公开(公告)号：USRE30413E

公开(公告)日：1980-10-07

申请号：US41995

申请日：1979-05-24

申请人： Hamao Umezawa ,  Yasushi Takahashi ,  Tadashi Shirai ,  Akio Fujii

发明人： Hamao Umezawa ,  Yasushi Takahashi ,  Tadashi Shirai ,  Akio Fujii

IPC分类号： C07K9/00

CPC分类号： C07K9/003 ,  Y10S435/866 ,  Y10S435/886 ,  Y10S435/911 ,  Y10S435/929

摘要： A process for preparing bleomycinic acid having a melting point of 228.degree.-230.degree. C. (decomposition) and an analysis of C: 40.80%, H: 5.29%, N: 16.45%, O: 24.78%, S: 4.53%, Cl: 3.37%, and Cu: 4.78% which is characterized by being soluble in water, difficultly soluble in methanol, acetic acid and dimethylsulfoxide, and insoluble in ethanol, ethyl acetate, acetone and ether, and which tests positive to Pauly and Ehrlich reactions but tests negative to ninhydrin, Sakaguchi, Dragendorf, Tollens, ferric chloride, Fehling and Molish reactions, and which has a maximum ultraviolet absorption spectrum at 246 m.mu. and 292 m.mu. and which has an infrared absorption spectrum bands at 3350, 1720, 1670, 1640, 1580, 1460, 1365, 1050, 770 (cm.sup.-1), and which can be hydrolyzed to yield 2'-(2-aminoethyl)-2,4'-bithiazole-4-carboxylic acid, L-threonine, 4-amino-3-hydroxy-2-methyl-.eta.-valeric acid, .beta.-hydroxy-histidine, .beta.-amino-.beta.-(4-amino-6-carboxy-5-methylpyrimidine-2-yl)-propionic acid, L-.beta.-amino-alanine, L-gulose and 3-O-carbamoyl-D-mannose, which comprises hydrolyzing bleomycin in the presence of a mycelium mass or enzyme.

公开(公告)号：US3932374A

公开(公告)日：1976-01-13

申请号：US479087

申请日：1974-06-13

申请人： Hamao Umezawa ,  Yasushi Takahashi ,  Tadashi Shirai ,  Akio Fujii

发明人： Hamao Umezawa ,  Yasushi Takahashi ,  Tadashi Shirai ,  Akio Fujii

IPC分类号： C07H15/26 ,  C07C103/52 ,  A61K37/00

CPC分类号： C07H15/26

摘要： A process for preparing bleomycinic acid having a melting point of 228.degree.-230.degree.C. (decomposition) and an analysis of C : 40.80%, H : 5.29%, N : 16.45%, O : 24.78%, S : 4.53%, Cl : 3.37%, and Cu : 4.78% which is characterized by being soluble in water, difficultly soluble in methanol, acetic acid and dimethylsulfoxide, and insoluble in ethanol, ethyl acetate, acetone and ether, and which tests positive to Pauly and Ehrlich reactions but tests negative to ninhydrin, Sakaguchi, Dragendorf, Tollens, ferric chloride, Fehling and Molish reactions, and which has a maximum ultraviolet absorption spectrum at 246 m.mu. and 292 m.mu. and which has an infrared absorption spectrum bands at 3350, 1720, 1670, 1640, 1580, 1460, 1365, 1050, 770 (cm.sup.-.sup.1), and which can be hydrolyzed to yield 2'-(2-aminoethyl)-2,4'-bithiazole-4-carboxylic acid, L-threonine, 4-amino-3-hydroxy-2-methyl-.eta.-valeric acid, .beta.-hydroxy-histidine, .beta.-amino-.beta.-(4-amino-6-carboxy-5-methylpyrimidine-2-yl)-propionic acid, L-.beta.-amino-alanine, L-gulose and 3-0-carbamoyl-D-mannose, which comprises hydrolyzing bleomycin in the presence of a mycelium mass or enzyme.

摘要翻译： 制备熔点为228〜-230℃的博来霉素酸（分解），C：40.80％，H：5.29％，N：16.45％，O：24.78％，S：4.53％的分析方法， Cl：3.37％，Cu：4.78％，其特征在于可溶于水，难溶于甲醇，乙酸和二甲基亚砜，不溶于乙醇，乙酸乙酯，丙酮和乙醚，并对Pauly和Ehrlich反应进行检测 但对茚三酮，Sakaguchi，Dragendorf，Tollens，氯化铁，Fehling和Molish反应阴性测试，其最大紫外吸收光谱为246μm和292μm，红外吸收光谱带为3350,1720,1670 ，1640,1580,1460,1365,1050,770（cm -1），并可水解得到2' - （2-氨基乙基）-2,4'-联噻唑-4-羧酸，L- 苏氨酸，4-氨基-3-羟基-2-甲基 - 戊酸，β-羟基 - 组氨酸，β-氨基-β-（4-氨基-6-羧基-5-甲基嘧啶-2-基） - 丙酸 一个 cid，L-β-氨基 - 丙氨酸，L-古洛糖和3-0-氨基甲酰-D-甘露糖，其包括在菌丝体或酶存在下水解博来霉素。

公开(公告)号：US4281180A

公开(公告)日：1981-07-28

申请号：US96693

申请日：1979-11-23

申请人： Hamao Umezawa ,  Takaaki Aoyagi ,  Tadashi Shirai ,  Rinzo Nishizawa ,  Masao Suzuki ,  Tetsushi Saino

发明人： Hamao Umezawa ,  Takaaki Aoyagi ,  Tadashi Shirai ,  Rinzo Nishizawa ,  Masao Suzuki ,  Tetsushi Saino

IPC分类号： A47L13/40 ,  A61K20060101 ,  A61K31/16 ,  A61K31/195 ,  C07C20060101 ,  C07C51/347 ,  C07C233/31 ,  C07C233/47 ,  C07C233/76 ,  C07C233/87 ,  C07C271/22 ,  C07C271/34 ,  C07C271/54 ,  C07D209/48 ,  C07K1/06 ,  C07K5/02 ,  C07K5/06

CPC分类号： C07C237/20 ,  A61K38/00 ,  Y02P20/55

摘要： A process for producing threo-3-amino-2-hydroxybutanoylaminoacetic acids comprises the steps of allowing to react a starting compound represented by the general formula: ##STR1## wherein R.sub.1 represents a naphthyl or a group of the formula: ##STR2## in which R.sub.6 and R.sub.7 represent individually hydrogen, halogen, amino or a protected amino, hydroxy or a protected hydroxy, a lower alkoxy or a lower alkyl and R.sub.2 represents a protected amino, with a starting compound represented by the general formula: ##STR3## wherein R.sub.3 represents hydrogen or an ester residue, to obtain threo-3-protected amino-2-hydroxy-4-oxobutanoic acid or its ester represented by the general formula: ##STR4## wherein R.sub.1, R.sub.2 and R.sub.3 have the same meanings as above, and then reducing the same into threo-3-protected amino-2-hydroxybutanoic acid or its ester represented by the general formula: ##STR5## wherein R.sub.1, R.sub.2 and R.sub.3 have the same meanings as above, and further converting the above compound into 3-amino-2-hydroxybutanoic acid represented by the general formula: ##STR6## wherein R.sub.2 ' represents amino or a protected amino, thereafter condensing the same, in a conventional manner for forming a peptide coupling, with a compound represented by the general formula: ##STR7## wherein R.sub.4 represents an alkyl having 3-4 carbon atom or 3-guanidinopropyl, while previously protecting as required those groups not relevant to the reaction, and removing the protecting groups for the functional groups to produce threo-3-amino-2-hydroxybutanoylaminoacetic acids represented by the general formula: ##STR8## wherein R.sub.1 and R.sub.4 have the same meanings as above. This invention also provides the compounds represented by the general formula (III) as novel intermediates for the above aimed compounds and a process for producing the intermediates.

公开(公告)号：US4453003A

公开(公告)日：1984-06-05

申请号：US336492

申请日：1981-12-31

申请人： Hamao Umezawa ,  Takaaki Aoyagi ,  Tadashi Shirai ,  Rinzo Nishizawa ,  Masao Suzuki ,  Tetsushi Saino

发明人： Hamao Umezawa ,  Takaaki Aoyagi ,  Tadashi Shirai ,  Rinzo Nishizawa ,  Masao Suzuki ,  Tetsushi Saino

IPC分类号： A47L13/40 ,  A61K20060101 ,  A61K31/16 ,  A61K31/195 ,  C07C20060101 ,  C07C51/347 ,  C07C233/31 ,  C07C233/47 ,  C07C233/76 ,  C07C233/87 ,  C07C271/22 ,  C07C271/34 ,  C07C271/54 ,  C07D209/48 ,  C07K1/06 ,  C07K5/02 ,  C07K5/06 ,  C07C101/30

CPC分类号： C07C237/20 ,  A61K38/00 ,  Y02P20/55

摘要： A process for producing threo-3-amino-2-hydroxybutanoylaminoacetic acids comprises the steps of allowing to react a starting compound represented by the general formula: ##STR1## wherein R.sub.1 represents a naphthyl or a group of the formula: ##STR2## in which R.sub.6 and R.sub.7 represent individually hydrogen, halogen, amino or a protected amino, hydroxy or a protected hydroxy, a lower alkoxy or a lower alkyl and R.sub.2 represents a protected amino, with a starting compound represented by the general formula: ##STR3## wherein R.sub.3 represents hydrogen or an ester residue, to obtain threo-3-protected amino-2-hydroxy-4-oxobutanoic acid or its ester represented by the general formula: ##STR4## wherein R.sub.1, R.sub.2 and R.sub.3 have the same meanings as above, and then reducing the same into threo-3-protected amino-2-hydroxybutanoic acid or its ester represented by the general formula: ##STR5## wherein R.sub.1, R.sub.2 and R.sub.3 have the same meanings as above, and further converting the above compound into 3-amino-2-hydroxybutanoic acid represented by the general formula: ##STR6## wherein R.sub.2 ' represents amino or a protected amino, thereafter condensing the same, in a conventional manner for forming a peptide coupling, with a compound represented by the general formula: ##STR7## wherein R.sub.4 represents an alkyl having 3-4 carbon atom or 3-guanidinopropyl, while previously protecting as required those groups not relevant to the reaction, and removing the protecting groups for the functional groups to produce threo-3-amino-2-hydroxybutanoylaminoacetic acids represented by the general formula: ##STR8## wherein R.sub.1 and R.sub.4 have the same meanings as above. This invention also provides the compounds represented by the general formula (III) as novel intermediates for the above aimed compounds and a process for producing the intermediates.

公开(公告)号：US4391986A

公开(公告)日：1983-07-05

申请号：US211035

申请日：1980-11-28

申请人： Hamao Umezawa ,  Takaaki Aoyagi ,  Tadashi Shirai ,  Rinzo Nishizawa ,  Masao Suzuki ,  Tetsushi Saino

发明人： Hamao Umezawa ,  Takaaki Aoyagi ,  Tadashi Shirai ,  Rinzo Nishizawa ,  Masao Suzuki ,  Tetsushi Saino

IPC分类号： A47L13/40 ,  A61K20060101 ,  A61K31/16 ,  A61K31/195 ,  C07C20060101 ,  C07C51/347 ,  C07C233/31 ,  C07C233/47 ,  C07C233/76 ,  C07C233/87 ,  C07C271/22 ,  C07C271/34 ,  C07C271/54 ,  C07D209/48 ,  C07K1/06 ,  C07K5/02 ,  C07K5/06 ,  C07C101/34

CPC分类号： C07C237/20 ,  A61K38/00 ,  Y02P20/55

摘要： Threo-3-protected amino-2-hydroxy-4-oxobutanoic acid or its esters represented by the formula: ##STR1## wherein R.sub.1 represents naphthyl or a group of the formula ##STR2## in which R.sub.6 and R.sub.7 represent individually hydrogen, halogen, amino, an amino protected with acyl, lower alkyloxycarbonyl or carbamoyl, hydroxy or protected with acyl, lower alkyloxycarbonyl or carbamoyl, lower alkoxy, lower alkyl or phenyl group; R.sub.2 represents an amine protected with acyl, lower alkyloxycarbonyl or carbamoyl; and R.sub.3 represents hydrogen, lower alkyl having 1 to 6 carbon atoms or benzyl.

摘要翻译： Threo-3保护的氨基-2-羟基-4-氧代丁酸或其由下式表示的酯：其中R 1表示萘基或式（VI）的基团，其中R 6和R 7分别表示氢，卤素， 氨基，被酰基保护的氨基，低级烷氧基羰基或氨基甲酰基，羟基或用酰基保护，低级烷氧基羰基或氨基甲酰基，低级烷氧基，低级烷基或苯基; R2代表被酰基，低级烷氧基羰基或氨基甲酰基保护的胺; 并且R 3表示氢，具有1至6个碳原子的低级烷基或苄基。

公开(公告)号：US4107203A

公开(公告)日：1978-08-15

申请号：US822826

申请日：1977-08-08

申请人： Yasuhisa Tashiro ,  Hideo Sugimura ,  Toshiaki Arai ,  Masao Suzuki ,  Tadashi Shirai

发明人： Yasuhisa Tashiro ,  Hideo Sugimura ,  Toshiaki Arai ,  Masao Suzuki ,  Tadashi Shirai

IPC分类号： C07B57/00 ,  C07C101/04

CPC分类号： C07B57/00

摘要： In order to separate optically active D- or L-.alpha.-phenylglycine hydrochloride from a supersaturated solution of DL-.alpha.-phenylglycine hydrochloride seed crystals of the desired D- or L-isomer are added to the solution in the presence of a metal chloride.

摘要翻译： 为了从DL-α-苯基甘氨酸盐的过饱和溶液中分离光学活性的D-或L-α-苯基甘氨酸盐酸盐，将所需的D-或L-异构体的晶体在金属氯化物的存在下加入到溶液中。

公开(公告)号：US4115439A

公开(公告)日：1978-09-19

申请号：US670420

申请日：1976-03-25

申请人： Shigeru Aoki ,  Yasuhisa Tashiro ,  Yuzo Aboshi ,  Toshiro Narita ,  Tadashi Shirai

发明人： Shigeru Aoki ,  Yasuhisa Tashiro ,  Yuzo Aboshi ,  Toshiro Narita ,  Tadashi Shirai

IPC分类号： C07C227/34 ,  C07B57/00 ,  C07C229/36 ,  C07C101/04 ,  C07C143/26

CPC分类号： C07B57/00

摘要： DL- .alpha.-phenylglycine can be combined with benzene-sulfonic acid, p-ethylbenzenesulfonic acid or m-xylenesulfonic acid to give the salt. The salt of the racemate may be more soluble in a sulfuric acid solution than the salt of the optically active isomer by suitably choosing the concentration of the sulfuric acid solution, and then the optical resolution by fractional crystallization is carried out. The D- or L- .alpha.-phenylglycine sulfonate is easily liberated of the sulfonic acid portion to give optically active D- or L- .alpha.-phenylglycine.

摘要翻译： DL-α-苯基甘氨酸可与苯磺酸，对乙基苯磺酸或间二甲苯磺酸组合，得到盐。 通过适当选择硫酸溶液的浓度，外消旋体的盐可以比硫酸溶液更好地溶解于光学活性异构体的盐中，然后通过分级结晶进行光学拆分。 D-或L-α-苯基甘氨酸磺酸盐容易释放出磺酸部分，得到光学活性的D-或L-α-苯基甘氨酸。

公开(公告)号：US5240944A

公开(公告)日：1993-08-31

申请号：US665662

申请日：1991-03-07

申请人： Tsuyoshi Tomiyama ,  Akira Tomiyama ,  Tadashi Shirai ,  Shuuichi Wakabayashi ,  Tomoyuki Kawai ,  Naoto Ueyama ,  Motoharu Sonegawa

发明人： Tsuyoshi Tomiyama ,  Akira Tomiyama ,  Tadashi Shirai ,  Shuuichi Wakabayashi ,  Tomoyuki Kawai ,  Naoto Ueyama ,  Motoharu Sonegawa

IPC分类号： C07D471/14 ,  C07D487/04 ,  C07D519/00

CPC分类号： C07D471/14 ,  C07D487/04

摘要： Derivatives of cyclic guanidine are disclosed, which are represented by the following formula:A--S--Rwherein A is ##STR1## R.sub.1 represent a lower alkyl or substituted phenyl or unsubstituted phenyl group; R.sub.2 is a lower alkyl; R.sub.3 is H or a lower alkyl; R is lower alkyl, alkenyl, alkynyl, alkanoyl, alkenoyl, dialkylaminoalkyl, cyanoalkyl, alkoxycarbonylalkyl, carboxylalkenyl, alkoxycarbonyl, alkoxyalkylcarbonyl, dialkylaminocarbonyl, dialkylaminothiocarbonyl, phenoxyalkylcarbonyl, piperidinoalkyl, pyridine carbonyl, substituted or unsubstituted benzoyl, or substituted or unsubstituted benzyl group. The compounds of the present invention are useful as anti-ulcerative agents.

摘要翻译： 公开了由下式表示的环状胍的衍生物：A-S-R其中A为低级烷基或取代的苯基或未取代的苯基; R2是低级烷基; R3是H或低级烷基; R是低级烷基，烯基，炔基，烷酰基，烯酰基，二烷基氨基烷基，氰基烷基，烷氧基羰基烷基，羧基烯基，烷氧基羰基，烷氧基烷基羰基，二烷基氨基羰基，二烷基氨基硫代羰基，苯氧基烷基羰基，哌啶子基烷基，吡啶羰基，取代或未取代的苯甲酰基或取代或未取代的苄基。 本发明的化合物可用作抗溃疡剂。

公开(公告)号：US5008282A

公开(公告)日：1991-04-16

申请号：US450264

申请日：1989-12-13

申请人： Tsuyoshi Tomiyama ,  Akira Tomiyama ,  Tadashi Shirai ,  Shuuichi Wakabayashi ,  Tomoyuki Kawai ,  Naoto Ueyama ,  Motoharu Sonegawa

发明人： Tsuyoshi Tomiyama ,  Akira Tomiyama ,  Tadashi Shirai ,  Shuuichi Wakabayashi ,  Tomoyuki Kawai ,  Naoto Ueyama ,  Motoharu Sonegawa

IPC分类号： C07D471/14 ,  C07D487/04 ,  C07D519/00

CPC分类号： C07D471/14 ,  C07D487/04

摘要： Derivatives of cyclic guanidine are disclosed, which are represented by the following formula:A--S--Rwherein A is ##STR1## R.sub.1 represent a lower alkyl or substituted phenyl or unsubstituted phenyl group; R.sub.2 is a lower alkyl; R.sub.3 is H or a lower alkyl; R is lower alkyl, alkenyl, alkynyl, alkanoyl, alkenoyl, dialkylaminoalkyl, cyanoalkyl, alkoxycarbonylalkyl, carboxylalkenyl, alkoxycarbonyl, alkoxyalkylcarbonyl, dialkylaminocarbonyl, dialkylaminothiocarbonyl, phenoxyalkylcarbonyl, piperidinoalkyl, pyridine carbonyl, substituted or unsubstituted benzoyl, or substituted or unsubstituted benzyl group.The compounds of the present invention are useful as anti-ulcerative agents.

摘要翻译： 公开了由下式表示的环状胍的衍生物：A-S-R，其中A为低级烷基或取代的苯基或未取代的苯基; R2是低级烷基; R3是H或低级烷基; R是低级烷基，烯基，炔基，烷酰基，烯酰基，二烷基氨基烷基，氰基烷基，烷氧基羰基烷基，羧基烯基，烷氧基羰基，烷氧基烷基羰基，二烷基氨基羰基，二烷基氨基硫代羰基，苯氧基烷基羰基，哌啶子基烷基，吡啶羰基，取代或未取代的苯甲酰基或取代或未取代的苄基。 本发明的化合物可用作抗溃疡剂。

公开(公告)号：US4002666A

公开(公告)日：1977-01-11

申请号：US516963

申请日：1974-10-22

申请人： Tadashi Shirai ,  Yasuhisa Tashiro ,  Shigeru Aoki

发明人： Tadashi Shirai ,  Yasuhisa Tashiro ,  Shigeru Aoki

IPC分类号： C07B57/00 ,  C07B31/00 ,  C07C19/00 ,  C07C67/00 ,  C07C227/00 ,  C07C227/20 ,  C07C227/34 ,  C07C229/36 ,  C07C231/00 ,  C07C231/12 ,  C07C231/20 ,  C07C233/47 ,  C07C103/46 ,  C07C103/84 ,  C07C125/06

CPC分类号： C07C271/06

摘要： Optically active p-hydroxyphenylglycine is prepared by reacting a racemic compound of a specified p-hydroxyphenylglycine derivative with optically active .alpha.-phenylethylamine to form a corresponding salt, obtaining two types of optically active salts therefrom by fractional crystallization, and obtaining optically active p-hydroxyphenylglycine by decomposition and hydrolysis of at least one of the optically active salts.

摘要翻译： 通过使特定的对羟基苯基甘氨酸衍生物的外消旋化合物与光学活性α-苯乙胺反应形成相应的盐，通过分级结晶获得两种类型的光学活性盐，得到光学活性对羟基苯基甘氨酸，制备光学活性对羟基苯基甘氨酸 通过至少一种光学活性盐的分解和水解。