(5R,6S)-6-((R)-1-Hydroxy-ethyl)-7-oxo-3-(toluene-4-sulfonyloxy)-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester | 80735-70-2

• 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: (5R,6S)-6-((R)-1-Hydroxy-ethyl)-7-oxo-3-(toluene-4-sulfonyloxy)-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester
• 英文别名: p-nitrobenzyl (5R,6S)-6-[(R)-1-hydroxyethyl]-2-(p-toluenesulfonyloxy)carbapen-2-em-3-carboxylate；(4-nitrophenyl)methyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-3-(4-methylphenyl)sulfonyloxy-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• CAS: 80735-70-2
• 化学式: C₂₃H₂₂N₂O₉S
• 分子量: 502.502
• InChiKey: XURYTEUWXOYDES-LXGCGDOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  164
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (5R,6S)-6-((R)-1-Hydroxy-ethyl)-7-oxo-3-(toluene-4-sulfonyloxy)-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester 生成 p-nitrobenzyl (5R,6S)-2-azido-6-[(R)-1-hydroxyethyl]-carbapen-2-em-3-carboxylate
  参考文献：
  名称：

  CHRISTENSEN, BURTON G.;CHABALA, JOHN C.;RATCLIFFE, RONALD W.

  摘要：

  DOI：
• 作为产物：
  描述：

  亚胺培南母核 生成 (5R,6S)-6-((R)-1-Hydroxy-ethyl)-7-oxo-3-(toluene-4-sulfonyloxy)-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester
  参考文献：
  名称：

  CHRISTENSEN, BURTON G.;RATCLIFFE, RONALD W.;SALZMANN, THOMAS N.

  摘要：

  DOI：

文献信息

• Alternatives to Vinyl Triflates for Cross-Coupling with Arylboronic Acids
  作者：Mark A. Huffman、Nobuyoshi Yasuda

  DOI：10.1055/s-1999-2643

  日期：1999.4

  Vinyl phosphates, mesylates, and tosylates derived from 1,3-dicarbonyl compounds are coupled with phenylboronic acid using nickel or palladium catalysts. An application to the area of 2-aryl carbapenem antibiotics is demonstrated. Alternative conditions for the nickel-catalyzed coupling of aryl mesylates are also reported.

  来自1,3-二酮化合物的乙烯基磷酸酯、甲磺酸酯和对甲苯磺酸酯与苯基硼酸在镍或钯催化剂的作用下进行偶联。还展示了其在2-芳基碳青霉烯抗生素领域的应用。同时还报道了苯基甲磺酸酯的镍催化偶联的替代条件。
• 2-aza-substituted 1-carbadethiapen-2-em-3 carboxylic acids
  申请人：Merck & Co., Inc.

  公开号：US04782051A1

  公开（公告）日：1988-11-01

  Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, trizolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of I from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.2 are, inter alia, hydrogen, alkyl, acyl, and can be joined to form a ring comprising 3 to 7 atoms; R.sup.a is hydrogen, a salt cation, a removable protecting group, or a pharmaceutically acceptable ester moiety. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

  本发明涉及2-氮代取代的1-卡巴德硫杂戊烯-2-乙酸-3-羧酸I，其中通用的2-氮代基包括偶氮基，酰胺基，氨基，烷基氨基，二烷基氨基，三唑基，三唑啉基，环氧乙烷基，以及它们的药学上可接受的盐，酯，酸酐和酰胺衍生物，这些衍生物可用作抗生素。本发明还公开了从已知的适当取代的双环酮酯II通过2-偶氮中间体III制备I的方法：其中R.sup.16为H或CH.sub.3，优选为β-甲基；R.sup.6和R.sup.7分别为氢，线性，支链或环状C.sub.1-C.sub.5烷基，可以用氟，羟基，保护羟基，磺酸基，氨基，保护氨基等取代，其中R.sup.6和R.sup.7一起也可以是C.sub.2-C.sub.4烷基亚甲基，同样取代；条件是R.sup.6和R.sup.7都不是未取代的烷基，R.sup.1和R.sup.2是氢，烷基，酰基等，可以结合形成含有3至7个原子的环；R.sup.a是氢，盐阳离子，可拆卸的保护基或药学上可接受的酯基团。本发明还公开了制备这种化合物的方法；包含这种化合物的药物组合物；以及在需要抗生素效果时，给予这种化合物和组合物的治疗方法。
• 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids
  申请人：Merck & Co., Inc.

  公开号：US04783453A1

  公开（公告）日：1988-11-08

  Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, triazolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of I from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.2 are, inter alia, hydrogen, alkyl, acyl, and can be joined to form a ring comprising 3 to 7 atoms; R.sup.a is hydrogen, a salt cation, a removable protecting group, or a pharmaceutically acceptable ester moiety. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

  本发明涉及2-氮代取代的1-卡巴德硫杂戊烯-2-烯-3-羧酸I，其中一般的2-氮代基包括叠氮基，酰胺基，氨基，烷基氨基，二烷基氨基，三唑基，三唑啉基，环氧丙基，以及它们的药学上可接受的盐，酯，无水物和酰胺衍生物，这些化合物可用作抗生素。还公开了从已知的适当取代的双环酮酯II经2-叠氮中间体III制备I的过程：其中R16为H或CH3，优选为β-甲基；R6和R7独立地为氢，线性，支链或环状C1-C5烷基，可以用氟，羟基，保护羟基，亚磺酸基，氨基，保护氨基取代，其中R6和R7也可以是C2-C4烷基亚甲基，同样取代；但要注意，R6和R7都不是未取代的烷基，R1和R2是氢，烷基，酰基等，可以连接成含3至7个原子的环；R.sup.a是氢，盐阳离子，可去除的保护基或药学上可接受的酯基。还公开了制备这种化合物的方法，包括含有这种化合物的药物组合物以及在需要抗生素效果时给予这种化合物和组合物的治疗方法。
• 2-aza substituted-1-carbadethiapen-2-em-3-carboxylic acids
  申请人：Merck & Co., Inc.

  公开号：US04892869A1

  公开（公告）日：1990-01-09

  Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, triazolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of 1 from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.2 are, inter alia, hydrogen, alkyl, acyl, and can be joined to form a ring comprising 3 to 7 atoms; R.sup.a is hydrogen, a salt cation, a removable protecting group, or a pharmaceutically acceptable ester moiety. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

  本发明涉及2-aza取代的1-carbadethiapen-2-em-3-羧酸I，其中通用的2-aza基团包括azido，acylamino，氨基，烷基氨基，二烷基氨基，三唑基，三唑啉基，环氧乙烷基，以及它们的药学上可接受的盐，酯，酸酐和酰胺衍生物，它们可用作抗生素。还公开了从已知的适当取代的双环酮酯II经2-azido中间体III制备1的过程：其中R16是H或CH3，优选为β-甲基；R6和R7分别是氢，线性，支链或环状C1-C5烷基，可以用氟，羟基，保护羟基，磺酸基，氨基，保护氨基替代，R6和R7取在一起也可以是C2-C4烷基亚甲基，同样取代；但前提是R6和R7都不是未取代的烷基，R1和R2是氢，烷基，酰基等，可以结合形成包含3到7个原子的环；Ra是氢，盐阳离子，可去除的保护基或药学上可接受的酯基。还公开了制备这种化合物的方法；包含这种化合物的制药组合物；以及在抗生素效应指示时，给予这种化合物和组合物的治疗方法。
• Intermediates for the preparation of thienamycin and process for preparing intermediates
  申请人：Merck & Co., Inc.

  公开号：EP0026816A1

  公开（公告）日：1981-04-15

  in a process for the total synthesis of thienamycin from L-aspartic acid via intermediate III: R = H, blocking group or salt cation there is disclosed a process for preparing III via wherein R is a protecting group.

  一种通过中间体 III 从 L-天冬氨酸全合成噻吩霉素的工艺： R = H、封端基团或盐阳离子，公开了一种通过以下方法制备 III 的工艺 其中 R 是保护基团。