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    Bioprocesses for preparing 7-ACA and 7-ADAC
    2.
    发明授权
    Bioprocesses for preparing 7-ACA and 7-ADAC 失效
    用于制备7-ACA和7-ADAC的生物工艺

    公开(公告)号：US6071713A

    公开(公告)日：2000-06-06

    申请号：US340781

    申请日：1999-06-28

    申请人： Michael J. Conder ,  John A. Rambosek ,  Phyllis C. McAda ,  Christopher D. Reeves

    发明人： Michael J. Conder ,  John A. Rambosek ,  Phyllis C. McAda ,  Christopher D. Reeves

    IPC分类号： C12N1/19 ,  C07D501/20 ,  C12N1/15 ,  C12N9/00 ,  C12N9/02 ,  C12N9/10 ,  C12N15/09 ,  C12N15/52 ,  C12N15/54 ,  C12P20060101 ,  C12P35/00 ,  C12P35/06 ,  C12P37/04 ,  C12R1/82 ,  C12N1/14 ,  C12N1/20 ,  C12P35/02

    CPC分类号： C12N9/0071 ,  C12N9/00 ,  C12N9/1029 ,  C12P35/00 ,  C12P37/04 ,  Y10S435/935

    摘要： A bioprocess for preparing adipoyl-7-ACA comprising the steps: (a) transforming cells of a strain of Penicillium chrysogenum which produces isopenicillin N with an expression vector containing DNA encoding an enzyme, having expandase activity capable of accepting adipoyl 6-APA as a substrate, an enzyme having hydroxylase activity capable of accepting adipoyl-7-ADCA as a substrate and an enzyme having acetyl transferase activity capable of accepting adipoyl 7-ADAC as a substrate; (b) culturing the transformed cells from step a) in a suitable culture medium containing an adipate feedstock, wherein said cells produce adipoyl 6-APA; and (c) culturing the transformed cells producing adipoyl 6-APA of step b) under conditions suitable for expression of said DNA encoding enzyme, thereby producing the end product adipoyl-7-ACA.

    摘要翻译： 一种用于制备己二酰-7-ACA的生物工艺，包括以下步骤：（a）用含有编码酶的DNA的表达载体转化产生异青霉素N的产青霉菌菌株的细胞，其具有能够接受己二酰基6-APA的扩环酶活性 底物，能够接受己二酰-7-ADCA作为底物的羟化酶活性的酶和能够接受己二酰基7-ADAC作为底物的乙酰转移酶活性的酶; （b）在含有己二酸原料的合适培养基中培养来自步骤a）的转化细胞，其中所述细胞产生己二酰基6-APA; 和（c）在适于表达所述DNA编码酶的条件下培养产生步骤b）的己二酰基6-APA的转化细胞，从而产生最终产物己二酰-7-ACA。

    Cephem compound, its production and its use for producing cephem antibiotics
    4.
    发明授权
    Cephem compound, its production and its use for producing cephem antibiotics 失效
    Cephem化合物，其生产及其用于生产头孢类抗生素的用途

    公开(公告)号：US5969131A

    公开(公告)日：1999-10-19

    申请号：US932835

    申请日：1997-09-18

    申请人： Mari Yuasa ,  Kazuyuki Yamagata ,  Hirokazu Murata ,  Masashi Komatsu ,  Isao Yoshida

    发明人： Mari Yuasa ,  Kazuyuki Yamagata ,  Hirokazu Murata ,  Masashi Komatsu ,  Isao Yoshida

    IPC分类号： C07D501/16 ,  C07D501/00 ,  C07D501/04 ,  C07D501/18 ,  C07D501/20 ,  C07D501/22 ,  C07D501/24 ,  C07D501/56

    CPC分类号： C07D501/00 ,  Y02P20/55

    摘要： A 3-[(E)-1-propenyl]cephem compound represented by formula (I): ##STR1## wherein R represents hydrogen, a protective group for an amino group, or the group shown by formula (II): ##STR2## in which R.sup.3 is a protective group for an amino group, R.sup.4 is a protective group for a hydroxyl group, and W is --CH.dbd. or --N.dbd.; R.sup.2 represents a protective group for a carboxyl group; and X represents hydrogen or chlorine. The compound is useful as an intermediate for producing cephem antibiotics and is prepared by isomerizing the corresponding 3-[(Z)-1-propenyl]cephem compound in an inert organic solvent in the presence of an aromatic thiol. The compound of formula (I) wherein X is chlorine can be converted into a 3-[(E)-3-ammonio-1-propenyl]cephem derivative through the reaction with a tertiary amine.

    摘要翻译： 由式（I）表示的3 - [（E）-1-丙烯基]头孢烯化合物：其中R表示氢，氨基保护基或式（II）所示的基团：其中R3为保护基 氨基的基团，R4是羟基的保护基，W是-CH =或-N =; R2表示羧基的保护基; X表示氢或氯。 该化合物可用作生产头孢类抗生素的中间体，并且通过在惰性有机溶剂中在芳族硫醇存在下使相应的3 - [（Z）-1-丙烯基]头孢烯化合物异构化而制备。 其中X为氯的式（I）化合物可通过与叔胺的反应转化为3 - [（E）-3-氨基-1-丙烯基]头孢烯衍生物。

    Fluorogenic substrates for .beta.-lactamase and methods of use
    5.
    发明授权
    Fluorogenic substrates for .beta.-lactamase and methods of use 失效
    β-内酰胺酶的荧光底物和使用方法

    公开(公告)号：US5741657A

    公开(公告)日：1998-04-21

    申请号：US407544

    申请日：1995-03-20

    申请人： Roger Y. Tsien ,  Gregor Zlokarnik

    发明人： Roger Y. Tsien ,  Gregor Zlokarnik

    IPC分类号： C12N15/09 ,  C07D463/00 ,  C07D471/04 ,  C07D501/00 ,  C07D501/20 ,  C07D501/59 ,  C07D505/00 ,  C12N5/02 ,  C12N5/10 ,  C12N9/86 ,  C12N15/55 ,  C12N15/85 ,  C12P17/18 ,  C12P35/00 ,  C12Q1/34 ,  C12Q1/68 ,  C07D501/14

    CPC分类号： C07D501/36 ,  C07D501/00 ,  C07D505/00 ,  C07D519/00 ,  C12N15/85 ,  C12N9/86 ,  C12P17/184 ,  C12P17/188 ,  C12P35/00 ,  C12Q1/18 ,  C12Q1/34 ,  C12Q1/6897 ,  C12N2800/90 ,  C12N2830/002 ,  C12Q2334/00 ,  G01N2333/986 ,  G01N2415/00 ,  Y10S435/805

    摘要： Fluorogenic substrates of the general formula I ##STR1## in which one of X and Y is a fluorescent donor moiety and the other is a quencher (which may or may not re-emit); R' is selected from the group consisting of H, lower (i.e., alkyl of 1 to about 5 carbon atoms) and (CH.sub.2 OH).sub.n OH, in which n is 0 or an integer from 1 to 5; R" is selected from the group consisting of H, physiologically acceptable metal and ammonium cations, --CHR.sup.2 OCO(CH.sub.2).sub.n CH.sub.3, --CHR.sup.2 OCOC(CH.sub.3).sub.3, acylthiomethyl, acyloxy-alpha-benzyl, delta-butyrolactonyl, methoxycarbonyloxymethyl, phenyl, methylsulphinylmethyl, beta-morpholinoethyl, dialkylaminoethyl, acyloxyalkyl, dialkylaminocarbonyloxymethyl and aliphatic, in which R.sup.2 is selected from the group consisting of H and lower alkyl; A is selected from the group consisting of S, O, SO, SO.sub.2 and CH.sub.2 ; and Z' and Z" are linkers for the fluorescent donor and quencher moieties. The substrates are useful in conjunction with .beta.-lactamase as reporter gene in a wide range of assays, for example to determine protein localization or bacterial resistance.

    摘要翻译： 其中X和Y中的一个是荧光供体部分，另一个是淬灭剂（其可以或不再发射）的通式I 的荧光底物; R'选自H，低级（即1至约5个碳原子的烷基）和（CH 2 OH）nOH，其中n为0或1至5的整数; R“选自H，生理学上可接受的金属和铵阳离子，-CHR2OCO（CH2）nCH3，-CHR2OCOC（CH3）3，酰基硫代甲基，酰氧基-α-苄基，δ-丁基内酰基，甲氧基羰氧基甲基，苯基，甲基亚磺酰基甲基 ，β-吗啉代乙基，二烷基氨基乙基，酰氧基烷基，二烷基氨基羰氧基甲基和脂族基，其中R2选自H和低级烷基; A选自S，O，SO，SO 2和CH 2; Z'和Z“是荧光供体和猝灭剂部分的接头。 在广泛的测定中，底物可与β内酰胺酶作为报告基因结合使用，例如确定蛋白质定位或细菌耐药性。

    Bicyclic .beta.-lactams intermediates having a new amino protecting group
    9.
    发明授权
    Bicyclic .beta.-lactams intermediates having a new amino protecting group 失效
    具有新的氨基保护基团的双环β-内酰胺中间体

    公开(公告)号：US5453504A

    公开(公告)日：1995-09-26

    申请号：US309840

    申请日：1994-09-21

    申请人： Leland O. Weigel

    发明人： Leland O. Weigel

    IPC分类号： C07C231/10 ,  C07D205/085 ,  C07D403/04 ,  C07D403/12 ,  C07D405/14 ,  C07D463/00 ,  C07D501/04 ,  C07D501/20

    CPC分类号： C07D403/04 ,  C07C231/10 ,  C07D205/085 ,  C07D403/12 ,  C07D405/14 ,  Y02P20/55

    摘要： A method for preparing a new class of protected amino intermediates is provided which utilizes reaction of an imido protected primary amine with a secondary amine. The intermediates thus provided are suitably protected for nucleophilic functionalization on the residue of the primary amine. The desired imido protected amine thus derivatized may be regenerated using acid. Further provided are methods for resolving racemic primary amines. Also provided are .beta.-lactam intermediates protected with the new amino protecting group which are useful in the preparation of .beta.-lactam antibiotics.

    摘要翻译： 提供了一种制备新类型的受保护的氨基中间体的方法，其利用亚胺基保护的伯胺与仲胺的反应。 由此提供的中间体适当地保护在伯胺残基上进行亲核官能化。 因此衍生化的所需酰亚胺保护的胺可以使用酸再生。 还提供了拆分外消旋伯胺的方法。 还提供了用新的氨基保护基团保护的β-内酰胺中间体，其可用于制备β-内酰胺抗生素。