JPH069645A - Production of ucn-01 - Google Patents
Production of ucn-01Info
- Publication number
- JPH069645A JPH069645A JP4162813A JP16281392A JPH069645A JP H069645 A JPH069645 A JP H069645A JP 4162813 A JP4162813 A JP 4162813A JP 16281392 A JP16281392 A JP 16281392A JP H069645 A JPH069645 A JP H069645A
- Authority
- JP
- Japan
- Prior art keywords
- ucn
- aqueous solution
- staurosporine
- alkali
- dimethyl sulfoxide
- 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
Landscapes
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は抗腫瘍作用および抗菌作
用を有するＵＣＮ−０１の製造法に関する。TECHNICAL FIELD The present invention relates to a method for producing UCN-01 having antitumor activity and antibacterial activity.
【０００２】[0002]
【従来の技術】ＵＣＮ−０１の製造法としてこれまで以
下に示す２方法が知られている。 （１）ストレプトマイセス属に属し、ＵＣＮ−０１を生
産する能力を有する微生物を培地に培養し、ＵＣＮ−０
１を採取する発酵法（特開昭６２−２２０１９６）。 （２）スタウロスポリンより容易に導かれる化合物
（Ａ）を酢酸中、四酢酸鉛を用いて酸化し、ついで接触
還元により脱保護を行いＵＣＮ−０１を得る化学合成法
（ＷＯ８９／０７１０５）。2. Description of the Related Art The following two methods are known so far as a method for producing UCN-01. (1) A microorganism belonging to the genus Streptomyces and having an ability to produce UCN-01 is cultured in a medium to give UCN-0.
Fermentation method for collecting 1 (JP-A-62-220196). (2) A chemical synthesis method (WO89 / 07105) in which the compound (A) which is easily derived from staurosporine is oxidized with lead tetraacetate in acetic acid and then deprotected by catalytic reduction to obtain UCN-01 (WO89 / 07105).
【０００３】[0003]
【化３】 [Chemical 3]
【０００４】しかしながら前者の発酵法では培養力価が
低く、また後者の化学合成法においてはスタウロスポリ
ンからＵＣＮ−０１を得るために３ステップを要するた
め化学収率が低い。However, in the former fermentation method, the culture titer is low, and in the latter chemical synthesis method, three steps are required to obtain UCN-01 from staurosporine, so the chemical yield is low.
【０００５】[0005]
【発明が解決しようとする課題】本発明の目的は、ＵＣ
Ｎ−０１を効率的かつ簡便に製造できる有利な方法を提
供することにある。SUMMARY OF THE INVENTION It is an object of the present invention to provide UC
An object of the present invention is to provide an advantageous method capable of efficiently and conveniently producing N-01.
【０００６】[0006]
【課題を解決するための手段】本発明は、式（Ｉ）The present invention provides a compound of formula (I)
【０００７】[0007]
【化４】 [Chemical 4]
【０００８】で表されるスタウロスポリンをジメチルス
ルホキシド（以下、ＤＭＳＯと略す）およびアルカリ水
溶液からなる溶液中で酸化することを特徴とする式（I
I）The staurosporine represented by the formula (I) is characterized in that it is oxidized in a solution consisting of dimethyl sulfoxide (hereinafter abbreviated as DMSO) and an aqueous alkali solution.
I)
【０００９】[0009]
【化５】 [Chemical 5]
【００１０】で表されるＵＣＮ−０１の製造法に関す
る。アルカリ水溶液のアルカリ種としてはナトリウム、
カリウムのようなアルカリ金属の水酸化物、カルシウ
ム、マグネシウムのようなアルカリ土類金属の水酸化物
等が用いられ、なかでも水酸化ナトリウム、水酸化カリ
ウムが好ましい。その濃度としては、０.１Ｎ〜１０Ｎ
の水溶液を用いることが好ましい。The present invention relates to a method for producing UCN-01 represented by Sodium as the alkaline species of the alkaline aqueous solution,
Alkali metal hydroxides such as potassium and alkaline earth metal hydroxides such as calcium and magnesium are used. Of these, sodium hydroxide and potassium hydroxide are preferable. Its concentration is 0.1N-10N
It is preferable to use an aqueous solution of
【００１１】ＤＭＳＯとアルカリ水溶液の混合比率は２
／１〜１０／１が好適であり、スタウロスポリン１ｇ当
たり、該混合溶媒５〜１００mlを用いればよい。反応温
度は通常０〜５０℃で、反応時間は１〜２４時間の範囲
で行われる。反応終了後、例えば反応混合物を有機溶媒
により抽出しその有機層をクロマトグラフィー等の精製
操作に付すことによってＵＣＮ−０１を分離取得するこ
とができる。The mixing ratio of DMSO and alkaline aqueous solution is 2
/ 1 to 10/1 is preferable, and 5 to 100 ml of the mixed solvent may be used per 1 g of staurosporine. The reaction temperature is usually 0 to 50 ° C., and the reaction time is 1 to 24 hr. After the completion of the reaction, for example, UCN-01 can be separated and obtained by extracting the reaction mixture with an organic solvent and subjecting the organic layer to a purification operation such as chromatography.
【００１２】以下、実施例により本発明を説明する。The present invention will be described below with reference to examples.
【００１３】[0013]
実施例１ スタウロスポリン１００mg（０.２１mmol）をＤＭＳＯ
４ml、２Ｎ水酸化ナトリウム水溶液１mlに溶解し室温で
一晩攪拌した。反応溶液を酢酸エチルで希釈し、水、飽
和食塩水で順次洗浄後無水硫酸マグネシウムで乾燥し
た。得られた溶液の溶媒を留去し、残渣をシリカゲルカ
ラムクロマトグラフィー（クロロホルム、４％、６％、
１０％アセトン／クロロホルムで順次溶出）で精製しＵ
ＣＮ−０１、６０mg（収率５９％）を得た。Example 1 100 mg (0.21 mmol) of staurosporine in DMSO
It was dissolved in 4 ml of 2N aqueous sodium hydroxide solution and stirred at room temperature overnight. The reaction solution was diluted with ethyl acetate, washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent of the obtained solution was distilled off, and the residue was subjected to silica gel column chromatography (chloroform, 4%, 6%,
Purify with 10% acetone / chloroform)
60 mg (yield 59%) of CN-01 was obtained.
【００１４】実施例２ 実施例１において２Ｎ水酸化ナトリウム水溶液の代わり
に０.５Ｎ水酸化ナトリウム水溶液を用いる以外は実施
例１に準じた反応および分離精製を行い、スタウロスポ
リン３.０ｇよりＵＣＮ−０１、２.２ｇ（収率７０％）
を得た。Example 2 The reaction and separation and purification were carried out in the same manner as in Example 1 except that a 0.5N sodium hydroxide aqueous solution was used instead of the 2N sodium hydroxide aqueous solution, and UCN was extracted from 3.0 g of staurosporine. -01, 2.2 g (yield 70%)
Got
【００１５】[0015]
【発明の効果】本発明によれば、ＵＣＮ−０１を効率的
かつ簡便に製造することができる。According to the present invention, UCN-01 can be produced efficiently and easily.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｃ０７Ｄ 273:00 309:00） (72)発明者 斉藤 博満 静岡県三島市徳倉５−15−23─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification number Reference number within the agency FI technical display area C07D 273: 00 309: 00) (72) Inventor Hiromitsu Saito 5-15-23 Tokukura, Mishima City, Shizuoka Prefecture
Claims (1)
よびアルカリ水溶液からなる溶液中で酸化することを特
徴とする式（II） 【化２】 で表されるＵＣＮ−０１の製造法。1. Formula (I): The staurosporine represented by the formula (II) is characterized by being oxidized in a solution consisting of dimethyl sulfoxide and an alkaline aqueous solution. The manufacturing method of UCN-01 represented by.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04162813A JP3112343B2 (en) | 1992-06-22 | 1992-06-22 | Method for producing UCN-01 |
| US08/079,560 US5344926A (en) | 1992-06-22 | 1993-06-22 | Process for producing staurosporine derivatives |
| EP93109935A EP0575955B1 (en) | 1992-06-22 | 1993-06-22 | Process for producing staurosporine derivatives |
| ES93109935T ES2136103T3 (en) | 1992-06-22 | 1993-06-22 | PROCEDURE FOR THE PREPARATION OF STAUROSPORIN DERIVATIVES. |
| DE69326388T DE69326388T2 (en) | 1992-06-22 | 1993-06-22 | Process for the preparation of staurosporine derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04162813A JP3112343B2 (en) | 1992-06-22 | 1992-06-22 | Method for producing UCN-01 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH069645A true JPH069645A (en) | 1994-01-18 |
| JP3112343B2 JP3112343B2 (en) | 2000-11-27 |
Family
ID=15761715
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP04162813A Expired - Fee Related JP3112343B2 (en) | 1992-06-22 | 1992-06-22 | Method for producing UCN-01 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3112343B2 (en) |
-
1992
- 1992-06-22 JP JP04162813A patent/JP3112343B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP3112343B2 (en) | 2000-11-27 |
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