diphenylmethyl 7β-phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate | 35246-64-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: diphenylmethyl 7β-phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate
• 英文别名: benzhydryl (6R,7R) -3-(hydroxymethyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate；benzhydryl (6R,7R)-3-(hydroxymethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 35246-64-1
• 化学式: C₂₉H₂₆N₂O₅S
• 分子量: 514.602
• InChiKey: YLOQFPCGJCRAPQ-UFHPHHKVSA-N

物化性质

• 熔点：
  174.5-176 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  810.3±65.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diphenylmethyl 7β-phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate 在 吡啶 、 甲酸 、 五氯化磷 、 sodium carbonate 、 苯甲醚 、 N,N-二甲基苯胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 14.08h， 生成 头孢地尼
  参考文献：
  名称：

  An alternative procedure for preparation of cefdinir

  摘要：

  Cefdinir, a broad spectrum third-generation cephalosporin for oral administration, was prepared by the following synthetic pathway: synthesis of diphenylmethyl 7beta-amino-3-vinyl-3-cephem-4-carboxylate hydrochloride from 7-aminocephalosporanic acid (7-ACA), preparation of sodium 2-(2-tritylaminothiazol-4-yl)-(Z)-2-(tritylhydroxyimino) acetate from ethyl acetoacetate, coupling of both intermediaries to obtain diphenylmethyl 7beta-[2-(2-tritylaminothiazol-4-yl)-(Z)-2-tritylhydroxyimino-3-vinyl-3-cephem-4-carboxylate and final cleavage of trityl and diphenylmethyl protective groups. This procedure allows to obtain better yields of cefdinir and to avoid the use of diketene during the synthesis of this antibiotic by the previously reported method.

  DOI：

  10.1016/s0014-827x(03)00063-6
• 作为产物：
  描述：

  二苯甲酮腙 在 manganese(IV) oxide 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 1.5h， 生成 diphenylmethyl 7β-phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate
  参考文献：
  名称：

  他唑巴坦的高纯度关键中间体的精确制备

  摘要：

  原位红外光谱法用于精确制备高纯度的二苯甲基6α-溴Openicillanate 8，这是他唑巴坦的关键中间体。当6α-溴Openicillanic酸2与二苯基重氮甲烷（DDM）反应时，获得8。2是不稳定的，因此在制备时必须立即与DDM反应。DDM也是不稳定的。由于DDM在制备时会迅速分解，因此无法使用高效液相色谱（HPLC）或气相色谱（GC）精确测定DDM含量。因此，良好的产率和纯度是很难获得的，从而为大批与批料变化（收率69.3-82.8％，纯度89.8-98.4％）8。已开发的8种制备方法涉及使用原位红外监测反应过程并获得了良好的结果（产率为82.7-83.1％，纯度为97.3-98.5％）。该方法还用于制备合成头孢菌素衍生物的关键中间体，具有很高的工业价值。

  DOI：

  10.1021/acs.oprd.0c00407

文献信息

• Cephalosporins, processes for their preparation and pharmaceutical compositions containing them
  申请人：BEECHAM GROUP PLC

  公开号：EP0265185A3

  公开（公告）日：1990-03-28

  Antibacterial agents have the formula (Ia) or are pharmaceutically acceptable salts or invivo hydrolysable esters thereof: wherein R¹ is an acyl group, in particular that of an antibacterially active cephalosporin; R² is hydrogen, methoxy, or formamido; Y is S, SO, SO₂, O or CH₂; X is oxygen, sulphur, or -NH- and R⁴ is a group of the formula CO Z R⁵ wherein Z is -CH=CH-, -(CH₂)n- or -NH-; n is 0, 1 or 2; and R⁵ is: wherein R⁶ and R⁷ are the same or different, each representing hydroxy or protected hydroxy and R⁸ is hydroxy, amino, halogen or carboxy.The use of the compounds of formula (Ia) and intermediates for their preparation are also disclosed.

  抗菌剂的化学式为（Ia），或者是其药用可接受的盐或体内水解酯： 其中R¹是酰基，特别是抗菌活性头孢菌素的酰基；R²是氢、甲氧基或甲酰胺基；Y是S、SO、SO₂、O或CH₂；X是氧、硫或-NH-，R⁴是化学式CO Z R⁵的基团，其中Z是-CH=CH-、-(CH₂)n-或-NH-；n为0、1或2；R⁵是： 其中R⁶和R⁷相同或不同，分别代表羟基或保护羟基，R⁸是羟基、氨基、卤素或羧基。该化合物的使用和其制备的中间体也被披露。
• [EN] CEPHEM COMPOUND<br/>[FR] COMPOSE DE CEPHEM
  申请人：DSM IP ASSETS BV

  公开号：WO2004106347A1

  公开（公告）日：2004-12-09

  The present invention is concerned with a novel cephem compound, with a process for the production of this compound, which process may contain or consist of fermentative steps, chemical steps, and/or biotransformation steps. A cephem compound according to the present invention characterised by formula (I) or a salt or ester thereof, wherein R is selected from the group consisting of (carboxymethylthio)propionyl (carboxyethylthio)propionyl Y- CH2-CO15 wherein Y is phenyl, phenoxy or tetrazolyl HOOC-X-CO wherein X is defined as (CH2)4 or wherein X is defined as (CH2)P-A-(CH2)q, wherein p and q each individually are 0, 1, 2, 3 or 4, and A is CH=CH, C-=C, CHB, C=O, O, S, NH, the nitrogen optionally being substituted or the sulfur optionally being oxidized, and B is hydrogen, halogen, C1-3 alkoxy, hydroxyl, or optionally substituted methyl, with the proviso that p+q should be 2 or 3, when A is CH=CH or C=-C, or p+q should be 3 or 4, when A is CHB, C=O, 0, S or NH or wherein X is (CH2)m-CH=A-(CH2)n or (CH2)m-C=-C-(CH2)n, wherein m and n each individually are 0, 1, 2 or 3 and m+n = 2 or 3, and A is CH or N, or wherein X is (CH2)p-CH=CH-C H=C-(CH2)q wherein p and q each individually are 0 or 1 and p+q = 0 or 1 and wherein R' is selected from the group consisting of OH O-(alkyl 1-6C) wherein the alkyl can be straight or branched and O-C(alkyl 1-6C)-O-(alkyl 1-6C) wherein the alkyl groups can be straight or branched can inter alia be prepared by fermentative techniques according to the invention and in particular using a suitable microorganism possessing or being transformed with the genes needed for conversion of an appropriate acyl-6-aminopenicillanic acid into the desired compound.

  本发明涉及一种新型头孢菌素化合物，以及用于生产该化合物的方法，该方法可以包含或由发酵步骤、化学步骤和/或生物转化步骤构成。根据本发明的头孢菌素化合物的特征是其具有以下式（I）或其盐或酯，其中R选自以下组：（羧甲基硫）丙酰基（羧乙基硫）丙酰基Y- CH2-CO15，其中Y是苯基、苯氧基或四氮唑基HOOC-X-CO，其中X定义为（CH2）4或其中X定义为（CH2）P-A-（CH2）q，其中p和q各自独立地为0、1、2、3或4，A为CH=CH、C-=C、CHB、C=O、O、S、NH，氮原子可选择性地被取代或硫原子可选择性地被氧化，B为氢、卤素、C1-3烷氧基、羟基或可选择性取代的甲基，但要求当A为CH=CH或C=-C时p+q应为2或3，或当A为CHB、C=O、O、S或NH时p+q应为3或4，或其中X为（CH2）m-CH=A-（CH2）n或（CH2）m-C=-C-（CH2）n，其中m和n各自独立地为0、1、2或3且m+n=2或3，A为CH或N，或其中X为（CH2）p-CH=CH-C H=C-（CH2）q，其中p和q各自独立地为0或1且p+q=0或1，且其中R'选自以下组：OH、O-（烷基1-6C），其中烷基可以是直链或支链，或O-C（烷基1-6C）-O-（烷基1-6C），其中烷基可以是直链或支链，可以通过本发明的发酵技术之一制备，特别是使用适当的微生物，该微生物具有或被转化为需要将适当的酰-6-氨基青霉酸转化为所需化合物所需的基因。
• [EN] PRODRUG INHIBITORS<br/>[FR] INHIBITEURS DE PROMÉDICAMENT
  申请人：UNIV LEIDEN

  公开号：WO2020204715A1

  公开（公告）日：2020-10-08

  Provided herein are compounds useful as metallo-β-lactamase (MBL) inhibitors. The compounds have a formula A–B, where A is a β-lactam antibiotic moiety comprising a bridging methylene (-CH2-) covalently attached to -B; and B is a latent MBL inhibitor. Also provided are formulations comprising such compounds; as well as such compounds or formulations for use as a medicament. The compounds and formulations may be used in the treatment of antibiotic resistance, bacterial infection. The compounds and formulations may be used in the inhibition of a bacterial MBL.

  本文提供了作为金属β-内酰胺酶（MBL）抑制剂有用的化合物。这些化合物具有A-B的结构式，其中A是一种β-内酰胺类抗生素基团，包括与-B共价连接的桥联甲基（-CH2-）；而B是一种潜在的MBL抑制剂。还提供了包含这些化合物的配方；以及这些化合物或配方用作药物的用途。这些化合物和配方可用于治疗抗生素耐药性、细菌感染。这些化合物和配方可用于抑制细菌MBL。
• Improved Process For the Preparation of Cephalosporin Antibiotic Intermediate
  申请人：Senthilkumar Udayampalayam Palanisamy

  公开号：US20100261897A1

  公开（公告）日：2010-10-14

  The present invention relates to a process for the production of cephalosporin antibiotic intermediate of formula (I). More particularly relates to the preparation of the compound of formula (I) using a solvent medium selected from the group consisting of decalin (decahydronapthalene), hexane, cyclohexene, tetralin, petroleum ether, wherein X represents HI, HCI, H2SO4 and the like. The compound of formula (I) is an important intermediate in the preparation of Cefepime.

  本发明涉及一种制备头孢菌素抗生素中间体的方法，其化学式为(I)。更具体地，涉及使用从脱氢萘基、己烷、环己烯、四氢萘、石油醚等组成的溶剂介质来制备化合物(I)，其中X代表HI、HCl、H2SO4等。化合物(I)是头孢哌酮制备过程中的重要中间体。
• Design and synthesis of a cephalosporin–carboplatinum prodrug activatable by a β-lactamase
  作者：Stephen Hanessian、Jianguo Wang

  DOI：10.1139/v93-119

  日期：1993.6.1

  The design and syntheses of two cephalosporin–carboplatinum prodrugs that can be released by a β-lactamase are described. The hydrolysis of cephalosporins catalyzed by a β-lactamase with acetyl or DACCP as 3′-leaving groups is studied by ¹H nuclear magnetic resonance in deuterated buffer solutions. These notions provide a new approach to the use of platinum complexes for antitumor therapy.

  本文介绍了两种头孢菌素-卡铂前药的设计和合成，它们可以被β-内酰胺酶释放。使用乙酰基或DACCP作为3'-离去基团的β-内酰胺酶催化的头孢菌素水解反应在氘代缓冲溶液中通过1H核磁共振研究。这些概念为使用铂配合物进行抗肿瘤治疗提供了一种新方法。