(5R)-6t-((R)-1-hydroxy-ethyl)-3,3-dimethyl-7-oxo-(5rH)-4-thia-1-aza-bicyclo[3.2.0]heptane-2c-carboxylic acid | 62263-80-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (5R)-6t-((R)-1-hydroxy-ethyl)-3,3-dimethyl-7-oxo-(5rH)-4-thia-1-aza-bicyclo[3.2.0]heptane-2c-carboxylic acid
• 英文别名: (2S,5R,6R)-6-[(1R)-1-hydroxyethyl]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
• CAS: 62263-80-3
• 化学式: C₁₀H₁₅NO₄S
• 分子量: 245.299
• InChiKey: MPTLCUDUQPXSPL-MNCSTQPFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-Nitrobenzyl 6,6-dibromopenicillanate 在 palladium on activated charcoal 三丁基膦 、 甲基溴化镁 、 氢气 作用下， 以 甲醇 为溶剂， 生成 (5R)-6t-((R)-1-hydroxy-ethyl)-3,3-dimethyl-7-oxo-(5rH)-4-thia-1-aza-bicyclo[3.2.0]heptane-2c-carboxylic acid
  参考文献：
  名称：

  Quantification of the extent of attenuation of the rate of turnover chemistry of the TEM-1 β-lactamase by the α-1R-hydroxyethyl group in substrates

  摘要：

  The 6 alpha-1R-hydroxyethyl group of imipenem, a clinically used carbapenem antibacterial agent, is believed to displace the hydrolytic water from its optimal position in the active site of class A beta-lactamases. This interaction renders the molecule a poor substrate for these bacterial enzymes, hence preserving the antibacterial property of the antibiotic. The extent of the contribution of the 6 alpha-1R-hydroxyethyl group in substrates toward stabilization of the antibiotic to the hydrolytic action of class A TEM-1 beta-lactamase was studied by the synthesis and evaluation of two penicillanic acid derivatives, 6 alpha-(1R-hydroxyethyl)penicillanic acid (2) and 6 beta-(1R-hydroxyethyl)penicillanic acid (3). The kinetic evaluation of the enzymic hydrolysis of these two penicillanic acid derivatives indicated that the 6 alpha-1R-hydroxyethyl group imparts as much as 10(4)-fold to the hydrolytic stability of the beta-lactam substrate.

  DOI：

  10.1016/0960-894x(96)00022-4

文献信息

• US4720490A
  申请人：——

  公开号：US4720490A

  公开（公告）日：1988-01-19
• [EN] FLUORALKYLATEDCARBAPENEM DERIVATIVES
  申请人：——

  公开号：WO1984000547A1

  公开（公告）日：1984-02-16

  (EN) Compounds of formula (I), wherein, R1 represents hydrogen or methyl and R2 represents hydrogen or lower alkyl, lower alkenyl or cycloalkyl each of which may be unsubstituted or mono- or polysubstituted by amino, mono- or di-(lower)-alkylamino, lower acylamino, carboxy, lower alkoxycarbonyl or carbamoyl; a group of formula IIc: (CH2)p-R7, wherein R7 represents phenyl or a 5- or 6-membered saturated or unsaturated heterocycle containing one or more heteroatoms selected from 0, S and/or N and which may be unsubstituted or mono- or polysubstituted by fluoro, chloro, bromo, amino, mono- or di-(lower)-alkylamino, hydroxy, lower alkoxy, mercapto, alkylthio, phenylthio, sulfamoyl, guanidino, nitro, cyano, lower acylamino, carboxyl, alkoxycarbonyl or carbamoyl and p is 0, 1, 2 or 3; or a group of formula (II), (IIa), (IIb), wherein R4, R5 and R6 may be the same or different and each represents hydrogen or lower alkyl or R4 and R6 and/or R5 and one of the CH2 groups may be joined to form a ring as may R5 and R6 in formula II and R4 and R5 in IIa and IIb, which rings may be unsubstituted or mono- or poly-substituted by alkyl, hydroxy, carboxy or di-(lower)-alkylamino, m is 2 or 3, and n is 1, 2 or 3 with the proviso that when R1 is hydrogen and the group containing it has R-configuration, R2 is other than acetylaminoethyl; or protected forms and/or physiologically-hydrolysable and acceptable ester forms thereof; in free acid or salt form or in the form of zwitter-ions. The compounds exhibit chemotherapeutic properties and are particularly indicated for use as anti-bacterially active antibiotics. (FR) Composés de formule (I) où R1 représente un hydrogène ou un méthyl et R2 représente un hydrogène ou un alkyl inférieur, un alkényl inférieur ou un cycloalkyl, chacun desquels peut être non substitué ou mono-ou polysubstitué par un amino, un monoalkylamino ou un dialkylamino inférieur, un acylamino inférieur, un carboxy, un alkoxycarbonyl inférieur ou un carbamoyle. Un groupe correspondant à la formule (IIc) où R7 représente un phényl ou un éthérocycle saturé ou insaturé à 5 ou 6 membres contenant un ou plusieurs éthéroatomes sélectionnés à partir de O, S et/ou N et qui peut être non subsitué ou mon-ou polysubstitué par du fluor, chlore, braume, amino, monoalkylamino ou dialkylamino inférieur, hydroxy, alkoxy inférieur, mercapto, alkylthio, phénylthio, sulfamoyl, guanidino, nitro, cyano, acylamino inférieur, carboxyl, alkoxycarbonyl ou carbamoyl et p vaut 0, 1, 2 ou 3; ou un groupe de formule (II), (IIa) et (IIb), où R4, R5 et R6 peuvent être identiques ou différents et représentent chacun un hydrogène ou alkyl inférieur ou R4 et R6 et/ou R5 et un des groupes CH2 peuvent être reliés pour former un cycle, de même que pour R5 et R6 dans la formule (II) et R4 et R5 dans la formule (IIa) et (IIb), ces cycles pouvant être non substitués ou mono- ou polysubstitués par un alkyl, un hydroxy, un carboxy ou un dialkylamino inférieur, M vaut 2 ou 3, et n vaut 1, 2 ou 3, à condition que lorsque R1 est un hydrogène et le groupe le contenant possède une configuration R, R2 n"est pas un acétylaminoéthyl; formes protégées et/ou formes d"ester physiologiquement hydrolysables et acceptables de ces composés; sous forme de sels ou d"acides libres ou sous forme d"ions amphotériques. Ces composés présentent des propriétés chimiothérapeutiques et sont particulièrement indiqués pour être utilisés comme antibiotiques à action antibactérienne.
• Quantification of the extent of attenuation of the rate of turnover chemistry of the TEM-1 β-lactamase by the α-1R-hydroxyethyl group in substrates
  作者：Kazuyuki Miyashita、Irina Massova、Shahriar Mobashery

  DOI：10.1016/0960-894x(96)00022-4

  日期：1996.2

  The 6 alpha-1R-hydroxyethyl group of imipenem, a clinically used carbapenem antibacterial agent, is believed to displace the hydrolytic water from its optimal position in the active site of class A beta-lactamases. This interaction renders the molecule a poor substrate for these bacterial enzymes, hence preserving the antibacterial property of the antibiotic. The extent of the contribution of the 6 alpha-1R-hydroxyethyl group in substrates toward stabilization of the antibiotic to the hydrolytic action of class A TEM-1 beta-lactamase was studied by the synthesis and evaluation of two penicillanic acid derivatives, 6 alpha-(1R-hydroxyethyl)penicillanic acid (2) and 6 beta-(1R-hydroxyethyl)penicillanic acid (3). The kinetic evaluation of the enzymic hydrolysis of these two penicillanic acid derivatives indicated that the 6 alpha-1R-hydroxyethyl group imparts as much as 10(4)-fold to the hydrolytic stability of the beta-lactam substrate.