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1. 发明授权

US06426420B1 Process for producing isocoumarines and intermediates for the same 失效
标题翻译：生产异香豆素及其中间体的方法
公开(公告)号：US06426420B1
公开(公告)日：2002-07-30
申请号：US09610362
申请日：2000-07-05
申请人： Toshio Tsuchida , Hazuki Nagai , Takashi Nakashima , Masashi Yoshida , Kaname Konuki , Asako Kuroda , Kunio Isshiki , Tomio Takeuchi
发明人： Toshio Tsuchida , Hazuki Nagai , Takashi Nakashima , Masashi Yoshida , Kaname Konuki , Asako Kuroda , Kunio Isshiki , Tomio Takeuchi
IPC分类号： C07D31176
CPC分类号： C07D311/76 , C07C67/31 , C07C67/343 , C07C67/46 , C07C69/92 , Y02P20/55 , C07C69/88
摘要： Provided is a process for producing an isocoumarin-3-yl-acetic acid derivative, characterized by reacting a homophthalic acid derivative represented by a formula: (wherein Rc, R2 and R are mainly protecting groups) with a malonic acid derivating represented by a formula: (wherein R is an organic group including a lower alkyl group; R3 is a protecting group for a carboxyl group; and X is a halogen atom or a —OM group (wherein M is alkaline metal or alkaline earth metal)). According to the above process, various isocoumarin-3-yl-acetic acid derivatives can efficiently be provided.
摘要翻译：提供了一种制备异香豆素-3-基 - 乙酸衍生物的方法，其特征在于使由式（其中Rc，R2和R主要是保护基团）表示的均苯二甲酸衍生物与由式（其中，R为低级烷基的有机基团，R3为羧基的保护基，X为卤原子或-OM基）（其中，M为碱金属或碱土金属）。根据上述方法，可以有效地提供各种异香豆素-3-基 - 乙酸衍生物。

2. 发明授权

US06548695B2 Process for producing isocoumarins and intermediates for the same 失效
标题翻译：生产异香豆素及其中间体的方法
公开(公告)号：US06548695B2
公开(公告)日：2003-04-15
申请号：US10119734
申请日：2002-04-11
申请人： Toshio Tsuchida , Hazuki Nagai , Takashi Nakashima , Masashi Yoshida , Kaname Konuki , Asako Kuroda , Kunio Isshiki , Tomio Takeuchi
发明人： Toshio Tsuchida , Hazuki Nagai , Takashi Nakashima , Masashi Yoshida , Kaname Konuki , Asako Kuroda , Kunio Isshiki , Tomio Takeuchi
IPC分类号： C07C51493
CPC分类号： C07D311/76 , C07C67/31 , C07C67/343 , C07C67/46 , C07C69/92 , Y02P20/55 , C07C69/88
摘要： Provided is a process for producing an isocoumarin-3-yl-acetic acid derivative, characterized by reacting a homophthalic acid derivative represented by a formula: (wherein Rc, R2 and R are mainly protecting groups) with a malonic acid derivating represented by a formula: (wherein R is an organic group including a lower alkyl group; R3 is a protecting group for a carboxyl group; and X is a halogen atom or a —OM group (wherein M is alkaline metal or alkaline earth metal)). According to the above process, various isocoumarin-3-yl-acetic acid derivatives can efficiently be provided.
摘要翻译：提供了一种制备异香豆素-3-基 - 乙酸衍生物的方法，其特征在于使由式（其中Rc，R2和R主要是保护基团）表示的均苯二甲酸衍生物与由式（其中，R为低级烷基的有机基团，R3为羧基的保护基，X为卤原子或-OM基）（其中，M为碱金属或碱土金属）。根据上述方法，可以有效地提供各种异香豆素-3-基 - 乙酸衍生物。

3. 发明申请

US20110319644A1 PROCESS FOR PRODUCTION OF 1-HYDROXY-19-NORCYCLOVITAMIN D DERIVATIVE AND INTERMEDIATE FOR THE PRODUCTION 审中-公开
标题翻译：生产1-羟基-19-硝基维生素D衍生物和生产中间体的方法
公开(公告)号：US20110319644A1
公开(公告)日：2011-12-29
申请号：US12312209
申请日：2007-11-01
申请人： Asako Toyoda , Hazuki Nagai , Kaname Konuki , Toshio Tsuchida
发明人： Asako Toyoda , Hazuki Nagai , Kaname Konuki , Toshio Tsuchida
IPC分类号： C07C401/00
CPC分类号： C07C401/00
摘要： A cyclovitamin D derivative produced from 25-hydroxyvitamin D is reacted with osmium tetraoxide or a permanganic acid salt to produce a 10,19-diolcyclovitamin D derivative. The 10,19-diolcyclovitamin D derivative is reacted with a perhalogenic acid salt or lead tetraacetate to produce a 10-oxocyclovitamin D derivative. A 1-hydroxycyclovitamin D derivative is produced from the 10-oxocyclovitamin D derivative via a cyclovitamin D derivative and a 1,10-olefincyclovitamin D derivative. The 1-hydrocyclovitamin D derivative is subjected to solvolysis, thereby producing a 1-hydroxy-19-norviatmin D derivative. Thus provided are a novel process for production of 1-hydroxy-19-norcyclovitamin D derivative that is utilizable as an intermediate in the synthesis of 1-hydroxy-19-norvitamin D derivative which is useful as a pharmaceutical agent; and an intermediate for the production.
摘要翻译：由25-羟基维生素D产生的环维生素D衍生物与四氧化锇或高锰酸盐反应，生成10,19-二醇环化维生素D衍生物。使10,19-二醇类环维生素D衍生物与全卤酸盐或四乙酸铅反应生成10-氧代环维生素D衍生物。通过环维生素D衍生物和1,10-烯柔性维生素D衍生物从10-氧代环维生素D衍生物产生1-羟基环维生素D衍生物。 1-环氢维生素D衍生物进行溶剂解，由此生成1-羟基-19-诺维那敏D衍生物。因此提供了可用作合成作为药剂的1-羟基-19-去甲维生素D衍生物的合成中间体的1-羟基-19-去甲柔比星D衍生物的新方法。和生产中间体。

4. 发明申请

US20080050787A1 Method for Manufacturing Optically Active Tetrahydrothiophene Derivative and Method for Crystallization of Optically Active Tetrahydrothiophene-3-Ol 审中-公开
标题翻译：光学活性四氢噻吩衍生物的制备方法和光活性四氢噻吩-3-O的结晶方法
公开(公告)号：US20080050787A1
公开(公告)日：2008-02-28
申请号：US10581366
申请日：2004-12-01
申请人： Hazuki Nagai , Kaname Konuki , Masashi Ito , Tomohiro Sameshima
发明人： Hazuki Nagai , Kaname Konuki , Masashi Ito , Tomohiro Sameshima
IPC分类号： C12P17/00 , C07D333/32
CPC分类号： C12P17/167
摘要： A method for manufacturing (R)-tetrahydrothiophene-3-ol denoted by formula (II): by bioconversion of tetrahydrothiophene-3-one denoted by formula (I): to (R)-tetrahydrothiophene-3-ol denoted by formula (II). It comprises the steps of: (A) incubating the tetrahydrothiophene-3-one denoted by formula (I) in the presence of a strain, or a preparation of a cultured cell thereof, belonging to Penicillium, Aspergillus, or Streptomyces that is capable of said bioconversion; and (B) collecting the (R)-tetrahydrothiophene-3-ol denoted by formula (II) from incubated solution. A method for crystallization of optically active tetrahydrothiophene-3-ol of improved optical purity, characterized by maintaining a solution comprising optically active tetrahydrothiophene-3-ol and organic solvent at equal to or lower than 1° C. to cause optically active tetrahydrothiophene-3-ol to crystallize from said solution, or characterized by adding optically active tetrahydrothiophene-3-ol dropwise to organic solvent at a solution temperature of equal to or lower than 1° C. to cause optically active tetrahydro thiophene-3-ol to crystallize.
摘要翻译：由式（II）表示的（R） - 四氢噻吩-3-醇的制造方法：通过式（I）表示的四氢噻吩-3-酮的生物转化：式（II）表示的（R） - 四氢噻吩-3-醇）。其包括以下步骤：（A）在菌株存在下将式（I）表示的四氢噻吩-3-酮或其培养细胞的制剂，属于青霉属，曲霉属或链霉菌属，其能够说生物转化和（B）从温育溶液中收集由式（II）表示的（R） - 四氢噻吩-3-醇。一种提高光学纯度的光学活性四氢噻吩-3-醇的结晶方法，其特征在于将含有光学活性四氢噻吩-3-醇和有机溶剂的溶液保持在等于或低于1℃，使光学活性的四氢噻吩-3 - 醇从所述溶液中结晶，或者特征在于在等于或低于1℃的溶液温度下将光学活性的四氢噻吩-3-醇滴加到有机溶剂中，使光学活性的四氢噻吩-3-醇结晶。

5. 发明申请

US20090177002A1 Method For Preparing Indene Derivatives, And Intermediates For Preparation Of Derivatives 审中-公开
标题翻译：制备茚衍生物的方法及制备衍生物的中间体
公开(公告)号：US20090177002A1
公开(公告)日：2009-07-09
申请号：US12225123
申请日：2007-03-14
申请人： Asako Toyoda , Hazuki Nagai
发明人： Asako Toyoda , Hazuki Nagai
IPC分类号： C07C45/27 , C07C401/00
CPC分类号： C07C45/58 , C07B53/00 , C07C41/48 , C07C45/28 , C07C45/298 , C07C45/30 , C07C49/743 , C07C49/755 , C07C67/29 , C07C67/293 , C07C401/00 , C07C2601/14 , C07C2602/24 , C07D301/14 , C07D303/14 , C07F7/1804 , C07F7/1892 , C07C69/007 , C07C69/145 , C07C43/30
摘要： Indene derivatives that are utilizable as intermediates in the synthesis of the vitamin D2 derivative paricalcitol, which is useful as pharmaceutical are efficiently prepared by subjecting a vitamin D2 derivative such as 25-hydroxyvitamin D2 to a two-steps oxidation reaction using an oxidizing agent such as potassium permanganates and sodium periodate in a suitable solvent such as methanol and ethanol.
摘要翻译：可用作合成维生素D2衍生物帕立骨糖醇的中间体的可以作为中间体的可用作药物的衍生物通过使用诸如25-羟基维生素D2的维生素D 2衍生物进行两步氧化反应而有效地制备，所述氧化反应使用氧化剂如高锰酸钾和高碘酸钠在合适的溶剂如甲醇和乙醇中。

6. 发明申请

US20110112298A1 METHOD FOR PRODUCING CAMPTOTHECIN DERIVATIVES 有权
标题翻译：生产角质层衍生物的方法
公开(公告)号：US20110112298A1
公开(公告)日：2011-05-12
申请号：US12994950
申请日：2009-05-22
申请人： Asako Toyoda , Hazuki Nagai , George Wanyoike
发明人： Asako Toyoda , Hazuki Nagai , George Wanyoike
IPC分类号： C07D471/14
CPC分类号： C07D491/22 , B01J23/755 , B01J25/02
摘要： The invention offers a method of hydrogenating camptothecin in inert solvent in the presence of nickel catalyst, whereby selective hydrogenation of camptothecin can be very efficiently accomplished using the low-cost catalyst.
摘要翻译：本发明提供了一种在镍催化剂存在下在惰性溶剂中氢化喜树碱的方法，由此可以使用低成本催化剂非常有效地实现喜树碱的选择性氢化。

7. 发明授权

US08299251B2 Method for producing camptothecin derivatives 有权
标题翻译：喜树碱衍生物的制备方法
公开(公告)号：US08299251B2
公开(公告)日：2012-10-30
申请号：US12994950
申请日：2009-05-22
申请人： Asako Toyoda , Hazuki Nagai , George Ng'ang'a Wanyoike
发明人： Asako Toyoda , Hazuki Nagai , George Ng'ang'a Wanyoike
IPC分类号： C07D491/22
CPC分类号： C07D491/22 , B01J23/755 , B01J25/02
摘要： The invention offers a method of hydrogenating camptothecin in inert solvent in the presence of nickel catalyst, whereby selective hydrogenation of camptothecin can be very efficiently accomplished using the low-cost catalyst.
摘要翻译：本发明提供了一种在镍催化剂存在下在惰性溶剂中氢化喜树碱的方法，由此可以使用低成本催化剂非常有效地实现喜树碱的选择性加氢。

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