公开(公告)号：US4035362A

公开(公告)日：1977-07-12

申请号：US672527

申请日：1976-03-31

申请人： Paolo Masi ,  Maurizio Foglio ,  Giovanni Franceschi ,  Antonino Suarato ,  Gianfranco Cainelli ,  Federico Arcamone

发明人： Paolo Masi ,  Maurizio Foglio ,  Giovanni Franceschi ,  Antonino Suarato ,  Gianfranco Cainelli ,  Federico Arcamone

IPC分类号： C07D205/08 ,  C07D205/095 ,  C07D501/08 ,  C07D501/10 ,  C07D501/20

CPC分类号： C07D501/08 ,  C07D205/095

摘要： A process for preparing cephalosporins of the structure: ##STR1## where R is any of hydrogen, C.sub.1 to C.sub.4 alkyl, t-butoxy, benzyloxy, cyano-methyl, thienyl-methyl, furyl-methyl, naphthyl-methyl, phenyl-methyl, phenoxy-methyl, phenoxy-isopropyl, pyridyl-4-thiomethyl and tetrazolyl-1-methyl;R.sub.1 is any of hydroxyl, C.sub.1 to C.sub.4 alkoxy, benzyloxy, p-methoxy- (or nitro-) benzyloxy, benzhydryloxy, triphenylmethoxy, phenacyloxy, p-halophenacyloxy and trichloroethoxy;Z is any of hydrogen, hydroxyl, --O--CO--C.sub.1 -C.sub.4 alkyl, --O--C.sub.1 -C.sub.4 alkyl, --Br, --I, --Cl, --N.sub.3, --NH.sub.2, --O--CO--CH.sub.3, --O--CO--NH.sub.2 and an -S-mononuclear nitrogen heterocyclic ring,By reacting compounds of the structure: ##STR2## IN WHICH R, R.sub.1, and Z are as above defined; R.sub.2 and R.sub.3 are the same or different and represent a C.sub.1 to C.sub.4 alkyl, a mononuclear aryl ring, --CN, a mononuclear heterocyclic ring or the radicals --COR.sub.4, COOR.sub.4, --PO(OR.sub.4).sub.2, --CO--NHR.sub.4 or R.sub.2 and R.sub.3 together may represent: ##STR3## where T represents >CH.sub.2, -N--R.sub.4 ; and R.sub.4 is lower alkyl, a mononuclear aryl ring or a mononuclear heterocyclic ring,Alone or as mixtures with each other in a suitable solvent at a temperature between -100 and +120.degree. C with a strong base to give compounds of formula I that are a mixture of .DELTA..sub.2 and .DELTA..sub.3 cephem-derivatives from which the .DELTA..sub.3 cephem derivatives can be obtained.

摘要翻译： 一种制备结构式头孢菌素的方法：其中R是氢，C1-C4烷基，叔丁氧基，苄氧基，氰基 - 甲基，噻吩基 - 甲基，呋喃基 - 甲基，萘基 - 甲基，苯基 - 甲基 ，苯氧基甲基，苯氧基 - 异丙基，吡啶基-4-硫代甲基和四唑基-1-甲基; R1是羟基，C1〜C4烷氧基，苄氧基，对甲氧基 - （或硝基）苄氧基，二苯甲氧基，三苯基甲氧基，苯甲酰氧基，对卤代苯氧基和三氯乙氧基中的任一个。 Z是氢，羟基，-O-CO-C 1 -C 4烷基，-O-C 1 -C 4烷基，-Br，-I，-Cl，-N 3，-NH 2，-O-CO-CH 3，-O -CO-NH 2和-S-单核氮杂环，通过反应结构的化合物：其中R，R 1和Z如上所定义;其中R，R 1和Z如上所定义; R2和R3相同或不同，表示C1至C4烷基，单核芳基环，-CN，单核杂环或基团-COR4，COOR4，-PO（OR4）2，-CO-NHR4或R2和 R3一起可以表示：其中T表示> CH 2，-N-R 4; 并且R 4为低级烷基，单核芳基环或单核杂环，单独或混合于适宜溶剂中的温度为-100℃和+120℃之间的强碱，得到式I化合物 可以获得DELTA 2和DELTA 3头孢烯衍生物的混合物，其中可以获得DELTA 3头孢烯衍生物。

公开(公告)号：US4143037A

公开(公告)日：1979-03-06

申请号：US797608

申请日：1977-05-16

申请人： Maurizio Foglio ,  Giovanni Franceschi ,  Paolo Masi ,  Antonino Suarato

发明人： Maurizio Foglio ,  Giovanni Franceschi ,  Paolo Masi ,  Antonino Suarato

IPC分类号： C07D205/095 ,  C07D205/08

CPC分类号： C07D205/095

摘要： A process is disclosed for preparing compounds of structure: ##STR1## where R.sup.1 is hydroxyl, alkoxy with 1 to 4 carbon atoms, trichloroethoxy, benzyloxy, p-methoxybenzyloxy, p-nitrobenzyloxy, benzhydryloxy, triphenylmethoxy, phenacyloxy, or p-halophenacyloxy;Z is hydrogen, hydroxyl, --O-alkyl, --O--CO-alkyl, --Br, --I, --N.sub.3, --O--CO--CH.sub.3, O--CO--NH.sub.2, or an S-mononuclear heterocyclic ring,Starting from ##STR2## where R is hydrogen, alkyl having from 1 to 4 carbon atoms, cyano-methyl, thienyl-methyl, furyl-methyl, naphthyl-methyl, phenyl-methyl, phenoxy-methyl, phenyl-isopropyl, phenoxy-isopropyl, pyridyl-4-thiomethyl, or tetrazolyl-1-methyl;R.sup.2 and R.sup.3 are lower alkyl, a mononuclear aryl ring, CN, a mononuclear heterocyclic ring or the radicals --COR.sup.4, --COOR.sup.4, ##STR3## --CONHR.sup.4, or R.sub.2 and R.sub.3 together represent ##STR4## where T represents ##STR5## and R.sup.4 is a lower alkyl, a mononuclear aryl or heterocyclic ring, WHEREIN THE COMPOUND (II') is reacted with a phosphorous halide in the presence of a tertiary amine, the corresponding imino chloride is reacted with a lower aliphatic alcohol, the iminoether so formed is hydrolyzed in an acid medium, and the resultant 3-amino-2-.beta.-thiohydrazoazetidinone: ##STR6## in which R.sup.1, R.sup.2, R.sup.3 and Z have the meanings given heretofore,Is reacted between -100.degree. and +120.degree. C. with inorganic basic or weakly acid oxides or inorganic and organic bases, to give (V).

公开(公告)号：US4155911A

公开(公告)日：1979-05-22

申请号：US820895

申请日：1977-08-01

申请人： Maurizio Foglio ,  Antonino Suarato ,  Paolo Masi ,  Giovanni Franceschi ,  Giorgio Palamidessi ,  Luigi Bernardi

发明人： Maurizio Foglio ,  Antonino Suarato ,  Paolo Masi ,  Giovanni Franceschi ,  Giorgio Palamidessi ,  Luigi Bernardi

IPC分类号： C07D205/08 ,  C07D513/04

CPC分类号： C07D513/04 ,  C07D205/08

摘要： A new process is disclosed for the preparation of compounds of structure: ##STR1## and are as defined herein characterized in that a compound of structure ##STR2## where R and R.sup.1 have the meanings given herein, is reacted in a suitable solvent with a haloamide in the presence of a metal oxide or a haloamide in the presence of a free radical initiator under the influence of light or heat or alternatively with a halogen in the presence of a metal oxide, to give a compound of structure: ##STR3## where R and R.sup.1 have the meanings given herein, Hal is a halogen atom; THE INTERMEDIATE COMPOUND (III) in a suitable solvent is then reacted with an appropriate nucleophilic reagent to obtain the compound IV where Z replaces Hal, where Z is defined herein;The compound (IV) is then subjected to an allylic halogenation in a suitable solvent by reacting it with a haloamide either under the influence of light alone or by heating it in the presence of a free radical initiator, to give a compound of structure: ##STR4## where R, R.sup.1 and Hal and Z have the above meanings; THE INTERMEDIATE COMPOUND (V) is then reacted with a reducing agent to give finally the desired compound (I).

摘要翻译： 公开了用于制备结构式（I）的化合物的新方法，其定义如下，其特征在于其中R和R 1具有本文给出的含义的结构式（II）的化合物在 在金属氧化物或卤代酰胺的存在下，在自由基引发剂的存在下，在光或热的作用下，或者在卤素存在下，在金属氧化物的存在下，与卤代酰胺合适的溶剂，得到结构化合物 （III）其中R和R1具有本文给出的含义，Hal是卤素原子; 然后将合适的溶剂中的中间体化合物（III）与合适的亲核试剂反应，得到Z代替Hal的化合物IV，其中Z在本文中定义; 然后使化合物（IV）在合适的溶剂中通过与单独的光的影响下的卤代酰胺反应或通过在自由基引发剂的存在下加热使其与卤代酰胺反应，得到结构式 （V）其中R，R1，Hal和Z具有上述含义; 然后将中间体化合物（V）与还原剂反应，最终得到所需化合物（I）。

公开(公告)号：US4012381A

公开(公告)日：1977-03-15

申请号：US586376

申请日：1975-06-12

申请人： Maurizio Foglio ,  Giovanni Franceschi ,  Paolo Masi ,  Antonino Suarato

发明人： Maurizio Foglio ,  Giovanni Franceschi ,  Paolo Masi ,  Antonino Suarato

IPC分类号： C07D205/095 ,  C07D501/08 ,  C07D501/18 ,  C07D501/20

CPC分类号： C07D205/095

摘要： A process is disclosed for preparing derivatives of 7-amino-cephalosporanic acid and 7-amino-desacetoxycephalosporanic acid of structure: starting from a 3-acylamino-2.beta.-thiohydrazoazetidinone of structure: ##STR1## wherein the compound (II') is reacted with a phosphorous halide in the presence of a tertiary amine, the corresponding imino chloride is reacted with a lower aliphatic alcohol, the iminoether so formed is hydrolyzed with water in an acid medium, and the resultant 3-amino-2.beta.-thiohydrazoazetidinone of structure: ##STR2## is reacted in a suitable solvent and at a temperature between -100.degree. and +120.degree. C with a compound selected from the class consisting of inorganic basic or weakly acid oxides and inorganic and organic bases, to finally give the desired compound (V) which is isolated and purified in known manner.2.beta.-thiohydrazoazetidinones are also disclosed as intermediates.

摘要翻译： 公开了一种制备以下结构的3-氨基 - 头孢烷酸和7-氨基 - 脱乙酰氧基头孢烷酸的衍生物的方法，其结构如下：起始于结构如下的3-酰基氨基-2β-硫代代氮杂环丁酮：（II' ），其中化合物（II'）在叔胺存在下与卤化磷反应，相应的亚氨基氯与低级脂族醇反应，所形成的亚氨基醚在酸性介质中用水水解，得到的 将结构如下的3-氨基-2β-硫代代代氮杂环丁酮在合适的溶剂中，在-100至+ 120℃的温度下与选自无机碱性或弱碱性的化合物反应 酸性氧化物和无机和有机碱，最终得到所需的化合物（V），其以已知方式分离和纯化。

公开(公告)号：US4077970A

公开(公告)日：1978-03-07

申请号：US603605

申请日：1975-08-11

申请人： Maurizio Foglio ,  Antonino Suarato ,  Paolo Masi ,  Giovanni Franceschi ,  Giorgio Palamidessi ,  Luigi Bernardi

发明人： Maurizio Foglio ,  Antonino Suarato ,  Paolo Masi ,  Giovanni Franceschi ,  Giorgio Palamidessi ,  Luigi Bernardi

IPC分类号： C07D205/08 ,  C07D513/04 ,  C07D513/08

CPC分类号： C07D513/04 ,  C07D205/08

摘要： A process is disclosed for the preparation of a compound of the formula ##STR1## where R and R.sup.1 are defined herein below, wherein a compound of the structure; ##STR2## is reacted in a suitable solvent with a haloamide in the presence of a metal oxide or a haloamide in the presence of a free radical initiator under the influence of light or heat or alternatively with a halogen in the presence of a metal oxide, to give a compound of the structure; ##STR3## which compound, in a suitable solvent is reacted with a suitable nucleophilic reagent to obtain the compound; ##STR4## which compound is then subjected to allylic halogenation to give a compound of the structure; ##STR5## which is then reacted with a reducing agent to yield I.

摘要翻译： 公开了用于制备下式化合物的方法，其中R和R 1如下文所定义，其中该结构的化合物; 在自由基引发剂的存在下，在光或热的作用下，或者在卤素存在下，在金属氧化物或卤代酰胺的存在下，在合适的溶剂中与卤代酰胺反应。 ，得到结构的化合物; 该化合物在合适的溶剂中与合适的亲核试剂反应得到化合物; 然后将该化合物进行烯丙基卤化，得到结构的化合物; 然后将其与还原剂反应以产生I.

公开(公告)号：US4067866A

公开(公告)日：1978-01-10

申请号：US700972

申请日：1976-06-29

申请人： Maurizio Foglio ,  Giovanni Franceschi ,  Paolo Masi ,  Antonino Suarato

发明人： Maurizio Foglio ,  Giovanni Franceschi ,  Paolo Masi ,  Antonino Suarato

IPC分类号： C07D501/08 ,  C07F9/24 ,  C07D205/08 ,  C07D409/12

CPC分类号： C07F9/2458

摘要： A process is disclosed for preparing cephalosporins of structure: ##STR1##where R is selected from the class consisting of hydrogen, alkyl having from 1 to 4 carbon atoms, cyano-methyl-, thienyl-methyl, furyl-methyl-, naphthyl-methyl-, phenyl-methyl-, phenoxy-methyl-, phenyl-isopropyl-, phenoxy-isopropyl-, pyridyl-4-thiomethyl-, and tetrazolyl-1-methyl;R.sup.1 is selected from the class consisting of hydroxyl, alkoxy with 1 to 4 carbon atoms, trichloroethoxy-, benzyloxy-, p-methoxy-benzyloxy-, p-nitrobenzyloxy-, benzhydryloxy-, triphenylmethoxy-, phenacyloxy-, and p-halophenacyloxy;Z is selected from the class consisting of hydrogen, hydroxyl, --O--alkyl, --O--CO--alkyl, --Br, --I, --N.sub.3, --NH.sub.2, --O--CO--CH.sub.3, --O--CO--NH.sub.2 and an --S--mononuclear nitrogen heterocyclic ring;Wherein a compound of structure: ##STR2## is reacted in a suitable solvent at a temperature between -20.degree. C and +80.degree. C, in the presence of an aqueous organic or inorganic acid with an azoderivative of the formula: ##STR3## where R.sup.2 and R.sup.3 are equal or different and represent lower alkyl, a mononuclear aryl ring, CN--, a mononuclear heterocyclic ring, or the radicals --COR.sup.4, --COOR.sup.4, ##STR4## --CONHR.sup.4, or R.sub.2 and R.sub.3 together may represent the residues; ##STR5## where T represents >CH.sub.2, >N -- R.sup.4, and R.sup.4 is lower alkyl, a mononuclear aryl ring or a mononuclear heterocyclic, ring to give a compound of structure: ##STR6## in which R, R.sup.1, R.sup.2, R.sup.3, and Z have the meanings given above, and said intermediate (II') is reacted in a suitable solvent at a temperature between -100.degree. C and +120.degree. C with a compound selected from the class consisting of inorganic basic or weakly acid oxides, and inorganic and organic bases, to finally give the desired compound (III) which is isolated and purified in known manner.

公开(公告)号：US4018776A

公开(公告)日：1977-04-19

申请号：US601586

申请日：1975-08-04

申请人： Maurizio Foglio ,  Paolo Masi ,  Antonino Suarato ,  Giovanni Franceschi

发明人： Maurizio Foglio ,  Paolo Masi ,  Antonino Suarato ,  Giovanni Franceschi

IPC分类号： A61K31/545 ,  C07D20060101 ,  C07D501/04 ,  C07D501/06 ,  C07D501/08 ,  C07D501/10 ,  C07D501/14 ,  C07D501/16 ,  C07D501/20 ,  C07D501/22 ,  C07D501/24 ,  C07D501/28 ,  C07D501/30 ,  C07D501/32 ,  C07D501/34 ,  C07D501/36 ,  C07D501/40 ,  C07D501/42 ,  C07D501/44 ,  C07D501/46 ,  C07D501/60 ,  C07D513/04

CPC分类号： C07D501/08

摘要： A process is disclosed for preparing a cephalosporin of structure: ##STR1## where R is selected from the class consisting of hydrogen, alkyl having from 1 to 4 carbon atoms, cyano-methyl, thienyl-methyl, furyl-methyl, naphthyl-methyl, phenyl-methyl, phenoxy-methyl, phenyl-isopropyl, phenoxy-isopropyl, pyridyl-4-thiomethyl, tetrazolyl-1-methyl;R.sup.1 is selected from the class consisting of hydroxy, alkoxy having from 1 to 4 carbon atoms, trichloroethoxy, benzyloxy, p-methoxy-benzyloxy, p-nitrobenzyloxy, benzhydryloxy, triphenylmethoxy, phenacyloxy, p-halophenacyloxy; andZ is selected from the class consisting of hydrogen, hydroxy, --O--Alkyl, --O--CO--Alkyl, --Br, --I, --NH.sub.2, --O--COCH.sub.3, --O--CO--NH.sub.2, and an --S-mononuclear nitrogen heterocyclic ring,Wherein a compound of structure: ##STR2## where R, R.sup.1 and Z have the above meanings, is reacted with iodine in a suitable aqueous solvent at a temperature between 5.degree. and 80.degree. C in the presence of an oxide of a heavy metal or with a free radical initiator under the influence of light or heat, to give a compound of structure: ##STR3## in which R, R.sup.1 and Z have the above meanings, AND THE SAID INTERMEDIATE (II) is reacted in a suitable solvent with a compound selected from the class consisting of inorganic and organic bases to finally give the desired compound (III) which is then isolated and purified in per se known manner.

摘要翻译： 公开了一种制备头孢菌素的方法，其结构如下：其中R选自氢，具有1至4个碳原子的烷基，氰基 - 甲基，噻吩基 - 甲基，呋喃基 - 甲基，萘基 - 甲基，苯基 - 甲基，苯氧基 - 甲基，苯基 - 异丙基，苯氧基 - 异丙基，吡啶基-4-硫代甲基，四唑基-1-甲基; R1选自羟基，具有1至4个碳原子的烷氧基，三氯乙氧基，苄氧基，对甲氧基 - 苄氧基，对硝基苄氧基，二苯甲氧基，三苯甲氧基，苯甲酰氧基，对卤代苯甲酰氧基; 并且Z选自氢，羟基，-O-烷基，-O-CO-烷基，-Br，-I，-NH2，-O-COCH3，-O-CO-NH2和-S - 单核氮杂环，其中R，R 1和Z具有上述含义的化合物：其中R，R 1和Z具有上述含义，在合适的水性溶剂中，在5℃至80℃的温度下， 重金属的氧化物或在光或热的影响下的自由基引发剂，得到结构式为的化合物：其中R，R 1和Z具有上述含义，并且所述中间体（II） ）在合适的溶剂中与选自无机和有机碱的化合物反应，最终得到所需的化合物（III），然后以本身已知的方式分离和纯化。

公开(公告)号：US4191755A

公开(公告)日：1980-03-04

申请号：US901358

申请日：1978-05-01

申请人： Paolo Masi ,  Antonino Suarato ,  Luigi Bernardi ,  Federico Arcamone

发明人： Paolo Masi ,  Antonino Suarato ,  Luigi Bernardi ,  Federico Arcamone

IPC分类号： C07C50/38 ,  A61K31/65 ,  A61P31/04 ,  A61P35/00 ,  C07C45/00 ,  C07C67/00 ,  C07H15/252 ,  A61K31/71 ,  C07H15/24

CPC分类号： C07H15/252 ,  Y10S514/908

摘要： Daunomycin derivatives of the formula: ##STR1## wherein R.sub.1 is a lower alkyl having from 1 to 4 carbon atoms and R is hydrogen or a trifluoroacetyl group are useful in treating certain mammalian tumors.

摘要翻译： 下式的道诺霉素衍生物：其中R1是具有1至4个碳原子的低级烷基，R是氢或三氟乙酰基可用于治疗某些哺乳动物肿瘤。

公开(公告)号：US4188377A

公开(公告)日：1980-02-12

申请号：US872626

申请日：1978-01-26

申请人： Antonino Suarato ,  Paolo Masi ,  Luigi Bernardi ,  Federico Arcamone

发明人： Antonino Suarato ,  Paolo Masi ,  Luigi Bernardi ,  Federico Arcamone

IPC分类号： C07H15/252 ,  A61K31/70 ,  C07H15/24

CPC分类号： C07H15/252 ,  Y10S514/908

摘要： N-acyl derivatives of the known antitumor antibiotic carminomycin, particularly N-trifluoroacetyl carminomycin, have a much lower toxicity than carminomycin.

摘要翻译： 已知抗肿瘤抗生素卡明霉素的N-酰基衍生物，特别是N-三氟乙酰卡明霉素，毒性低于卡培霉素。

公开(公告)号：US4134903A

公开(公告)日：1979-01-16

申请号：US887782

申请日：1978-03-17

申请人： Paolo Masi ,  Antonino Suarato ,  Pietro Giardino ,  Luigi Bernardi ,  Federico Arcamone

发明人： Paolo Masi ,  Antonino Suarato ,  Pietro Giardino ,  Luigi Bernardi ,  Federico Arcamone

IPC分类号： C07H15/252 ,  C07C49/72 ,  C07C49/73 ,  C07C97/26 ,  C09B1/30

CPC分类号： C07H15/252

摘要： Aglycones of the formula ##STR1## and Toslyhydrazones of the formula ##STR2## wherein R.sub.1, R.sub.2 and Ts have meanings described in the specification, and process for preparing a compound of formula (V).

摘要翻译： 式（Ⅹ）的Ag con））of of hyd hyd V V V V））））））V V V V V V V V V V V V V V V V V V V V V V V V V V V V V V V V V V V V ）。