公开(公告)号：US06696599B2

公开(公告)日：2004-02-24

申请号：US10437058

申请日：2003-05-14

申请人： Antonia Jekkel ,  Attila Konya ,  Istvan Barta ,  Eva Ilkoy ,  Gyorgy Somogyi ,  Gabor Ambrus ,  Gyula Horvath ,  Karoly Albrecht ,  Istvan Szabo ,  Julianna Mozes Nee Suto ,  Janso Salat ,  Attila Andor ,  Laszlo Birincsik ,  Sandor Boros ,  Ildiko Lang ,  Margit Bidlo Nee Igloy

发明人： Antonia Jekkel ,  Attila Konya ,  Istvan Barta ,  Eva Ilkoy ,  Gyorgy Somogyi ,  Gabor Ambrus ,  Gyula Horvath ,  Karoly Albrecht ,  Istvan Szabo ,  Julianna Mozes Nee Suto ,  Janso Salat ,  Attila Andor ,  Laszlo Birincsik ,  Sandor Boros ,  Ildiko Lang ,  Margit Bidlo Nee Igloy

IPC分类号： C07C6702

CPC分类号： C12R1/645 ,  C12P7/62

摘要： The present invention relates to a new microbial process for the preparation of the compound formula (I) from a compound of general formula (II) wherein R stands for an alkali metal or ammonium ion, by the submerged cultivation of a mold strain able to 6&bgr;-hydroxylate a compound of the Formula (II) in aerobic fermentation and by the separation and purification of the product of Formula (I) formed in the course of the bioconversion. The process comprises cultivating a strain of Mortierella maculata filamentous mold species that is able to 6&bgr;-hydroxylate a compound of the general Formula (II), on a nutrient medium containing assimilable carbon and nitrogen sources and mineral salts and separating the product formed from the fermentation broth, then isolating the compound of formula (I) and purifying the same. Novel strains of Mortierella maculata are also disclosed.

摘要翻译： 本发明涉及一种由通式（II）的化合物制备式（I）化合物的新的微生物方法，其中R代表碱金属或铵离子，通过浸没式培养能够提供6β 在需氧发酵中通过分解和纯化在生物转化过程中形成的式（I）的产物来氢化式（II）化合物。 该方法包括在含有可吸收的碳和氮源和矿物盐的营养培养基上培养能够将通式（II）的化合物6β-羟基化的高山被孢霉丝状菌种的菌株，并分离由发酵形成的产物 肉汤，然后分离式（I）化合物并纯化。 还公开了高山被孢霉的新型菌株。

公开(公告)号：US06750366B2

公开(公告)日：2004-06-15

申请号：US10011176

申请日：2001-12-05

申请人： Antonia Jekkel ,  Attila Konya ,  Istvan Barta ,  Eva Ilkoy ,  Gyorgy Somogyi ,  Gabor Ambrus ,  Gyula Horvath ,  Karoly Albrecht ,  Istvan Szabo ,  Julianna Mozes Nee Suto ,  Janso Salat ,  Attila Andor ,  Laszlo Birinesik ,  Sandor Boros ,  Ildiko Lang ,  Margit Bidlo Nee Igloy

发明人： Antonia Jekkel ,  Attila Konya ,  Istvan Barta ,  Eva Ilkoy ,  Gyorgy Somogyi ,  Gabor Ambrus ,  Gyula Horvath ,  Karoly Albrecht ,  Istvan Szabo ,  Julianna Mozes Nee Suto ,  Janso Salat ,  Attila Andor ,  Laszlo Birinesik ,  Sandor Boros ,  Ildiko Lang ,  Margit Bidlo Nee Igloy

IPC分类号： C07C6902

CPC分类号： C12R1/645 ,  C12P7/62

摘要： The present invention relates to a new microbial process for the preparation of the compound formula (I): from a compound of general formula (II): wherein R stands for an alkali metal or ammonium ion, by the submerged cultivation of a mold strain able to 6&bgr;-hydroxylate a compound of the Formula (II) in aerobic fermentation and by the separation and purification of the product of Formula (I) formed in the course of the bioconversion. The process comprises cultivating a strain of Mortierella maculata filamentous mold species that is able to 6&bgr;-hydroxylate a compound of the general Formula (II), on a nutrient medium containing assimilable carbon and nitrogen sources and mineral salts and separating the product formed from the fermentation broth, then isolating the compound of formula (I) and purifying the same. Novel strains of Mortierella maculata are also disclosed.

摘要翻译： 本发明涉及一种制备式（I）化合物的新的微生物方法：由通式（II）的化合物：其中R代表碱金属或铵离子，通过浸没式培养可变形的模具 在有氧发酵中通过分解和纯化在生物转化过程中形成的式（I）的产物来将式（II）的化合物改性为6β-羟基化。 该方法包括在含有可吸收的碳和氮源和矿物盐的营养培养基上培养能够将通式（II）的化合物6β-羟基化的高山被孢霉丝状菌种的菌株，并分离由发酵形成的产物 肉汤，然后分离式（I）化合物并纯化。 还公开了高山被孢霉的新型菌株。

公开(公告)号：US06682913B1

公开(公告)日：2004-01-27

申请号：US09497805

申请日：2000-02-03

申请人： Antonia Jekkel ,  Attila Konya ,  Istvan Barta ,  Eva Ilkoy ,  Gyorgy Somogyi ,  Gabor Ambrus ,  Gyula Horvath ,  Karoly Albrecht ,  Istvan Szabo ,  Julianna Mozes nee Suto ,  Janso Salat ,  Attila Andor ,  Laszlo Birincsik ,  Sandor Boros ,  Ildiko Lang ,  Margit Bidlo nee Igloy

发明人： Antonia Jekkel ,  Attila Konya ,  Istvan Barta ,  Eva Ilkoy ,  Gyorgy Somogyi ,  Gabor Ambrus ,  Gyula Horvath ,  Karoly Albrecht ,  Istvan Szabo ,  Julianna Mozes nee Suto ,  Janso Salat ,  Attila Andor ,  Laszlo Birincsik ,  Sandor Boros ,  Ildiko Lang ,  Margit Bidlo nee Igloy

IPC分类号： C12P762

CPC分类号： C12R1/645 ,  C12P7/62

摘要： The present invention relates to a new microbial process for the preparation of the compound formula (I) from a compound of general formula (II) wherein R stands for an alkali metal or ammonium ion, by the submerged cultivation of a mold strain able to 6&bgr;-hydroxylate a compound of the Formula (II) in aerobic fermentation and by the separation and purification of the product of Formula (I) formed in the course of the bioconversion. The process comprises cultivating a strain of Mortierella maculata filamentous mold species that is able to 6&bgr;-hydroxylate a compound of the general Formula (II), on a nutrient medium containing assimilable carbon and nitrogen sources and mineral salts and separating the product formed from the fermentation broth, then isolating the compound of formula (I) and purifying the same. Novel strains of Mortierella maculata are also disclosed.

公开(公告)号：US06245921B1

公开(公告)日：2001-06-12

申请号：US09497806

申请日：2000-02-03

申请人： Istvan Barta ,  Aniko Tegdes ,  Valeria Szell ,  Csaba Szabo ,  Edit Nagy Nee Arvai ,  Vilmos Keri ,  David Leonov ,  IIdiko Lang ,  Margit Bidlo Nee Igloy ,  Gyula Jerkovich ,  Janos Salat

发明人： Istvan Barta ,  Aniko Tegdes ,  Valeria Szell ,  Csaba Szabo ,  Edit Nagy Nee Arvai ,  Vilmos Keri ,  David Leonov ,  IIdiko Lang ,  Margit Bidlo Nee Igloy ,  Gyula Jerkovich ,  Janos Salat

IPC分类号： C07D31500

CPC分类号： C12P17/162

摘要： A process for the isolation of the pseudomonic acid A antibiotic of pharmaceutical quality from the culture broth of one of the pseudomonic acid A-producing species of the Pseudomonas bacterium genus comprising the extraction of the biosynthesized pseudomonic acid A from the culture broth at acidic pH with a chlorinated aliphatic hydrocarbon or isobutyl acetate, followed by purification, is disclosed. The invention includes processes for purification of the isolated pseudomonic acid A, including (a) by the distribution of the evaporated extract residue between the aqueous-alcohol and some aliphatic or aromatic hydrocarbon, and then the extraction of the increased water-containing aqueous-alcoholic phase with methylene chloride, ethyl acetate, or isobutyl acetate; (b) by the extraction of the extract with aqueous ammonium hydrogen carbonate, alkali metal hydroxide or ammonium hydroxide solution and the acidification of the resulting alkaline aqueous extract, then reextraction again with a chlorinated aliphatic hydrocarbon or isobutyl acetate; and (c) by the concentration of the extract and the recrystallization of the crystalline pseudomonic acid A in a mixture of isobutyl acetate and petroleum ether, or acetonitrile, or aqueous acetonitrile.

摘要翻译： 从假单胞菌属的假单胞菌素A产生物种之一的培养液中分离出假单胞菌A抗生素药物质量的方法，包括在酸性pH下从培养液中提取生物合成的假单胞菌酸A， 公开了氯化脂族烃或乙酸异丁酯，然后纯化。 本发明包括纯化分离的假单胞菌酸A的方法，包括（a）通过在含水醇和某些脂族或芳族烃之间分配蒸发的提取物残渣，然后提取含水的含水醇 与二氯甲烷，乙酸乙酯或乙酸异丁酯反应; （b）通过用碳酸氢铵水溶液，碱金属氢氧化物或氢氧化铵溶液萃取提取物，并将得到的碱性水提取物酸化，然后用氯化脂族烃或乙酸异丁酯再次萃取; 和（c）通过提取物的浓度和结晶假单胞菌酸A在乙酸异丁酯和石油醚或乙腈或乙腈水溶液的混合物中的重结晶。

公开(公告)号：US4579954A

公开(公告)日：1986-04-01

申请号：US604385

申请日：1984-04-27

申请人： Kalman Harsanyi ,  Gyorgy Domany ,  Oszkar Fuchs ,  Lajos Toldy ,  Gyorgy Fekete ,  Endre Kasztreiner ,  Bela Hegedus ,  Ferenc Morasz ,  Andras Rado ,  Tibor Lang ,  Arpad Lazar ,  Eva Csongor ,  Tibor Balogh ,  Janos Borvendeg ,  Jozsef Reiter ,  Tibor Somogyi ,  Margit Bidlo nee Igloy

发明人： Kalman Harsanyi ,  Gyorgy Domany ,  Oszkar Fuchs ,  Lajos Toldy ,  Gyorgy Fekete ,  Endre Kasztreiner ,  Bela Hegedus ,  Ferenc Morasz ,  Andras Rado ,  Tibor Lang ,  Arpad Lazar ,  Eva Csongor ,  Tibor Balogh ,  Janos Borvendeg ,  Jozsef Reiter ,  Tibor Somogyi ,  Margit Bidlo nee Igloy

IPC分类号： A61K31/415 ,  A61P1/04 ,  C07D233/54 ,  C07D233/64

CPC分类号： C07D233/64

摘要： The invention relates to the new monohydrate of N-methyl-N'-{2-[(5-methylimidazol-4-yl)-methylthio]-ethyl}-N"-cyanoguanidine (cimetidine), a histamine-H.sub.2 receptor antagonist which is called N-methyl-N'-{2-[(5-methylimidazol-4-yl)-methylthio]-ethyl}-N"-cyanoguanidine H (cimetidine H) as well as to a process for the preparation of same, which comprises pouring a hot, homogeneous aqueous solution of N-methyl-N'-{2-[(5-methylimidazol-4-yl)-methylthio]-ethyl}-N"-cyanoguanidine, optionally containing also methylamine, onto ice and separating the N-methyl-N'-{2-[(5-methylimidazol-4-yl)-methylthio]-ethyl}-N"-cyanoguanidine monohydrate.

摘要翻译： 本发明涉及N-甲基-N' - {2 - [（5-甲基咪唑-4-基） - 甲硫基] - 乙基} -N' - 氰基胍（西咪替丁），组胺-H 2受体 称为N-甲基-N' - {2 - [（5-甲基咪唑-4-基） - 甲硫基] - 乙基} -N'-氰基胍脒H（西咪替丁H）的方法以及 其包括将热的均匀的N-甲基-N' - {2 - [（5-甲基咪唑-4-基） - 甲硫基] - 乙基} -N“ - 氰基胍的水溶液，任选地含有 并将甲胺加到冰上并分离N-甲基-N' - {2 - [（5-甲基咪唑-4-基） - 甲硫基] - 乙基} -N'-氰基胍一水合物。