公开(公告)号：US5565345A

公开(公告)日：1996-10-15

申请号：US380334

申请日：1995-01-30

申请人： Yoshihiko Yasohara ,  Yoshiko Tari ,  Noboru Ueyama ,  Junzo Hasegawa ,  Satomi Takahashi

发明人： Yoshihiko Yasohara ,  Yoshiko Tari ,  Noboru Ueyama ,  Junzo Hasegawa ,  Satomi Takahashi

IPC分类号： A61K31/35 ,  A61P27/02 ,  A61P27/06 ,  C07D495/04 ,  C12P17/18 ,  C12P41/00 ,  C12R1/645 ,  C12R1/72 ,  C12R1/74 ,  C12R1/78 ,  C12R1/84 ,  C12R1/85 ,  C12R1/865 ,  C12P11/00 ,  C07D409/04 ,  C12P17/00

CPC分类号： C07D495/04 ,  C12P17/185 ,  C12P41/002

摘要： A process for preparing 5,6-dihydro-4-hydroxy-(S)-6-methyl-thieno[2,3-b]thiopyran-7,7-dioxide having the formula (II): ##STR1## which comprises subjecting 5,6-dihydro-4-oxo-(S)-6-methyl-thieno[2,3-b]thiopyran-7,7-dioxide having the formula (I): ##STR2## to the action of a microorganism to reduce the thienothiopyran derivative having the formula (I), and collecting 5,6-dihydro-4-hydroxy-(S)-6-methyl-thieno-[2,3-b]thiopyran-7,7-dioxide having the formula (II) from the reaction mixture, wherein said microorganism belongs to the genus selected from the group consisting of Ambrosiozyma, Arthroascus, Ashbya, Candida, Cryptococcus, Hansenula, Kluyveromyces, Lipomyces, Lodderomyces, Metschnikowia, Pachysolen, Pichia, Rhodosporidium, Rhodotorula, Saccharomyces, Saccharomycopsis, Schwanniomyces, Sporidiobolus, Spolobolomyces, Stephanoascus, Trigonopsis, Trichosporon and Wingea, according to which, a simple and effective. process for preparing 5,6-dihydro-4-hydroxy-(S)-6-methyl-thieno-[2,3-b]thiopyran-7,7-dioxide.

摘要翻译： 具有式（II）的5,6-二氢-4-羟基 - （S）-6-甲基 - 噻吩并[2,3-b]噻喃-7,7-二氧化物的制备方法： 其包括将具有式（I）的5,6-二氢-4-氧代 - （S）-6-甲基 - 噻吩并[2,3-b]噻喃-7,7-二氧化物：（I） 微生物降低具有式（I）的噻吩并吡喃衍生物的作用，并收集5,6-二氢-4-羟基 - （S）-6-甲基 - 噻吩并[2,3-b]噻喃-7， 其中所述微生物属于选自Ambrosiozyma，Arthroascus，Ashbya，Candida，Cryptococcus，Hansenula，Kluyveromyces，Lipomyces，Lodderomyces，Metschnikowia，Pachysolen，Pichia ，Rhodosporidium，Rhodotorula，Saccharomyces，Saccharomycopsis，Schwanniomyces，Sporidiobolus，Spolobolomyces，Stephanoascus，Trigonopsis，Trichosporon和Wingea，据此，一个简单有效的。 制备5,6-二氢-4-羟基 - （S）-6-甲基 - 噻吩并[2,3-b]噻喃-7,7-二氧化物的方法。

公开(公告)号：US20050080277A1

公开(公告)日：2005-04-14

申请号：US10048553

申请日：2001-06-05

申请人： Akira Nishiyama ,  Miho Horikawa ,  Yoshihiko Yasohara ,  Noboru Ueyama ,  Kenji Inoue

发明人： Akira Nishiyama ,  Miho Horikawa ,  Yoshihiko Yasohara ,  Noboru Ueyama ,  Kenji Inoue

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。

公开(公告)号：US06903225B2

公开(公告)日：2005-06-07

申请号：US10242453

申请日：2002-09-13

申请人： Noriyuki Kizaki ,  Yukio Yamada ,  Yoshihiko Yasohara ,  Akira Nishiyama ,  Makoto Miyazaki ,  Masaru Mitsuda ,  Takeshi Kondo ,  Noboru Ueyama ,  Kenji Inoue

发明人： Noriyuki Kizaki ,  Yukio Yamada ,  Yoshihiko Yasohara ,  Akira Nishiyama ,  Makoto Miyazaki ,  Masaru Mitsuda ,  Takeshi Kondo ,  Noboru Ueyama ,  Kenji Inoue

IPC分类号： C07C67/343 ,  C07C253/30 ,  C07C255/21 ,  C07D319/06 ,  C12P7/62 ,  C12P1/04 ,  C12P17/06

CPC分类号： C07D319/06 ,  C07B2200/07 ,  C07C67/343 ,  C07C253/30 ,  C12P7/62 ,  C07C69/716 ,  C07C255/21

摘要： This invention provides a process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives, which are of value as intermediates of drugs, from inexpensive starting materials without using any special equipment such as that required for super-low temperature reactions.A process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives which comprises reacting an acetic acid derivative at a temperature of not less than −30° C. with an enolate prepared by permitting either a base or a metal having a valency of 0 to act on the derivative to produce a hydroxyoxohexanoic acid derivative, reducing this compound with the aid of a strain of microorganism to provide a halomethyldioxanylacetic acid derivative, treating this compound with an acetalizing agent in the presence of an acid catalyst to provide a halomethyl-dioxanylacetic acid derivative, reacted with an acyloxylating agent to provide a acyloxymethyldioxanylacetic acid derivative, and subjecting this compound to solvolysis in the presence of a base.

摘要翻译： 本发明提供了从廉价起始原料生产具有价值作为药物中间体的光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物的方法，而不使用任何特殊设备 例如超低温反应所需的。 一种制备光学活性的2- [6-（羟基甲基）-1,3-二恶烷-4-基]乙酸衍生物的方法，其包括使不饱和-30℃的乙酸衍生物与烯醇化物 通过使碱金属或0价金属作用于衍生物以制备羟基己酸衍生物而制备，借助于微生物菌株还原该化合物以提供卤代甲基二恶烷基乙酸衍生物，用缩醛化处理该化合物 在酸催化剂存在下，提供卤代甲基 - 二恶烷基乙酸衍生物，与酰氧基化剂反应，得到酰氧基甲基二恶烷基乙酸衍生物，并在碱的存在下使其溶解。

公开(公告)号：US06472544B1

公开(公告)日：2002-10-29

申请号：US09509998

申请日：2000-08-16

申请人： Noriyuki Kizaki ,  Yukio Yamada ,  Yoshihiko Yasohara ,  Akira Nishiyama ,  Makoto Miyazaki ,  Masaru Mitsuda ,  Takeshi Kondo ,  Noboru Ueyama ,  Kenji Inoue

发明人： Noriyuki Kizaki ,  Yukio Yamada ,  Yoshihiko Yasohara ,  Akira Nishiyama ,  Makoto Miyazaki ,  Masaru Mitsuda ,  Takeshi Kondo ,  Noboru Ueyama ,  Kenji Inoue

IPC分类号： C07D31906

CPC分类号： C07D319/06 ,  C07B2200/07 ,  C07C67/343 ,  C07C253/30 ,  C12P7/62 ,  C07C69/716 ,  C07C255/21

摘要： This invention provides a process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives, which are of value as intermediates of drugs, from inexpensive starting materials without using any special equipment such as that required for super-low temperature reactions. A process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives which comprises reacting an acetic acid derivative at a temperature of not less than −30° C. with an enolate prepared by permitting either a base or a metal having a valency of 0 to act on the derivative to produce a hydroxyoxohexanoic acid derivative, reducing this compound with the aid of a strain of microorganism to provide a halomethyldioxanylacetic acid derivative, treating this compound with an acetalizing agent in the presence of an acid catalyst to provide a halomethyldioxanylacetic acid derivative, reacted with an acyloxylating agent to provide a acyloxymethyldioxanylacetic acid derivative, and subjecting this compound to solvolysis in the presence of a base.

摘要翻译： 本发明提供了从廉价起始原料生产具有价值作为药物中间体的光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物的方法，而不使用任何特殊设备 例如超低温反应所需的方法。一种制备光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物的方法，其包括在不是的温度下使乙酸衍生物反应 小于-30℃，通过使碱金属或化合价为0的金属作用于衍生物以制备羟基氧代己酸衍生物而制备的烯醇化物，借助于微生物菌株还原该化合物以提供 卤甲基二恶烷基乙酸衍生物，在酸催化剂存在下用缩醛化剂处理该化合物，得到卤代甲基二恶烷基乙酸衍生物，与酰氧基化剂反应，得到酰氧基甲基二恶烷基乙酸 在碱的存在下，将该化合物施用于溶剂分解。

公开(公告)号：US07094594B2

公开(公告)日：2006-08-22

申请号：US10048553

申请日：2001-06-05

申请人： Akira Nishiyama ,  Miho Horikawa ,  Yoshihiko Yasohara ,  Noboru Ueyama ,  Kenji Inoue

发明人： Akira Nishiyama ,  Miho Horikawa ,  Yoshihiko Yasohara ,  Noboru Ueyama ,  Kenji Inoue

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。

公开(公告)号：US5616726A

公开(公告)日：1997-04-01

申请号：US392826

申请日：1995-06-21

申请人： Masaru Mitsuda ,  Shigeo Hayashi ,  Junzo Hasegawa ,  Noboru Ueyama ,  Takehisa Ohashi ,  Masakatsu Shibasaki

发明人： Masaru Mitsuda ,  Shigeo Hayashi ,  Junzo Hasegawa ,  Noboru Ueyama ,  Takehisa Ohashi ,  Masakatsu Shibasaki

IPC分类号： C07C213/02 ,  C07C215/28 ,  C07C227/02 ,  C07C229/34 ,  C07C269/02 ,  C07C271/16

CPC分类号： C07C269/02 ,  C07C213/02 ,  C07C215/28 ,  C07C227/02 ,  C07C229/34 ,  C07C271/16 ,  Y02P20/55

摘要： An object of the present invention is to provide a safe method of commercially producing optically active aminoalcohol derivatives, which serve as intermediates for the synthesis of medicinal chemicals such as the immunopotentiating anticancer agent bestatin, in a simple and easy manner in high yields and with high levels of selectivity.The present invention consists in a method of producing 3-amino-1-nitro-4-phenyl-2-butanol derivatives of the general formula (1) ##STR1## wherein R.sup.1 and R.sup.2 each independently represents a hydrogen atom or an amino group protecting group, and a method of producing 3-amino-2-hydroxy-4-phenylbutyric acid derivatives derivable therefrom.

摘要翻译： PCT No.PCT / JP94 / 01049 Sec。 371日期：1995年6月21日 102（e）1995年6月21日PCT PCT 1994年6月29日PCT公布。 出版物WO95 / 01323 日本1995年1月12日本发明的目的是提供一种安全的商业生产光学活性氨基醇衍生物的方法，其用作合成药物的中间体，例如免疫增强抗癌药的美白蛋白，简单易用 高产量和高选择性。 本发明在于制备通式（1）的3-氨基-1-硝基-4-苯基-2-丁醇衍生物的方法，其中R1和R2各自独立地表示氢原子或 氨基保护基，以及由其衍生的3-氨基-2-羟基-4-苯基丁酸衍生物的方法。

公开(公告)号：USRE36718E

公开(公告)日：2000-05-30

申请号：US280853

申请日：1999-03-30

申请人： Masaru Mitsuda ,  Shigeo Hayashi ,  Junzo Hasegawa ,  Noboru Ueyama ,  Takehisa Ohashi ,  Masakatsu Shibasaki

发明人： Masaru Mitsuda ,  Shigeo Hayashi ,  Junzo Hasegawa ,  Noboru Ueyama ,  Takehisa Ohashi ,  Masakatsu Shibasaki

IPC分类号： C07C213/02 ,  C07C215/28 ,  C07C227/02 ,  C07C229/34 ,  C07C269/02 ,  C07C271/16

CPC分类号： C07C269/02 ,  C07C213/02 ,  C07C215/28 ,  C07C227/02 ,  C07C229/34 ,  C07C271/16 ,  Y02P20/55

摘要： An object of the present invention is to provide a safe method of commercially producing optically active aminoalcohol derivatives, which serve as intermediates for the synthesis of medicinal chemicals such as the immunopotentiating anticancer agent bestatin, in a simple and easy manner in high yields and with high levels of selectivity.The present invention consists in a method of producing 3-amino-1-nitro-4-phenyl-2-butanol derivatives of the general formula (1) ##STR1## wherein R.sup.1 and R.sup.2 each independently represents a hydrogen atom or an amino group protecting group, and a method of producing 3-amino-2-hydroxy-4-phenylbutyric acid derivatives derivable therefrom.

摘要翻译： PCT No.PCT / JP94 / 01049 Sec。 371日期：1995年6月21日 102（e）1995年6月21日PCT PCT 1994年6月29日PCT公布。 出版物WO95 / 01323 日本1995年1月12日本发明的目的是提供一种安全的商业生产光学活性氨基醇衍生物的方法，其用作合成药物的中间体，例如免疫增强抗癌药的美白蛋白，简单易用 高产量和高选择性。 本发明在于制备通式（1）的3-氨基-1-硝基-4-苯基-2-丁醇衍生物的方法，其中R 1和R 2各自独立地表示氢原子或氨基保护基，和 制备可从其衍生的3-氨基-2-羟基-4-苯基丁酸衍生物的方法。

公开(公告)号：US5079382A

公开(公告)日：1992-01-07

申请号：US617345

申请日：1990-11-23

申请人： Naoaki Taoka ,  Kenji Inoue ,  Shigeo Hayashi ,  Noboru Ueyama ,  Satomi Takahashi

发明人： Naoaki Taoka ,  Kenji Inoue ,  Shigeo Hayashi ,  Noboru Ueyama ,  Satomi Takahashi

IPC分类号： C07C303/30 ,  C07C309/65 ,  C07C309/66 ,  C07C309/73 ,  C07D303/40

CPC分类号： C07D303/40 ,  C07C309/65 ,  C07C309/73

摘要： A 3,4-epoxybutyrate of the formula: ##STR1## wherein R.sup.1 is an alkyl or aralkyl group is efficiently prepared by a process comprising steps of:(a) reacting 3,4-dihydroxybutyronitrile of the formula: ##STR2## with a sulfonyl chloride of the formula: R.sup.2 --SO.sub.2 --Cl wherein R.sup.2 is an alkyl group or a phenyl group which may be substituted in the presence of a base to obtain a compound of the formula: ##STR3## (b) reacting the compound prepared in the step (a) with an alcohol of the formula: R.sup.1 --OH in the presence of an acid to obtain a compound of the formula: ##STR4## and (c) reacting the compound prepared in the step (b) with a base to obtain the 3,4-epoxybutyrate.

公开(公告)号：US5214197A

公开(公告)日：1993-05-25

申请号：US724728

申请日：1991-07-02

申请人： Shigeo Hayashi ,  Noboru Ueyama ,  Kenji Inoue ,  Teruyoshi Koga ,  Satomi Takahashi

发明人： Shigeo Hayashi ,  Noboru Ueyama ,  Kenji Inoue ,  Teruyoshi Koga ,  Satomi Takahashi

IPC分类号： C07C69/675 ,  C07C69/738

CPC分类号： C07C69/738 ,  C07C69/675 ,  Y02P20/55

摘要： A novel 2,4-dihydroxyadipic acid derivative of the formula: ##STR1## wherein R.sup.1 and R.sup.4 are the same or different and each a hydrogen atom, an alkyl group, an aralkyl group, an aryl group or a silyl group, and R.sup.2 and R.sup.3 are the same or different and each a hydrogen atom or a protective group of a hydroxy group or together form a ring, which is useful as a common intermediate in the synthesis of HMG-CoA reductase inhibitor.

公开(公告)号：US5214199A

公开(公告)日：1993-05-25

申请号：US755496

申请日：1991-08-30

申请人： Teruyoshi Koga ,  Noboru Ueyama ,  Kenji Inoue ,  Satomi Takahashi

发明人： Teruyoshi Koga ,  Noboru Ueyama ,  Kenji Inoue ,  Satomi Takahashi

IPC分类号： B01J31/02 ,  C07B61/00 ,  C07C67/08 ,  C07C67/287 ,  C07C69/38 ,  C07C69/635

CPC分类号： C07C67/08

摘要： A malonic monoester is prepared in a good yield by a single step reaction by reacting malonic acid with an alcohol in the presence of a base and an activator of malonic acid selected from the group consisting of an acyl halide or halocarbonate and an acid anhydride or dicarbonate.