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公开(公告)号：US07329518B2
公开(公告)日：2008-02-12
申请号：US10669503
申请日：2003-09-25
CPC分类号： C12N9/0004 , C12P17/12 , C12P17/18 , C12P41/002
摘要： The present invention relates to a method of producing an optically active pyridineethanol derivative. More particularly, it relates to a method of producing an optically active polycyclic pyridineethanol derivative by causing an enzyme or enzyme source to act on polycyclic acetylpyridine derivatives.The present invention also relates to a novel enzyme which can be used in the production method mentioned above, a DNA coding for said enzyme, a recombinant vector having said DNA, and a transformant having said recombinant vector.The invention further relates to a method of producing an optically active polycyclic pyridineethanol derivative by causing the above novel enzyme or the above transformant to act on optically inactive polycyclic pyridineethanol derivatives.
摘要翻译： 本发明涉及一种制备光学活性吡啶乙醇衍生物的方法。 更具体地说，本发明涉及通过使酶或酶源作用于多环乙酰基吡啶衍生物来制备光学活性多环吡啶乙醇衍生物的方法。 本发明还涉及可用于上述制备方法的新型酶，编码所述酶的DNA，具有所述DNA的重组载体和具有所述重组载体的转化体。 本发明还涉及通过使上述新型酶或上述转化体作用于光学无活性的多环吡啶乙醇衍生物来制备光学活性多环吡啶乙醇衍生物的方法。
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公开(公告)号：US07332312B2
公开(公告)日：2008-02-19
申请号：US10512908
申请日：2003-04-30
CPC分类号： C12N9/0006 , C12Y101/01184
摘要： The present invention provides a novel polypeptide forming (R)-2-chloro-1-(3′-chlorophenyl)ethanol, a polynucleotide coding for said polypeptide, and use of the same.The present invention relates to a polypeptide having the following physical and chemical properties (1) to (4): (1) activity: acting on 2-chloro-1-(3′-chlorophenyl)ethanone with NADPH or NADH as a coenzyme, to form (R)-2-chloro-1-(31-chlorophenyl)ethanol; (2) optimum pH for activity: 5.0 to 6.0; (3) optimum temperature for activity: 40° C. to 50° C.; (4) molecular weight: about 40,000 as determined by gel filtration analysis, about 30,000 as determined by SDS polyacrylamide gel electrophoresis analysis. The present invention also relates to a polypeptide comprising the amino acid sequence shown under SEQ ID NO:1 in the sequence listing, a polynucleotide coding for said polypeptide, and a transformant producing said polypeptide at high levels.
摘要翻译： 本发明提供形成（R）-2-氯-1-（3'-氯苯基）乙醇的新型多肽，编码所述多肽的多核苷酸及其用途。 本发明涉及具有以下物理和化学性质（1）至（4）的多肽：（1）活性：以NADPH或NADH作为辅酶作用于2-氯-1-（3'-氯苯基）乙酮， 形成（R）-2-氯-1-（31-氯苯基）乙醇; （2）活性最佳pH：5.0〜6.0; （3）最适温度为40℃〜50℃。 （4）分子量：约40,000，通过凝胶过滤分析测定，约30,000，通过SDS聚丙烯酰胺凝胶电泳分析测定。 本发明还涉及包含序列表中SEQ ID NO：1所示氨基酸序列的多肽，编码所述多肽的多核苷酸，以及以高水平产生所述多肽的转化体。
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![Process for preparing optically active 2-[6-(hydroxy-methyl)-1,3-dioxan-4-yl] acetic acid derivatives](/abs-image/US/2006/11/02/US20060246557A1/abs.jpg.150x150.jpg)
3.发明申请Process for preparing optically active 2-[6-(hydroxy-methyl)-1,3-dioxan-4-yl] acetic acid derivatives 审中-公开光学活性的2- [6-（羟基 - 甲基）-1,3-二恶烷-4-基]乙酸衍生物的制备方法公开(公告)号：US20060246557A1
公开(公告)日：2006-11-02
申请号：US11477322
申请日：2006-06-30
CPC分类号： C07D319/06 , C12P7/42 , C12P17/06
摘要： The present invention is to provide a production technology by which an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative, which are of value as pharmaceutical intermediates, can be produced from inexpensive and readily available starting materials without using any extraordinary equipment such as an ultra-low-temperature reactor. The present invention is a production process of an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative which comprises reacting an enolate, prepared by permitting a base or a 0-valent metal to act on an acetic acid ester derivative with (S)-β-hydroxy-γ-butyrolactone at a temperature not lower than −30° C. to give a dihydroxyoxohexanoic acid derivative, treating the same with an acylating agent in the presence of a base to produce a dihydroxyoxohexanoic acid monoacyl derivative, reducing this compound with a microorganism to produce a trihydroxyhexanoic acid monoacyl derivative, treating this compound with an acetal-forming reagent in the presence of an acid catalyst to produce an acyloxy-methyldioxanylacetic acid derivative, and finally, subjecting this compound to solvolysis in the presence of a base.
摘要翻译： 本发明提供一种生产技术，通过该技术，可以以廉价的方式生产价值为医药中间体的光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物 和容易获得的起始材料，而不使用任何非常设备，例如超低温反应器。 本发明是光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物的制备方法，该方法包括使通过使碱或0价金属 在不低于-30℃的温度下用（S）-β-羟基-γ-丁内酯在乙酸酯衍生物上作用，得到二羟基氧代己酸衍生物，在酰化剂存在下用酰化剂处理 制备二羟基氧基己酸单酰基衍生物，用微生物还原该化合物以产生三羟基己酸单酰基衍生物，在酸催化剂存在下用缩醛形成试剂处理该化合物以产生酰氧基 - 甲基二恶烷基乙酸衍生物，最后 使该化合物在碱的存在下溶剂解。
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公开(公告)号：US20060046289A1
公开(公告)日：2006-03-02
申请号：US10512908
申请日：2003-04-30
CPC分类号： C12N9/0006 , C12Y101/01184
摘要： The present invention provides a novel polypeptide forming (R)-2-chloro-1-(3′-chlorophenyl)ethanol, a polynucleotide coding for said polypeptide, and use of the same. The present invention relates to a polypeptide having the following physical and chemical properties (1) to (4): (1) activity: acting on 2-chloro-1-(3′-chlorophenyl)ethanone with NADPH or NADH as a coenzyme, to form (R)-2-chloro-1-(31-chlorophenyl)ethanol; (2) optimum pH for activity: 5.0 to 6.0; (3) optimum temperature for activity: 40° C. to 50° C.; (4) molecular weight: about 40,000 as determined by gel filtration analysis, about 30,000 as determined by SDS polyacrylamide gel electrophoresis analysis. The present invention also relates to a polypeptide comprising the amino acid sequence shown under SEQ ID NO:1 in the sequence listing, a polynucleotide coding for said polypeptide, and a transformant producing said polypeptide at high levels.
摘要翻译： 本发明提供形成（R）-2-氯-1-（3'-氯苯基）乙醇的新型多肽，编码所述多肽的多核苷酸及其用途。 本发明涉及具有以下物理和化学性质（1）至（4）的多肽：（1）活性：以NADPH或NADH作为辅酶作用于2-氯-1-（3'-氯苯基）乙酮， 形成（R）-2-氯-1-（31-氯苯基）乙醇; （2）活性最佳pH：5.0〜6.0; （3）最适温度为40℃〜50℃。 （4）分子量：约40,000，通过凝胶过滤分析测定，约30,000，通过SDS聚丙烯酰胺凝胶电泳分析测定。 本发明还涉及包含序列表中SEQ ID NO：1所示氨基酸序列的多肽，编码所述多肽的多核苷酸，以及以高水平产生所述多肽的转化体。
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![Process for preparing optically active 2-[6-(hydroxy-methyl)-1,3-dioxan-4-yl] acetic acid derivatives](/abs-image/US/2005/04/14/US20050080277A1/abs.jpg.150x150.jpg)
5.发明申请Process for preparing optically active 2-[6-(hydroxy-methyl)-1,3-dioxan-4-yl] acetic acid derivatives 失效光学活性的2- [6-（羟基 - 甲基）-1,3-二恶烷-4-基]乙酸衍生物的制备方法公开(公告)号：US20050080277A1
公开(公告)日：2005-04-14
申请号：US10048553
申请日：2001-06-05
IPC分类号： C07D319/06 , C12P7/42 , C12P17/06
CPC分类号： C07D319/06 , C12P7/42 , C12P17/06
摘要： The present invention is to provide a production technology by which an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative, which are of value as pharmaceutical intermediates, can be produced from inexpensive and readily available starting materials without using any extraordinary equipment such as an ultra-low-temperature reactor. The present invention is a production process of an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative which comprises reacting an enolate, prepared by permitting a base or a 0-valent metal to act on an acetic acid ester derivative with (S)-β-hydroxy-γ-butyrolactone at a temperature not lower than −30° C. to give a dihydroxyoxohexanoic acid derivative, treating the same with an acylating agent in the presence of a base to produce a dihydroxyoxohexanoic acid monoacyl derivative, reducing this compound with a microorganism to produce a trihydroxyhexanoic acid monoacyl derivative, treating this compound with an acetal-forming reagent in the presence of an acid catalyst to produce an acyloxymethyldioxanylacetic acid derivative, and finally, subjecting this compound to solvolysis in the presence of a base.
摘要翻译： 本发明提供一种生产技术，通过该技术，可以以廉价的方式生产价值为医药中间体的光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物 和容易获得的起始材料，而不使用任何非常设备，例如超低温反应器。 本发明是光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物的制备方法，该方法包括使通过使碱或0价金属 在不低于-30℃的温度下用（S）-β-羟基-γ-丁内酯在乙酸酯衍生物上作用，得到二羟基氧代己酸衍生物，在酰化剂存在下用酰化剂处理 碱化以制备二羟基氧己基单酰基衍生物，用微生物还原该化合物以产生三羟基己酸单酰基衍生物，在酸催化剂存在下用缩醛形成试剂处理该化合物，得到酰氧基甲基二恶烷基乙酸衍生物，最后， 该化合物在碱存在下溶剂解。
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![Process for preparing optically active 2-[6-(hydroxy-methyl)-1,3-dioxan-4-yl] acetic acid derivatives](/abs-image/US/2006/08/22/US07094594B2/abs.jpg.150x150.jpg)
6.发明授权Process for preparing optically active 2-[6-(hydroxy-methyl)-1,3-dioxan-4-yl] acetic acid derivatives 失效光学活性的2- [6-（羟基 - 甲基）-1,3-二恶烷-4-基]乙酸衍生物的制备方法公开(公告)号：US07094594B2
公开(公告)日：2006-08-22
申请号：US10048553
申请日：2001-06-05
IPC分类号： C12P41/00
CPC分类号： C07D319/06 , C12P7/42 , C12P17/06
摘要： The present invention is to provide a production technology by which an optically active 2-[6-(hydroxymethyl)-1, 3-dioxan-4-yl]acetic acid derivative, which are of value as pharmaceutical intermediates, can be produced from inexpensive and readily available starting materials without using any extraordinary equipment such as an ultra-low-temperature reactor.The present invention is a production process of an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative which comprises reacting an enolate, prepared by permitting a base or a 0-valent metal to act on an acetic acid ester derivative with (S)-β-hydroxy-γ-butyrolactone at a temperature not lower than −30° C. to give a dihydroxyoxohexanoic acid derivative, treating the same with an acylating agent in the presence of a base to produce a dihydroxyoxohexanoic acid monoacyl derivative, reducing this compound with a microorganism to produce a trihydroxyhexanoic acid monoacyl derivative, treating this compound with an acetal-forming reagent in the presence of an acid catalyst to produce an acyloxymethyldioxanylacetic acid derivative, and finally, subjecting this compound to solvolysis in the presence of a base.
摘要翻译： 本发明提供一种生产技术，通过该技术，可以从廉价的方式制备价值为药物中间体的光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物 和容易获得的起始材料，而不使用任何非常设备，例如超低温反应器。 本发明是光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物的制备方法，该方法包括使通过使碱或0价金属 在不低于-30℃的温度下用（S）-β-羟基-γ-丁内酯在乙酸酯衍生物上作用，得到二羟基氧代己酸衍生物，在酰化剂存在下用酰化剂处理 碱化以制备二羟基氧己基单酰基衍生物，用微生物还原该化合物以产生三羟基己酸单酰基衍生物，在酸催化剂存在下用缩醛形成试剂处理该化合物，得到酰氧基甲基二恶烷基乙酸衍生物，最后， 该化合物在碱存在下溶剂解。
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