JP5376532B2 - カンプトテシン誘導体の製造方法 - Google Patents
カンプトテシン誘導体の製造方法 Download PDFInfo
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- JP5376532B2 JP5376532B2 JP2010514543A JP2010514543A JP5376532B2 JP 5376532 B2 JP5376532 B2 JP 5376532B2 JP 2010514543 A JP2010514543 A JP 2010514543A JP 2010514543 A JP2010514543 A JP 2010514543A JP 5376532 B2 JP5376532 B2 JP 5376532B2
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- JP
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- Prior art keywords
- nickel
- catalyst
- camptothecin
- reaction
- oxide
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
- B01J23/74—Iron group metals
- B01J23/755—Nickel
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J25/00—Catalysts of the Raney type
- B01J25/02—Raney nickel
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【非特許文献1】Sawada et al.,Chem.Pharm.Bull.39(12)3183−3188(1991)
【非特許文献2】Shaw et al.,J.Heterocyclic Chem.,24,1477−1483(1987)
【発明の概要】
【発明が解決しようとする課題】
カラム:カプセルパック C18 MGII(資生堂)(4.6mm I.D.×250mm,5μm)
移動相:A/B=1/1(A:酢酸ナトリウム緩衝液(pH4.04)、B:5mMヘプタスルホン酸ナトリウムメタノール溶液)
流速:1.0mL/分
カラム温度:40℃
検出:UV254nm
350mL高圧オートクレーブ中でカンプトテシン6g(17.2mmol)を酢酸60mLに懸濁し、安定化ニッケル触媒(N113)2.4gを加え、水素で置換し2.0MPaで110℃にて撹拌しながら3時間加熱したところ原料が消失した。反応液を室温にした後、セライト3g上でろ過し酢酸30mLにて洗浄した。このろ液をヘプタン(80mLx1回、60mLx2回)で洗浄した後、クロロホルム60mLを加え抽出し、有機層を水30mL、飽和食塩水30mLで順次洗浄した。有機層を硫酸マグネシウム2gで乾燥後ろ過濃縮した。得られた橙色オイルにクロロホルム10mLを加え35℃で加熱して均一溶液とし、ここへヘプタン10mLを添加したところ沈殿物が生成した。溶媒を減圧留去後、乾燥したところ橙色粉として1,2,6,7−テトラヒドロカンプトテシンを5.8g(収率:96.8%)得た(ジアステレオ異性体比*は21:76であった。)。
注)*: RRT0.62対RRT0.9の比を意味し、RRTに続く数値は、それぞれ、カンプトテシン(CPT)のリテンションタイムを1としたときの相対的なリテンションタイムを意味する。以下、同じ。
1H−NMR(500MHz,CDCl3)δ(ppm):7.04(1H,t),6.99(1H,d),6.69(1H,t),6.61(1H,s),6.60(1H,d),5.57(1H,d),5.16(1H,d),4.89(1H,t),4.31(1H,d),4.21(1H,dd),4.08(1H,dd),3.63(1H,s),2.88(1H,dd),2.84(1H,m),2.45(1H,dd),1.79(2H,m),0.98(3H,t)
1H−NMR(500MHz,CDCl3)δ(ppm):7.07(1H,t),7.03(1H,d),6.72(1H,t),6.64(1H,d),6.60(1H,s),5.59(1H,d),5.13(1H,d),4.89(1H,t),4.36(1H,d),4.19(1H,dd),4.13(1H,dd),3.65(1H,s),2.88(1H,dd),2.83(1H,m),2.45(1H,dd),1.77(2H,m),0.94(3H,t)
1H−NMR(500MHz,CDCl3)δ(ppm):7.64(1H,s),7.43(1H,s),5.72(1H,d),5.27(1H,d),5.05(2H,s),3.64(1H,s),3.05(2H,t),2.90(2H,t),1.88(6H,m),1.01(3H,t)
350mL高圧オートクレーブ中でカンプトテシン6g(17.2mmol)を酢酸60mLに懸濁し、安定化ニッケル触媒(N113)1.2gを加え、水素で置換し2.0MPaで110℃にて撹拌しながら6時間加熱したところ原料が消失した。反応液を室温にした後、セライト0.5g上でろ過し酢酸10mLにて洗浄した。本溶液のHPLC分析より、該実施例は、1,2,6,7−テトラヒドロカンプトテシンを97%の収量で取得できることが確認された(ジアステレオ異性体比は23対74であった。)。
1,2,6,7−テトラヒドロカンプトテシンの製造
実施例2と同様な操作で反応温度、触媒量、反応圧等を変更したところ下表の結果が得られた。
N113;ニッケル27%、酸化ニッケル(II)33%、を混合し珪藻土30%に担持させた触媒(日揮化学株式会社)
SN250;ニッケルまたは酸化ニッケル(II)55%を珪藻土に担持させた触媒(堺化学工業株式会社)
高圧オートクレーブ中で7−エチル−カンプトテシン0.5g(0.13mmol)を酢酸0.5mLに懸濁し、ニッケル触媒N113 20mgを加え、水素で置換し2.0MPaで110℃にて攪拌しながら6時間加熱したところ原料が消失した。反応液を室温にした後、PTFEフィルター(アドバンテック東洋株式会社DISMIC 13JP020AN)にてろ過し酢酸0.5mLにて洗浄した。本溶液はHPLC分析より7−エチル−1,2,6,7−テトラヒドロカンプトテシンを96%の収率で取得できることが確認された。
1H−NMR(500MHz,DMSO−d6)δ(ppm):7.0−6.8(2H,m),6.6−6.5(2H,m),6.30(1H,s),5.21(1H,s),4.91(1H,m),4.06(1H,m),3.91(1H,m),3.17(1H,m),3.01(1H,m),1.90(3H,m),1.72(2H,m),1.02(3H,t),0.78(3H,t)
Claims (5)
- Rが水素原子である請求項1記載の製造方法。
- ニッケル触媒が、金属ニッケル、還元ニッケル、安定化ニッケル、ニッケル‐珪藻土、ラネー型ニッケル、修飾ラネー型ニッケル、ギ酸ニッケル、漆原ニッケル、ホウ化ニッケル、酸化ニッケル、ニッケル錯体、ニッケル‐銅‐珪藻土、ニッケル‐ジルコニア‐珪藻土、ニッケル‐アルミナ、ニッケル‐シリカ‐アルミナ、ニッケル‐コバルト、ニッケル‐銅‐コバルト、ニッケル‐鉄、ニッケル‐鉄‐コバルト、ニッケル‐鉄‐リン、酸化ニッケル‐シリカ、酸化ニッケル‐酸化マグネシウム‐アルミナ及び酸化ニッケル‐三酸化モリブデン‐アルミナからなる群より選ばれる1種または2種以上であることを特徴とする請求項1または2記載の製造方法。
- ニッケル触媒がラネー型ニッケル、修飾ラネー型ニッケル、安定化ニッケルであることを特徴とする請求項1または2記載の製造方法。
- ニッケル触媒が安定化ニッケルであることを特徴とする請求項1または2記載の製造方法。
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JP2010514543A JP5376532B2 (ja) | 2008-05-29 | 2009-05-22 | カンプトテシン誘導体の製造方法 |
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JP2008140942 | 2008-05-29 | ||
JP2010514543A JP5376532B2 (ja) | 2008-05-29 | 2009-05-22 | カンプトテシン誘導体の製造方法 |
PCT/JP2009/059825 WO2009145282A1 (ja) | 2008-05-29 | 2009-05-22 | カンプトテシン誘導体の製造方法 |
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JPWO2009145282A1 JPWO2009145282A1 (ja) | 2011-10-13 |
JP5376532B2 true JP5376532B2 (ja) | 2013-12-25 |
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JP2010514543A Expired - Fee Related JP5376532B2 (ja) | 2008-05-29 | 2009-05-22 | カンプトテシン誘導体の製造方法 |
Country Status (9)
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US (1) | US8299251B2 (ja) |
EP (1) | EP2280013B1 (ja) |
JP (1) | JP5376532B2 (ja) |
KR (1) | KR101600114B1 (ja) |
CN (1) | CN102046634B (ja) |
AU (1) | AU2009252303B2 (ja) |
CA (1) | CA2725560C (ja) |
ES (1) | ES2425621T3 (ja) |
WO (1) | WO2009145282A1 (ja) |
Families Citing this family (4)
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US8865095B2 (en) * | 2011-12-20 | 2014-10-21 | Solvay Sa | Process for producing sodium bicarbonate |
US8722886B1 (en) * | 2012-11-13 | 2014-05-13 | Bionumerik Pharmaceuticals, Inc. | Methods for the total chemical synthesis of enantiomerically-pure 7-(2′-trimethylsilyl)ethyl camptothecin |
CN104774209B (zh) | 2014-01-15 | 2018-06-19 | 上海海和药物研究开发有限公司 | 一种9-烯丙基喜树碱衍生物的合成方法 |
US10766782B2 (en) | 2015-09-23 | 2020-09-08 | Solvay Sa | Production of crystalline sodium bicarbonate |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US20070149783A1 (en) * | 2005-12-26 | 2007-06-28 | Palle Venkata Raghavendra A | Process for preparing topotecan |
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JPS595188A (ja) | 1982-06-30 | 1984-01-12 | Yakult Honsha Co Ltd | 10−ヒドロキシカンプトテシンの製造法 |
US5004758A (en) * | 1987-12-01 | 1991-04-02 | Smithkline Beecham Corporation | Water soluble camptothecin analogs useful for inhibiting the growth of animal tumor cells |
ES2137932T3 (es) | 1990-09-28 | 2000-01-01 | Smithkline Beecham Corp | Procedimiento para la preparacion de analogos de camptotecina solubles en agua, asi como los compuestos 10-hidroxi-11-alcoxi-6-camptotecina. |
DE10106969C1 (de) * | 2001-02-15 | 2002-10-02 | Boehringer Ingelheim Pharma | Verfahren zur Reinigung und zur Herstellung von 20(S)-Camptothecin |
CN100344633C (zh) | 2003-05-12 | 2007-10-24 | 台湾神隆股份有限公司 | 用于制备7-烷基-10-羟基-20(s)-喜树碱的方法 |
CN1781923A (zh) * | 2004-11-29 | 2006-06-07 | 中国科学院成都有机化学有限公司 | 一种制备9-硝基-20(s)-喜树碱的方法 |
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- 2009-05-22 WO PCT/JP2009/059825 patent/WO2009145282A1/ja active Application Filing
- 2009-05-22 JP JP2010514543A patent/JP5376532B2/ja not_active Expired - Fee Related
- 2009-05-22 ES ES09754790T patent/ES2425621T3/es active Active
- 2009-05-22 KR KR1020107027676A patent/KR101600114B1/ko active IP Right Grant
- 2009-05-22 CA CA2725560A patent/CA2725560C/en not_active Expired - Fee Related
- 2009-05-22 CN CN2009801192400A patent/CN102046634B/zh not_active Expired - Fee Related
- 2009-05-22 AU AU2009252303A patent/AU2009252303B2/en not_active Ceased
- 2009-05-22 US US12/994,950 patent/US8299251B2/en active Active
- 2009-05-22 EP EP09754790.5A patent/EP2280013B1/en not_active Not-in-force
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US20070149783A1 (en) * | 2005-12-26 | 2007-06-28 | Palle Venkata Raghavendra A | Process for preparing topotecan |
Non-Patent Citations (2)
Title |
---|
JPN7013003228; Tsutomu Sugasawa et al.: Chemical & Pharmaceutical Bulletin Vol.22, No.4, 1974, p.771-781 * |
JPN7013003229; Jeffery L., Wood et al.: Journal of Organic Chemistry Vol.60, No.17, 1995, p.5739-5740 * |
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Publication number | Publication date |
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CA2725560C (en) | 2015-10-06 |
JPWO2009145282A1 (ja) | 2011-10-13 |
CN102046634B (zh) | 2013-04-24 |
KR101600114B1 (ko) | 2016-03-04 |
ES2425621T3 (es) | 2013-10-16 |
AU2009252303B2 (en) | 2013-04-04 |
EP2280013A1 (en) | 2011-02-02 |
CA2725560A1 (en) | 2009-12-03 |
EP2280013B1 (en) | 2013-07-10 |
AU2009252303A1 (en) | 2009-12-03 |
WO2009145282A1 (ja) | 2009-12-03 |
CN102046634A (zh) | 2011-05-04 |
US20110112298A1 (en) | 2011-05-12 |
US8299251B2 (en) | 2012-10-30 |
KR20110010767A (ko) | 2011-02-07 |
EP2280013A4 (en) | 2012-05-30 |
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