(6R)-7t-amino-3-methoxycarbonylmethyl-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester | 63760-52-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (6R)-7t-amino-3-methoxycarbonylmethyl-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
• 英文别名: Diphenylmethyl 3-methoxycarbonylmethyl-7beta-amino-3-cephem-4-carboxylate；benzhydryl (6R,7R)-7-amino-3-(2-methoxy-2-oxoethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 63760-52-1
• 化学式: C₂₃H₂₂N₂O₅S
• 分子量: 438.504
• InChiKey: ORFCHEWUAUXSJW-XMSQKQJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [5-(tert-butoxycarbonylamino-methyl)-thiophen-2-yl]-acetic acid 、 (6R)-7t-amino-3-methoxycarbonylmethyl-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 生成 (6R)-7t-[2-(5-aminomethyl-thiophen-2-yl)-acetylamino]-3-methoxycarbonylmethyl-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Neue ?-Lactam-Antibiotika. Zur Funktionalisierung von 3-Hydroxy-3-cephem-4-carbons�ureestern durch dieWittig-Reaktion. Modifikationen von Antibiotika. 16. Mitteilung [1]

  摘要：

  New β‐lactam antibiotics. Functionalisation of 3‐hydroxy‐3‐cephem‐4‐carboxylic esters through the Wittig reactionThe 3‐hydroxy‐ceph‐3‐em‐esters 1a, b reacted smoothly with stabilized phosphor‐ylids to give a series of derivatives which were converted into the microbiologically active acids 14a, c, 15c and 20 by known procedures. The synthesis of the amides 23, 24, 26 and of the ester 28 from the 3‐carboxymethyl‐derivative 19 is also reported.

  DOI：

  10.1002/hlca.19770600508
• 作为产物：
  描述：

  吡啶 、 五氯化磷 、 (6R)-3-methoxycarbonylmethyl-8-oxo-7t-(2-phenoxy-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 、 、 potassium dihydrogenphosphate 在 ice 、 二氯甲烷 、 氯化钠 、 Sodium sulfate-III 、 crude product 、 silica gel 、 甲苯 、 乙酸乙酯 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 6.5h， 以gives amorphous diphenylmethyl 3-methoxycarbonylmethyl-7β-amino-3-cephem-4-carboxylate, which的产率得到(6R)-7t-amino-3-methoxycarbonylmethyl-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
  参考文献：
  名称：

  Cephem carbonylmethyl derivatives

  摘要：

  该发明涉及公式IA的羰基甲基衍生物和相应的公式IB的羰基亚甲基衍生物，其中R1a表示氢和公式A R.sub.a-C(R.sub.b)(R.sub.c)-C(.dbd.O)-的酰基基团的成员，其中R.sub.a表示可选取代的苯基，噻吩基，呋喃基，环己二烯基和环己烯基的成员，R.sub.b表示氢，R.sub.c表示氢，可选保护的羟基，可选保护的氨基和苯基-较低保护的磺酰基的成员，或者R.sub.a表示氰基，可选取代的苯氧基，吡啶硫基和四氮唑基，R.sub.b和R.sub.c均表示氢，或者R.sub.a表示苯基，噻吩基，呋喃基，R.sub.b和R.sub.c一起表示同构式中的较低烷氧基亚胺基，环烷氧基亚胺基和苯基-较低烷氧基亚胺基，而公式（A）中最多只含有一个游离氨基，R.sub.1.sup.b表示氢，R.sub.2表示羟基，α-多支链较低烷氧基和2-卤代较低烷氧基的成员，可轻易转化为后者，并且还包括苯乙氧基，1-苯基-较低烷氧基，其具有1-3个可选取代的苯基基团，所述取代基为较低烷氧基或硝基，较低烷酰氧甲氧基，α-氨基-较低烷酰氧甲氧基或2-邻苯二甲酰氧基，以及三较低烷基硅氧基，R.sub.3表示氢，较低烷基，环烷基，可选取代的较低烷基，较低烷氧基或卤素的苯基，可选取代的硝基，较低烷基，较低烷氧基或卤素的苯基-较低烷基，羟基，醚化的羟基，尤其是较低烷氧基，特别是甲氧基，氨基，较低烷基氨基，二较低烷基氨基，较低烷基亚烷基氨基，氧较低烷基亚烷基氨基，苯基氨基，羟基氨基，较低烷氧基氨基，肼基，2-较低烷基肼基，2-苯基肼基，4-较低烷基哌嗪-1-基氨基，被氨基和/或羧基取代的较低烷基氨基和可选取代的较低烷基的杂环基氨基，其中杂环基基团最好包含5-6个环成员并包含氮，该氮可以是N-氧化形式，氧或硫，以及这些化合物的1-氧化物和盐，这些化合物对微生物具有活性，例如革兰氏阳性和革兰氏阴性细菌，并且药物制剂含有这些化合物。

  公开号：

  US04248868A1

文献信息

• US4248868A
  申请人：——

  公开号：US4248868A

  公开（公告）日：1981-02-03
• Neue ?-Lactam-Antibiotika. Zur Funktionalisierung von 3-Hydroxy-3-cephem-4-carbons�ureestern durch dieWittig-Reaktion. Modifikationen von Antibiotika. 16. Mitteilung [1]
  作者：Riccardo Scartazzini

  DOI：10.1002/hlca.19770600508

  日期：1977.7.13

  New β‐lactam antibiotics. Functionalisation of 3‐hydroxy‐3‐cephem‐4‐carboxylic esters through the Wittig reactionThe 3‐hydroxy‐ceph‐3‐em‐esters 1a, b reacted smoothly with stabilized phosphor‐ylids to give a series of derivatives which were converted into the microbiologically active acids 14a, c, 15c and 20 by known procedures. The synthesis of the amides 23, 24, 26 and of the ester 28 from the 3‐carboxymethyl‐derivative 19 is also reported.
• Cephem carbonylmethyl derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US04248868A1

  公开（公告）日：1981-02-03

  The invention comprises carbonylmethyl derivatives of the formula IA and corresponding carbonylmethylene derivatives of the formula IB ##STR1## in which R.sub.1.sup.a represents a member of the group comrising hydrogen and an acyl radical of the formula A R.sub.a --C(R.sub.b)(R.sub.c)--C(.dbd.O)-- (A) in which R.sub.a represents a member of the group comprising optionally substituted phenyl, thienyl, furyl, cyclohexadienyl and cyclohexenyl, R.sub.b represents hydrogen and R.sub.c represents a member of the group comprising hydrogen, optionally protected hydroxyl, optionally protected amino and phenyl-lower protected sulpho, or in which R.sub.a represents a member of the group comprising cyano, optionally substituted phenoxy, pyridylthio, and tetrazolyl, and R.sub.b and R.sub.c each represent hydrogen, or in which R.sub.a represents a member of the group comprising phenyl, thienyl, furyl, and R.sub.b and R.sub.c together denote a member of the group comprising lower alkoxyimino, cycloalkoxyimino and phenyl-lower alkoxyimino in the syn-configuration, and such a group of the formula (A) contains at most one free amino group, R.sub.1.sup.b represents hydrogen, R.sub.2 represents a member of the group comprising hydroxyl, .alpha.-poly-branched lower alkoxy and 2-halogeno-lower alkoxy, which can easily be converted into the latter, and also phenacyloxy, 1-phenyl-lower alkoxy which has 1-3 phenyl radicals which are optionally substituted by lower alkoxy or nitro, lower alkanoyloxymethoxy, .alpha.-amino-lower alkanoyloxymethoxy, or 2-phthalidyloxy, and also tris-lower alkylsilyloxy, and R.sub.3 represents a member of the group comprising hydrogen, lower alkyl, cycloalkyl, phenyl which is optionally substituted by lower alkyl, lower alkoxy or halogen, phenyllower alkyl which is optionally substituted by nitro, lower alkyl, lower alkoxy or halogen, hydroxyl, etherified hydroxyl, especially lower alkoxy, above all methoxy, amino, lower alkylamino, di-lower alkylamino, lower alkyleneamino, oxa-lower alkylenamino, phenylamino, hydroxylamino, lower alkoxyamino, hydrazino, 2-lower alkylhydrazino, 2-phenylhydrazino, 4-lower alkylpiperazin-1-ylamino, lower alkylamino which is substituted by amino and/or carboxyl, and heterocyclylamino which is optionally substituted by lower alkyl, and wherein the heterocyclyl radical preferably contains 5-6 rings members and contains, as hetero-atoms, nitrogen, which is optionally also in the N-oxidized form, oxygen or sulphur and 1-oxides and salts of such compounds, which compounds are active against microorganisms, such as Gram-positive and Gram-negative bacteria, and pharmaceutical preparations containing these compounds.

  该发明涉及公式IA的羰基甲基衍生物和相应的公式IB的羰基亚甲基衍生物，其中R1a表示氢和公式A R.sub.a-C(R.sub.b)(R.sub.c)-C(.dbd.O)-的酰基基团的成员，其中R.sub.a表示可选取代的苯基，噻吩基，呋喃基，环己二烯基和环己烯基的成员，R.sub.b表示氢，R.sub.c表示氢，可选保护的羟基，可选保护的氨基和苯基-较低保护的磺酰基的成员，或者R.sub.a表示氰基，可选取代的苯氧基，吡啶硫基和四氮唑基，R.sub.b和R.sub.c均表示氢，或者R.sub.a表示苯基，噻吩基，呋喃基，R.sub.b和R.sub.c一起表示同构式中的较低烷氧基亚胺基，环烷氧基亚胺基和苯基-较低烷氧基亚胺基，而公式（A）中最多只含有一个游离氨基，R.sub.1.sup.b表示氢，R.sub.2表示羟基，α-多支链较低烷氧基和2-卤代较低烷氧基的成员，可轻易转化为后者，并且还包括苯乙氧基，1-苯基-较低烷氧基，其具有1-3个可选取代的苯基基团，所述取代基为较低烷氧基或硝基，较低烷酰氧甲氧基，α-氨基-较低烷酰氧甲氧基或2-邻苯二甲酰氧基，以及三较低烷基硅氧基，R.sub.3表示氢，较低烷基，环烷基，可选取代的较低烷基，较低烷氧基或卤素的苯基，可选取代的硝基，较低烷基，较低烷氧基或卤素的苯基-较低烷基，羟基，醚化的羟基，尤其是较低烷氧基，特别是甲氧基，氨基，较低烷基氨基，二较低烷基氨基，较低烷基亚烷基氨基，氧较低烷基亚烷基氨基，苯基氨基，羟基氨基，较低烷氧基氨基，肼基，2-较低烷基肼基，2-苯基肼基，4-较低烷基哌嗪-1-基氨基，被氨基和/或羧基取代的较低烷基氨基和可选取代的较低烷基的杂环基氨基，其中杂环基基团最好包含5-6个环成员并包含氮，该氮可以是N-氧化形式，氧或硫，以及这些化合物的1-氧化物和盐，这些化合物对微生物具有活性，例如革兰氏阳性和革兰氏阴性细菌，并且药物制剂含有这些化合物。