、 コレスタノールゃコプロスタノール） 、 コレステロールの二重結合を酸化に安定な保護基で保護した化合物 （例えばコ レステロールの臭素付加体） 、 これらの化合物の 3位の水酸基をァシル基等の保 護基で保護した化合物 （例えば、 ァセチルコレス夕ノール、 ァセチルコプロスタ ノール） 、 3位の水酸基を酸化した化合物 （例えば、 コレスタノン、 コプロスタ ノン） 等が含まれる。 またこれらの化合物は酸化に安定な置換基や官能基 （例え ば、 ァセトキシ基ゃハロゲン原子等） を有していてもよい。 コレステロール類と して好ましくは、 コレス夕ノール、 コプロスタノール、 ァセチルコレス夕ノール、 ァセチルコプロスタノール、 コレスタノン、 コプロス夕ノン等が挙げられ、 さら に好ましくは、 コレスタノ一ル、 ァセチルコレス夕ノール、 コレスタノン等があ げられる。 Starting materials such as cholesterols having a hydrogen atom at the 25-position include cholesterol double bond-saturated compounds (for example, cholestanol ゃ coprostanol) and cholesterol double bonds that are oxidatively stable protecting groups. (For example, a bromine adduct of cholesterol), a compound in which the hydroxyl group at position 3 of these compounds is protected with a protecting group such as an acetyl group (eg, acetyl cholesterol, acetyl propyl prostanol), (Eg, cholestanone, coprostanone). Further, these compounds may have a substituent or a functional group (for example, an acetyl group or a halogen atom) which is stable to oxidation. Preferable examples of cholesterol include cholesterol, coprostanol, acetylcholethanol, acetylcoprostanol, cholestanone, coprosylnon, and the like. can give.
本発明の好ましい態様の一例は、 コレステロールを常法により 5位の二重結合 を飽和してコレスタノール誘導体へと変換した後、 必要に応じ水酸基の保護また は酸化を行い、 得られた化合物を、 ルテニウム化合物を触媒として過沃素酸等の 共酸化剤を用いる酸化系を用いて酸化する方法である。 これを式に示す。 An example of a preferred embodiment of the present invention is to convert a cholesterol to a cholestanol derivative by saturating the double bond at the 5-position by a conventional method, and then protecting or oxidizing a hydroxyl group as necessary. In this method, a ruthenium compound is used as a catalyst to perform oxidation using an oxidation system using a co-oxidant such as periodic acid. This is shown in the equation.
(式中、 R 2は同一でも異なっていてもよく、 水素原子、 保護されていても よい水酸基等を示すか、 または一緒になって = 0を示す。 ただし、 同時に水素原 子または同時に水酸基であることはない。 R t、 R 2のいずれかが水酸基である場 合には生成物の Ri、 R 2は一緒になって = 0となる。 ） ここで得られた生成物は 必要に応じ常法により還元、 脱保護、 二重結合の導入反応などを行うことにより コレステロールの 2 5位水酸化体が得られることとなる。 (In the formula, R 2 may be the same or different, and represents a hydrogen atom, an optionally protected hydroxyl group, or the like, or together represents 0. However, simultaneously, a hydrogen atom or a hydroxyl group represents If either R t or R 2 is a hydroxyl group, the product Ri and R 2 together = 0.) The product obtained here is optional. By performing reduction, deprotection, double bond introduction reaction, etc. by a conventional method, the 25-position hydroxylated form of cholesterol can be obtained.
ルテニウム化合物とは、 ルテニウムの塩類またはルテニウムの酸化物などを意 味し、 好ましくは三塩化ルテニウム、 二酸化ルテニウムまたは四酸化ルテニウム 等の化合物を意味する。 反応に用いられる触媒の量は原料化合物や反応条件など により異なるが好ましくは 1モル％から 5 0モル％、 さらに好ましくは 1モル％ から 1 0モル％の触媒が用いられる。 The ruthenium compound means a ruthenium salt or ruthenium oxide, preferably a compound such as ruthenium trichloride, ruthenium dioxide or ruthenium tetroxide. The amount of the catalyst used in the reaction varies depending on the starting compounds, reaction conditions, and the like, but is preferably 1 mol% to 50 mol%, more preferably 1 mol% to 10 mol%.
共酸化剤としては、 過沃素酸塩類、 次亜塩素酸塩類等の無機酸化剤やモルホリ ンォキシド等の有機酸化剤を意味し、 これらの酸化剤は安価で安定であり、 ルテ 二ゥム化合物の触媒とともに酸化反応系を形成するものである。 The co-oxidizing agent means an inorganic oxidizing agent such as periodates and hypochlorites, and an organic oxidizing agent such as morpholinoxide. These oxidizing agents are inexpensive and stable. It forms an oxidation reaction system with the catalyst.
本反応に使用する溶媒としては、 水、 およびへキサン、 ブタノン、 酢酸ェチル、 四塩化炭素またはジクロロメタン等の酸化条件下に安定な飽和炭化水素類、 ケト ン類、 エステル類、 ハロゲン化炭化水素類またはそれらの混合物を、 その他ァセ トニトリル等の溶媒の存在下または非存在下で、 二相の溶媒系で実施されるのが 望ましい。 Solvents used in this reaction include water and saturated hydrocarbons, ketones, esters, halogenated hydrocarbons that are stable under oxidizing conditions such as hexane, butanone, ethyl acetate, carbon tetrachloride or dichloromethane. Alternatively, the mixture is desirably carried out in a two-phase solvent system in the presence or absence of a solvent such as acetonitrile.
本反応は 1 0 °Cから 8 0 °C、 好ましくは 2 0 °Cから 5 0 °Cで行われる。 This reaction is carried out at 10 ° C to 80 ° C, preferably at 20 ° C to 50 ° C.
本反応の反応時間は、 反応液を薄層クロマトグラフィー、 高速液体クロマトグ ラフィ一等で反応を追跡し、 その進行具台により選択できる。 The reaction time of this reaction can be selected according to the progress of the reaction by tracking the reaction with thin layer chromatography, high performance liquid chromatography, or the like.
目的物の 2 5位水酸化体は、 反応液そのものから、 または新たに適切な溶媒を 加え、 溶媒抽出により目的物を有機層により集めた後、 通常の手段で単離精製で
S o。 The 25-hydroxylated product of the target compound can be isolated and purified by ordinary means after collecting the target product in the organic layer by solvent extraction from the reaction solution itself or by adding a new appropriate solvent. S o.
実施例 Example
以下に実施例を挙げて本発明をさらに詳細に説明するが、 本発明の範囲はこれ らの実施例によって制限的に解釈されるべきものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention should not be construed as being limited by these Examples.
(実施例 1) 25—ヒ ドロキシー 5 ーコレスタン一 3—オンの合成 Example 1 Synthesis of 25-hydroxy-5-cholestan-3-one
ジクロルメタン 25m 1、 ァセトニトリル 1 Om 1および水 3 Om 1の混合溶 媒に、 コレスタノール 3. 89 gを溶解した。 これに過沃素酸ナトリウム 9. 6 3 g、 三塩化ルテニウム水和物 0. 131 gを加え、 室温で 62時間撹拌した。 反応液に、 撹拌下、 充分量のヒ ドロ亜硫酸ナトリウム （ソジゥムハイ ドロサル フアイ ト） の粉末を加え、 過剰の酸化剤を分解した。 不溶物を濾別後、 ジクロル メタン溶液部を乾燥後濃縮した。 これを酢酸ェチルーへキサンを溶出溶媒とする シリカゲルカラムクロマトグラフィーに付し、 目的物を分取した。 収量 1. 19 g、 収率 29% 3.89 g of cholestanol was dissolved in a mixed solvent of 25 ml of dichloromethane, 1 Om1 of acetonitrile and 3 Om1 of water. To this, 9.63 g of sodium periodate and 0.131 g of ruthenium trichloride hydrate were added, and the mixture was stirred at room temperature for 62 hours. To the reaction solution, a sufficient amount of sodium hydrosulfite (sodium hydrosulfite) powder was added with stirring to decompose excess oxidizing agent. After filtering off the insolubles, the dichloromethane solution was dried and concentrated. This was subjected to silica gel column chromatography using ethyl acetate-hexane as an eluting solvent to obtain the desired product. Yield 1.19 g, 29% yield
融点および1 H NMRは、 文献 （J. Or g. Chem. 1992, 57， 5 052) の値に一致した。 Melting points and 1 H NMR were in accordance with literature values (J. Org. Chem. 1992, 57, 5052).
(実施例 2) 25—ヒドロキシー 5 α—コレスタン一 3—オンの合成 Example 2 Synthesis of 25-hydroxy-5α-cholestan-3-one
実施例 1におけるコレスタノ一ルの代わりに、 5α—コレスタン一 3—オン 3. 87 gを使用して、 実施例 1と同様の反応、 操作を行った。 収量 1. 05 g、 収 率 26%。 The same reaction and operation as in Example 1 were performed using 3.87 g of 5α-cholestan-3-one in place of cholestanol in Example 1. Yield 1.05 g, 26% yield.
(実施例 3) 25—ヒ ドロキシーコレスタノールアセテートの合成 Example 3 Synthesis of 25-hydroxycholestanol acetate
ジクロルメタン 36 m 1、 ァセトニトリル 36 m 1および水 53 m 1の混合溶 媒に、 撹拌下コレスタノールアセテート 10. 77g、 過沃素酸ナトリウム 24. 06 gおよび三塩化ルテニウム水和物 0. 653 gを加えた。 反応液を 8時間 2 0分還流した。 反応液を冷却後、 撹拌下、 充分量のヒ ドロ亜硫酸ナトリウム （ソ ジゥムハイ ドロサルフアイ ト） の粉末を加え、 過剰の酸化剤を分解した。 不溶物 を濾別後、 ジクロルメタン溶液部を乾燥後濃縮した。 これを酢酸ェチルーへキサ ンを溶出溶媒とするシリカゲルカラムクロマトグラフィーに付し、 目的物を分取 した。 収量 2. 01 g、 収率 18% To a mixed solvent of 36 m 1 of dichloromethane, 36 m 1 of acetonitrile and 53 m 1 of water, 10.77 g of cholestanol acetate, 24.06 g of sodium periodate and 0.653 g of ruthenium trichloride hydrate were added with stirring. Was. The reaction was refluxed for 8 hours and 20 minutes. After cooling the reaction solution, a sufficient amount of sodium hydrosulfite (sodium hydrosulfite) powder was added with stirring to decompose excess oxidizing agent. After filtering off insolubles, the dichloromethane portion was dried and concentrated. This was subjected to silica gel column chromatography using ethyl acetate-hexane as an eluting solvent to obtain the desired product. Yield 2.01 g, Yield 18%
融点 123°C
lH NMR (270MHz、 CDC ") Melting point 123 ° C l H NMR (270MHz, CDC ")
δ ： 0. 65 (s, 3H)、 0. 82 (s, 3H) 、 0. 92 (d, J = 6. 3 Hz, 3H) . 1. 21 (s， 6H) 、 2. 02 (s， 3H) 、 4. 68 (m， 1H) 、 0. 7-2. 2 (m， 3 OH) δ: 0.65 (s, 3H), 0.82 (s, 3H), 0.92 (d, J = 6.3 Hz, 3H) .1.21 (s, 6H), 2.02 (s , 3H), 4.68 (m, 1H), 0.7-2.2 (m, 3 OH)
産業上の利用可能性 Industrial applicability
本発明の方法により、 コレステロール類の 25位水酸化体を安価かつ安全に大 量供給することが可能になった。 すなわち、 本発明は医薬品の製造中間体として 有用なコレステロール類の 25位水酸化体の工業的製造において、 ①出発原料の 安価かつ大量な確保、 ②製造工程の大幅な短縮、 ③毒性や危険性の高い薬品の使 用の回避、 ④無水条件の回避など操作性の向上、 ⑤工程短縮による製造設備の大 幅な削減、 ⑥必然的な製造コス卜の低減などを可能にするものである。
ADVANTAGE OF THE INVENTION By the method of this invention, it became possible to supply the 25-position hydroxylated product of cholesterol cheaply and safely in large quantities. In other words, the present invention relates to the industrial production of the 25-hydroxylated cholesterol, which is useful as an intermediate for the production of pharmaceuticals, by (1) securing inexpensive and large quantities of starting materials, (2) significantly reducing the production process, and (3) toxicity and danger. It is possible to avoid the use of highly expensive chemicals, 向上 improve operability such as avoiding anhydrous conditions, ⑤ drastically reduce manufacturing equipment by shortening the process, ⑥ reduce inevitable manufacturing costs.
Claims
1 . コレステロール類の 2 5位の水素原子を水酸基に変換する反応において、 ルテニウム化合物を触媒として用いることを特徴とする 2 5—ヒドロキシコレス テロール類の製造方法。 1. A method for producing 25-hydroxycholesterols, wherein a ruthenium compound is used as a catalyst in a reaction for converting a hydrogen atom at the 25-position of cholesterol to a hydroxyl group.
2. コレステロール類がコレスタノール、 ァセチルコレスタノールまたはコレ スタノンである請求の範囲第 1項に記載の製造方法。 2. The production method according to claim 1, wherein the cholesterol is cholestanol, acetylcholestanol or cholestanone.
3. ルテニウム化合物がルテニウムの塩類またはルテニウムの酸化物である請 求の範囲第 1項に記載の製造方法。 3. The method according to claim 1, wherein the ruthenium compound is a ruthenium salt or ruthenium oxide.
4. ルテニウム化合物が三塩化ルテニウム、 二酸化ルテニウムまたは四酸化ル テニゥムである請求の範囲第 3項に記載の製造方法。 4. The method according to claim 3, wherein the ruthenium compound is ruthenium trichloride, ruthenium dioxide or ruthenium tetroxide.
5. 触媒使用量が 1モル％から 5 0モル％である請求の範囲第 1項に記載の製 造方法。 5. The production method according to claim 1, wherein the amount of the catalyst used is 1 mol% to 50 mol%.
6. 触媒使用量が 1モル％から 1 0モル％である請求の範囲第 5項に記載の製 造方法。 6. The method according to claim 5, wherein the amount of the catalyst used is 1 mol% to 10 mol%.
7. 共酸化剤を用い 請求の範囲第 1項に記載の製造方法。 7. The production method according to claim 1, wherein a co-oxidant is used.
8. 共酸化剤が過沃素酸塩類、 次亜塩素酸塩類またはモルホリンォキシドであ る請求の範囲第 7項に記載の製造方法。 8. The production method according to claim 7, wherein the co-oxidizing agent is a periodate, a hypochlorite, or morpholine oxide.
9. 反応温度が 1 0 °Cから 8 0 °Cである請求の範囲第 1項に記載の製造方法。 9. The production method according to claim 1, wherein the reaction temperature is from 10 ° C to 80 ° C.
1 0. 反応温度が 2 0 °Cから 5 0 °Cである請求の範囲第 9項に記載の製造方法。
10. The production method according to claim 9, wherein the reaction temperature is from 20 ° C to 50 ° C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU10340/95A AU1034095A (en) | 1993-11-19 | 1994-11-17 | Process for producing 25-hydroxylated cholesterol |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5/338727 | 1993-11-19 | ||
| JP33872793 | 1993-11-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1995014032A1 true WO1995014032A1 (en) | 1995-05-26 |
Family
ID=18320901
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP1994/001937 WO1995014032A1 (en) | 1993-11-19 | 1994-11-17 | Process for producing 25-hydroxylated cholesterol |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU1034095A (en) |
| WO (1) | WO1995014032A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3920531A (en) * | 1973-04-01 | 1975-11-18 | Yehuda Mazur | Preparation of derivatives of cholesterol |
| JPS55108898A (en) * | 1979-02-15 | 1980-08-21 | Teijin Ltd | 25-hydroxy-24-oxocholesterol derivative and its preparation |
-
1994
- 1994-11-17 WO PCT/JP1994/001937 patent/WO1995014032A1/en active Application Filing
- 1994-11-17 AU AU10340/95A patent/AU1034095A/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3920531A (en) * | 1973-04-01 | 1975-11-18 | Yehuda Mazur | Preparation of derivatives of cholesterol |
| JPS55108898A (en) * | 1979-02-15 | 1980-08-21 | Teijin Ltd | 25-hydroxy-24-oxocholesterol derivative and its preparation |
Non-Patent Citations (1)
| Title |
|---|
| J. CHEM. SOC., PERKIN TRANS. 1, No. 23 (1977), pages 2565-2571. * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU1034095A (en) | 1995-06-06 |
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