公开(公告)号：US06500946B1

公开(公告)日：2002-12-31

申请号：US09567980

申请日：2000-05-10

申请人： Satoshi Takamatsu ,  Satoshi Katayama ,  Naoko Hirose ,  Kunisuke Izawa ,  Tokumi Maruyama

发明人： Satoshi Takamatsu ,  Satoshi Katayama ,  Naoko Hirose ,  Kunisuke Izawa ,  Tokumi Maruyama

IPC分类号： C07H1919

CPC分类号： C07D473/00 ,  C07H19/16

摘要： Novel intermediates of nucleoside derivatives, of which the 6-position of the nucleic acid base moiety is substituted with a halogen atom, are produced. Using those novel intermediates, even substrates, of which the 3′-position of the saccharide moiety is deoxylated, can be substituted at the 2′-position at an extremely high yield. Specifically, by subjecting a 3′-deoxy derivative of inosine to 6-halogenation to give a 6-halide of the derivative, and then subjecting it to 2′-deoxylation/substitution with a fluorine atom or the like, followed by further subjecting it to substitution with an amino group, a hydroxyl group or any other intended substituent at the 6-positioned halogen atom, nucleoside derivatives are produced at a high yield. Methods for producing nucleoside derivatives including 9-(2,3-dideoxy-2-fluoro-&bgr;-D-threo-pentofuranosyl)adenine (FddA) and their related compounds, in a simplified manner, at a high yield and at low costs, and especially Economical methods for substituting substrates, of which the 3′-position of the saccharide moiety is deoxylated, at the 2′-position to produce those nucleoside derivatives on an industrial scale are also provided.

摘要翻译： 产生其核酸碱基部分的6位被卤素原子取代的核苷衍生物的新型中间体。 使用这些新型中间体，其中糖基部分的3'-位脱氧的偶联底物可以在2'-位以非常高的收率被取代。 具体来说，通过使肌苷的3'-脱氧衍生物进行6-卤化，得到该衍生物的6-卤化物，然后用氟原子等进行2'-脱氧/取代，然后进一步对其进行 以6-取代的卤素原子被氨基，羟基或任何其它目的取代基取代，以高产率生产核苷衍生物。 以简单的方式以高产率和低成本制备包括9-（2,3-二脱氧-2-氟-β-D-苏 - 呋喃鸟糖基）腺嘌呤（FddA）及其相关化合物的核苷衍生物的方法， 并且还提供了用于将2'-位上的糖部分的3'-位脱氧的底物替代为工业规模生产这些核苷衍生物的经济方法。

公开(公告)号：US06579976B2

公开(公告)日：2003-06-17

申请号：US09427082

申请日：1999-10-26

申请人： Satoshi Takamatsu ,  Satoshi Katayama ,  Naoko Hirose ,  Kunisuke Izawa

发明人： Satoshi Takamatsu ,  Satoshi Katayama ,  Naoko Hirose ,  Kunisuke Izawa

IPC分类号： C07H19173

CPC分类号： C07H19/04

摘要： There can be provided an excellent industrial process for producing compounds having sugar-moiety hydroxyl groups or halogen atoms reduced in nucleic acids or in derivatives thereof by allowing O-thiocarbonyl derivatives of sugar-moiety hydroxyl groups or allowing halogenated derivatives in the sugar-moiety, in the nucleic acids or in derivatives thereof to react with any one of hypophosphorous acids (including salts thereof) and phosphites (esters) which are inexpensive, non-toxic and safely usable as radical reducing agents in industrial scale, in the presence of a radical reaction initiator. The process of the present invention is an industrially useful and highly safe process for reducing sugar-moiety hydroxyl groups and halogen atoms in nucleic acids or derivatives thereof (including nucleic acid-related compounds) at low costs.

摘要翻译： 可以提供通过使糖部分羟基的O-硫代羰基衍生物或糖部分中的卤代衍生物在核酸或其衍生物中还原的具有糖部分羟基或卤素原子的化合物的优异工业方法， 在核酸或其衍生物中，在碱性存在下，与工业规模的廉价，无毒和可安全地用作自由基还原剂的次磷酸（包括其盐）和亚磷酸酯（酯）中的任何一种反应， 反应引发剂。本发明的方法是以低成本还原核酸或其衍生物（包括核酸相关化合物）中的糖部分羟基和卤素原子的工业上有用和高度安全的方法。

公开(公告)号：US20050032889A1

公开(公告)日：2005-02-10

申请号：US10876844

申请日：2004-06-28

申请人： Shinji Kuroda ,  Tomoyuki Onishi ,  Naoko Hirose ,  Takayuki Hamada

发明人： Shinji Kuroda ,  Tomoyuki Onishi ,  Naoko Hirose ,  Takayuki Hamada

IPC分类号： C07C303/40 ,  C07C303/44 ,  C07C311/18 ,  C07C311/41 ,  A61K31/325

CPC分类号： C07C303/40 ,  C07B2200/07 ,  C07B2200/13 ,  C07C303/44 ,  C07C311/18 ,  C07C311/41

摘要： The present invention relates to a method of producing a highly pure crystal, which includes crystallization of a benzenesulfonamide derivative of the following formula (1) using a polar solvent as a good solvent (e.g., alcohol or a mixed solvent of alcohol and water) and water as a poor solvent, and a novel crystal of a nitrobenzenesulfonamide derivative of the following formula (2), which is an intermediate for the derivative, and a production method thereof:

摘要翻译： 本发明涉及高纯度晶体的制造方法，该方法包括使用极性溶剂作为良溶剂（例如醇或醇和水的混合溶剂）和下述式（1）的苯磺酰胺衍生物的结晶和 水作为不良溶剂，以及作为衍生物的中间体的下述式（2）的硝基苯磺酰胺衍生物的新结晶及其制造方法：

公开(公告)号：US20070129443A1

公开(公告)日：2007-06-07

申请号：US11582504

申请日：2006-10-18

申请人： Yasuyuki Otake ,  Naoko Hirose ,  Masanobu Yatagai

发明人： Yasuyuki Otake ,  Naoko Hirose ,  Masanobu Yatagai

IPC分类号： A61K31/137 ,  C07C209/06

CPC分类号： C07C269/04 ,  C07B2200/07 ,  C07C215/28 ,  C07D301/26 ,  C07D303/36 ,  C07C271/16

摘要： Highly pure (2R,3S)-3-tert-butoxycarbonylamino-1-chloro-2-hydroxy-4-phenylbutane or (2S,3R)-3-tert-butoxycarbonylamino-1-chloro-2-hydroxy-4-phenylbutane may be conveniently produced in high yield by: (a) reacting compound (1) with lithiumchloromethane to give compound (2) and at least a byproduct; (b) dissolving compound (2) and the byproduct in a polar solvent and adding water to the solution to precipitate compound (2) as crystals; (c) reducing the crystals of compound (2) to give compound (3) and at least its diastereomer as an impurity; (d) adding sulfuric acid thereto to give compound (4) and at least its diastereomer as an impurity; and (e) precipitating compound (4) as crystals from a solution containing acetic acid ester or acetic acid ester.

摘要翻译： 高纯度（2R，3S）-3-叔丁氧基羰基氨基-1-氯-2-羟基-4-苯基丁烷或（2S，3R）-3-叔丁氧基羰基氨基-1-氯-2-羟基-4-苯基丁烷可以 通过以下方法可以方便地以高产率制备：（a）使化合物（1）与氯化锂反应得到化合物（2）和至少一种副产物; （b）将化合物（2）和副产物溶解在极性溶剂中，并向溶液中加入水以使化合物（2）晶体沉淀; （c）减少化合物（2）的晶体，得到化合物（3）和至少其作为杂质的非对映异构体; （d）向其中加入硫酸，得到化合物（4）和至少其作为杂质的非对映异构体; 和（e）从含有乙酸酯或乙酸酯的溶液中沉淀出结晶的化合物（4）。