Synthetic routes to azetidinones related to nocardicin
    1.
    发明授权
    Synthetic routes to azetidinones related to nocardicin 失效
    与诺卡氏菌有关的氮杂环丁酮的合成途径

    公开(公告)号:US4230619A

    公开(公告)日:1980-10-28

    申请号:US921070

    申请日:1978-06-30

    摘要: There is disclosed a process for the manufacture of azetidinones related to nocardicin having the formula ##STR1## wherein R is a saturated or unsaturated alkyl having from 1 to 6 carbon atoms, .alpha.-aminobenzyl, benzyl, free or substituted phenyl, or a free or substituted heterocyclic;R.sub.1 is hydrogen, alkyl having from 1 to 4 carbon atoms, trimethylsilyl, trichloroethyl, benzhydryl or benzyl; andR.sub.2 is a free or substituted phenyl, or a free or substituted heterocyclic, using the same starting compound, but with the possibility of proceeding to the final compound via two somewhat different routes. A number of novel intermediates are also disclosed.

    摘要翻译: 公开了制备与具有式(I)的式(I)的诺卡品相关的氮杂环丁酮的方法,其中R是具有1至6个碳原子的饱和或不饱和烷基,α-氨基苄基,苄基,游离或取代的苯基,或 游离或取代杂环; R1是氢,具有1至4个碳原子的烷基,三甲基甲硅烷基,三氯乙基,二苯甲基或苄基; 并且R2是游离的或取代的苯基,或游离的或取代的杂环,使用相同的起始化合物,但是有可能通过两个有些不同的途径进入最终的化合物。 还公开了许多新颖的中间体。

    7-Oxo-4-1-aza-bicyclo-[3,2,0]-heptane derivatives
    2.
    发明授权
    7-Oxo-4-1-aza-bicyclo-[3,2,0]-heptane derivatives 失效
    7-氧代-4-氮杂 - 双环 - [3,2,0] - 庚烷衍生物

    公开(公告)号:US4331677A

    公开(公告)日:1982-05-25

    申请号:US95790

    申请日:1979-11-19

    摘要: This invention relates to 7-oxo-4-thia-1-aza-bicyclo-[3,2,0]-heptane derivatives, to processes for their synthesis from esters of penicillanic acid 1-oxide, and to intermediate compounds obtained in the synthesis.More particularly, the present invention relates to new and novel compounds of formula (1): ##STR1## wherein R is a hydrogen atom, an alkyl having from 1 to 5 carbon atoms, trichloroethyl, benzyl, p-nitrobenzyl, diphenylmethyl, acetoxymethyl, pivaloyloxymethyl, phthalidyl, trimethylsilyl or a group of formula ##STR2## and R.sup.1 is --CH.sub.2 OH, --CH.sub.2 OCOR.sup.2, --CH.sub.2 OR.sup.3, --COOR.sup.2, --CHO, --CH.sub.2 SH, --CH.sub.2 SR.sup.4, --CH.sub.2 NH.sub.2, --CH.sub.2 NHCOR.sup.2 in which R.sup.2 is an alkyl having from 1 to 5 carbon atoms, aryl, aralkyl or a five- or six-membered heterocyclic ring containing one or more heteroatoms; R.sup.3 is an alkyl having from 1 to 5 carbon atoms, benzyl, trityl, trialkylsilyl; and R.sup.4 is a five- or six-membered heterocyclic ring containing one or more heteroatoms, benzyl, trityl or trialkylsilyl;and to the synthesis of such compounds.Compounds of formula (1) (E+Z isomers) are endowed with antibacterial activity.

    摘要翻译: 本发明涉及7-氧代-4-硫杂-1-氮杂 - 双环[3,2,0] - 庚烷衍生物,用于由青霉酸1-氧化物的酯合成的方法,以及在 合成。 更具体地说,本发明涉及新的和新的式(1)化合物:其中R是氢原子,具有1至5个碳原子的烷基,三氯乙基,苄基,对硝基苄基,二苯基甲基 ,乙酰氧基甲基,新戊酰氧基甲基,邻苯二甲酰基,三甲基甲硅烷基或式的基团,并且R 1是-CH 2 OH,-CH 2 OCOR 2,-CH 2 OR 3,-COOR 2,-CHO,-CH 2 SH,-CH 2 SR 4,-CH 2 NH 2,-CH 2 NHCOR 2,其中R 2是 具有1至5个碳原子的烷基,芳基,芳烷基或含有一个或多个杂原子的五元或六元杂环; R3是具有1至5个碳原子的烷基,苄基,三苯甲基,三烷基甲硅烷基; 并且R 4是含有一个或多个杂原子的五元或六元杂环,苄基,三苯甲基或三烷基甲硅烷基; 以及这些化合物的合成。 式(1)化合物(E + Z异构体)具有抗菌活性。

    .beta.-Lactam-containing antibacterial agents and .beta.-lactamase
inhibitors
    3.
    发明授权
    .beta.-Lactam-containing antibacterial agents and .beta.-lactamase inhibitors 失效
    含β-内酰胺的抗菌剂和β-内酰胺酶抑制剂

    公开(公告)号:US4558042A

    公开(公告)日:1985-12-10

    申请号:US595336

    申请日:1984-03-30

    CPC分类号: C07D499/88

    摘要: There are disclosed .beta.-lactam-containing compounds of the formula: ##STR1## where R is hydrogen, lower alkyl, trichloroethyl, acetonyl, benzyl, substituted benzyl, phenyl, substituted phenyl, benzidryl or a residue that will undergo metabolic activation "in vivo" and have favorable pharmacokinetic properties; R.sup.1 is a hydrogen atom, lower alkyl, lower alkoxy, cycloalkyl, or hydroxyalkyl, with the alcoholic function of the hydroxyalkyl being free or protected; Z is hydrogen, halogen, hydroxy, amino, carbamoyloxy, mercapto, pyridinium, OR.sup.2, OCOR.sup.2, NHCOR.sup.2, or SR.sup.3 wherein each of R.sup.2 and R.sup.3 is any of lower alkyl, aryl, or a heterocyclic ring, each of which may be substituted or unsubstituted, and n is 0 or 1. The compounds have broad spectrum antibacterial activity and .beta.-lactamase inhibiting activity. Processes for the production of the .beta.-lactam-containing compounds and various intermediates in the production of those compounds are also disclosed.

    摘要翻译: 公开了含有β-内酰胺的化合物,其中R为氢,低级烷基,三氯乙基,丙酰基,苄基,取代的苄基,苯基,取代的苯基,苯并或将经历代谢活化的残基。 “并具有有利的药代动力学性质; R1是氢原子,低级烷基,低级烷氧基,环烷基或羟基烷基,其羟基烷基的醇官能团是游离或保护的; Z是氢,卤素,羟基,氨基,氨基甲酰氧基,巯基,吡啶鎓,OR2,OCOR2,NHCOR2或SR3,其中R2和R3各自为低级烷基,芳基或杂环, 未取代的,n为0或1.该化合物具有广谱抗菌活性和β-内酰胺酶抑制活性。 还公开了用于生产含有β-内酰胺的化合物和这些化合物生产中的各种中间体的方法。

    .beta.-Lactam-containing antibacterial agents and .beta.-lactamase
inhibitors
    4.
    发明授权
    .beta.-Lactam-containing antibacterial agents and .beta.-lactamase inhibitors 失效
    含β-内酰胺的抗菌剂和β-内酰胺酶抑制剂

    公开(公告)号:US4482565A

    公开(公告)日:1984-11-13

    申请号:US261247

    申请日:1981-05-06

    CPC分类号: C07D499/88

    摘要: There are disclosed .beta.-lactam-containing compounds of the formula: ##STR1## where R is hydrogen, lower alkyl, trichloroethyl, acetonyl, benzyl, substituted benzyl, phenyl, substituted phenyl, benzidryl or a residue that will undergo metabolic activation "in vivo" and have favorable pharmacokinetic properties; R.sup.1 is a hydrogen atom, lower alkyl, lower alkoxy, cycloalkyl, or hydroxyalkyl, with the alcoholic function of the hydroxyalkyl being free or protected; Z is hydrogen, halogen, hydroxy, amino, carbamoyloxy, mercapto, pyridinium, OR.sup.2, OCOR.sup.2, NHCOR.sup.2, or SR.sup.3 wherein each of R.sup.2 and R.sup.3 is any of lower alkyl, aryl, or a heterocyclic ring, each of which may be substituted or unsubstituted, and n is 0 or 1. The compounds have broad spectrum antibacterial activity and .beta.-lactamase inhibiting activity. Processes for the production of the .beta.-lactam-containing compounds and various intermediates in the production of those compounds are also disclosed.

    摘要翻译: 公开了含有β-内酰胺的化合物,其中R为氢,低级烷基,三氯乙基,丙酰基,苄基,取代的苄基,苯基,取代的苯基,苯并或将经历代谢活化的残基。 “并具有有利的药代动力学性质; R1是氢原子,低级烷基,低级烷氧基,环烷基或羟基烷基,其羟基烷基的醇官能团是游离或保护的; Z是氢,卤素,羟基,氨基,氨基甲酰氧基,巯基,吡啶鎓,OR2,OCOR2,NHCOR2或SR3,其中R2和R3各自为低级烷基,芳基或杂环, 未取代的,n为0或1.该化合物具有广谱抗菌活性和β-内酰胺酶抑制活性。 还公开了用于生产含有β-内酰胺的化合物和这些化合物生产中的各种中间体的方法。

    Methods for preparing cephalosporins
    6.
    发明授权
    Methods for preparing cephalosporins 失效
    头孢菌素的制备方法

    公开(公告)号:US4035362A

    公开(公告)日:1977-07-12

    申请号:US672527

    申请日:1976-03-31

    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。

    Total synthesis of 7-oxo-4-thia-1-azabicyclo-[3,2,0]-heptane-2-carboxyl
derivatives useful as .beta.-lactamase inhibitors and antibacterial
agents
    7.
    发明授权
    Total synthesis of 7-oxo-4-thia-1-azabicyclo-[3,2,0]-heptane-2-carboxyl derivatives useful as .beta.-lactamase inhibitors and antibacterial agents 失效
    可用作β-内酰胺酶抑制剂和抗菌剂的7-氧代-4-硫杂-1-氮杂双环[3,2,0] - 庚烷-2-羧基衍生物的全合成

    公开(公告)号:US4269771A

    公开(公告)日:1981-05-26

    申请号:US93603

    申请日:1979-11-13

    摘要: A process is disclosed for the preparation of compounds of formula I: ##STR1## wherein R is hydrogen, lower alkyl, trichloroethyl, benzyl, p-nitrobenzyl, acetoxymethyl, pivaloyloxymethyl, phthalidyl, or a --CH(CH.sub.3)OCOOEt group;R.sup.1 is --CH.sub.2 OH, --CHO, --CH.sub.2 SH, --CH.sub.2 NH.sub.2, --CH.sub.2 OCOR.sup.2, --COOR.sup.2, --CH.sub.2 NHCOR.sup.2, --CH.sub.2 OR.sup.3, or --CH.sub.2 SR.sup.4 where R.sup.2 is a lower alkyl, aryl or a heterocyclic ring, R.sup.3 is a lower alkyl, benzyl, or trityl, and R.sup.4 is a five- or six-member heterocyclic ring containing one or more heteroatoms,which comprises reacting a 4-acetoxy azetidinone with a .beta.-thioketoester to form a mixture, reacting said mixture with thionyl chloride followed by reaction with a phosphine and a base, ozonolyzing and heating to obtain the compounds of formula I.

    摘要翻译: 公开了制备式I化合物的方法:其中R是氢,低级烷基,三氯乙基,苄基,对硝基苄基,乙酰氧基甲基,新戊酰氧基甲基,邻苯二甲酰基或-CH(CH 3)OCOOEt基团; R1是-CH2OH,-CHO,-CH2SH,-CH2NH2,-CH2OCOR2,-COOR2,-CH2NHCOR2,-CH2OR3或-CH2SR4,其中R2是低级烷基,芳基或杂环,R3是低级烷基,苄基, 或三苯甲基,R4是含有一个或多个杂原子的五元或六元杂环,其包括使4-乙酰氧基氮杂环丁酮与β-硫代酮反应形成混合物,使所述混合物与亚硫酰氯反应,然后与 膦和碱,进行臭氧分解和加热,得到式I化合物。

    3,7-Disubstituted cephalosporins
    9.
    发明授权
    3,7-Disubstituted cephalosporins 失效
    3,7-二取代头孢菌素

    公开(公告)号:US4148996A

    公开(公告)日:1979-04-10

    申请号:US797606

    申请日:1977-05-16

    CPC分类号: C07D501/36 A61K31/545

    摘要: 7-Acylamino-3-pyrazinylthiomethyl-3-cephem-4-carboxylic acids are disclosed having the general formula: ##STR1## wherein R is an alkyl having from 1 to 5 carbon atoms or ##STR2## wherein Y = Y.sup.1 = HY = y.sup.1 = clY = cl, Y.sup.1 = FY = h,y .sup.1 = cl andIn which n is an integer from 1 to 4, X is O or S, and R.sub.2 is thienyl, phenyl, 1,4-cyclohexadienyl, phenoxy, pyrazinyl and substituted phenyl, thienyl, pyrazinyl and phenoxy, the substituent being selected from the group consisting of hydroxy, chlorine, bromine, and alkyl and alkoxy having from 1 to 4 carbon atoms;R.sub.3 is alkali metal such as sodium or potassium, hydrogen, alkyl having from 1 to 4 carbon atoms, benzyl, trichloroethyl, methoxybenzyl, benzhydryl, pivaloyloxymethyl, and an alkaline earth metal; R.sup.1 may be a pyrazinyl of the general formulae: ##STR3## in which R.sup.4, R.sup.5, R.sup.6 are equal or different and are selected from the group consisting of F, Cl, Br, hydrogen, alkyl, phenyl, cyano, thiocyano, carboxyl, carboxyalkyl, carboxamido, thiocarboxamido, hydroxy, alkoxy, thiol, alkylthio, amino, alkylamino, phenylamino. By the terms alkyl, an alkyl having from 1 to 4 carbon atoms is intended. Processes for making them are also disclosed.The new cephalosporin derivatives of formula (I) exhibit a broad spectrum antibacterial activity and are useful as therapeutic agents in the treatment of infectious diseases caused by gram-negative and gram-positive bacteria.

    摘要翻译: 公开了具有以下通式的7-酰基氨基-3-吡嗪基硫甲基-3-头孢烯-4-羧酸:其中R是具有1至5个碳原子的烷基或者具有1或5个碳原子的烷基 其中Y = Y1 = HY = Y1 = C1 Y = C1,Y1 = FY = H,Y1 = C1和IN,其中N为1至4的整数,X为O或S,R2为噻吩基, 苯基,1,4-环己二烯基,苯氧基,吡嗪基和取代的苯基,噻吩基,吡嗪基和苯氧基,所述取代基选自羟基,氯,溴以及具有1至4个碳原子的烷基和烷氧基; R3是碱金属如钠或钾,氢,具有1至4个碳原子的烷基,苄基,三氯乙基,甲氧基苄基,二苯甲基,新戊酰氧基甲基和碱土金属; R 1可以是以下通式的吡嗪基:其中R 4,R 5,R 6相同或不同,并且选自F,Cl,Br,氢,烷基,苯基,氰基,硫氰基,羧基, 羧基烷基,甲酰氨基,硫代甲酰胺基,羟基,烷氧基,硫醇,烷硫基,氨基,烷基氨基,苯基氨基。 术语烷基是指具有1至4个碳原子的烷基。 还披露了制作它们的过程。

    Paromomycin containing compounds and method of use
    10.
    发明授权
    Paromomycin containing compounds and method of use 失效
    含有溴霉素的化合物及其使用方法

    公开(公告)号:US4337248A

    公开(公告)日:1982-06-29

    申请号:US156478

    申请日:1980-06-04

    CPC分类号: C07H15/232

    摘要: Compounds are disclosed of the formula ##STR1## wherein R.sub.1 represents a hydrogen or chlorine atom, as well as intermediates. These include 4'-deoxy-paromomycin; 4'-deoxy-4'-epi-chloro-paromomycin; 4'-deoxy-4'-epi-chloro-penta-N-benzyloxycarbonylparomomycin; 4'-deoxy-penta-N-benzyloxycarbonylparomomycin; 6,3',2",5",3"',4"'-hexa-O-acetyl-6'-O-benzoyl-4'-deoxy-penta-N-benzyloxycarbonylparomomycin; 6,3',2",5",3"',4"'-hexa-O-acetyl-6'-O-benzoyl-4'-epi-chloro-4'-deoxy-penta-N-benzyloxycarbonylparomomycin; 6,3',2",5",3"',4"'-hexa-O-acetyl-6'-O-benzyl-penta-N-benzyloxycarbonylparomomycin; 6,3',2",5",3"',4"'-hexa-O-acetyl-6'-O-benzoyl-4'-O-[(methylthio)-thiocarbonyl]-penta-N-benzyloxycarbonylparomomycin; and 6,3',2",5",3"',4"'-hexa-O-acetyl-6'-O-benzoyl-4'-O-[(phenylthio)-thiocarbonyl]-penta-N-benzyloxycarbonylparomomycin. The compounds illustrated by the structural formula are useful in treating amoebic dysentery in man and animals.

    摘要翻译: 公开了下式的化合物:其中R 1表示氢或氯原子,以及中间体。 这些包括4'-脱氧巴马霉素; 4'-脱氧-4'-表 - 氯 - 巴龙霉素; 4'-脱氧-4'-表 - 氯 - 五-N-苄氧羰基巴霉素; 4'-脱氧 - 五-N-苄氧羰基巴霉素; 6,3',2“,5”,3“,4”' - 六-O-乙酰基-6'-O-苯甲酰基-4'-脱氧-5-N-苄氧基羰基巴霉素; 6,3',2“,5”,3“,4” - 六-O-乙酰基-6'-O-苯甲酰基-4'-表氯 - 4'-脱甲基 - 五 -N-苄氧羰基巴霉素; 6,3',2“,5”,3“,4”' - 六-O-乙酰基-6'-O-苄基 - 五-N-苄氧基氨基辛基巴霉素; 6,3',2“,5”,3“,4” - 六-O-乙酰基-6'-O-苯甲酰基-4'-O - [(甲硫基) - 噻吩基] 五-N-苄氧羰基巴霉素; 和6,3',2“,5”,3“,4” - 六-O-乙酰基-6'-O-苯甲酰基-4'-O - [(苯硫基) - 噻吩基] - 五-N-苄氧羰基巴霉素。 由结构式表示的化合物可用于治疗人和动物中的阿米巴痢疾。