4-Nitrobenzyl (1R, 5S,6S)-6-[1(R)-t-butyldimethylsilyloxyethyl]-1-methyl-2-phenylthio-1-carbapen-2-em-3-carboxylate | 105344-46-5

• 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: 4-Nitrobenzyl (1R, 5S,6S)-6-[1(R)-t-butyldimethylsilyloxyethyl]-1-methyl-2-phenylthio-1-carbapen-2-em-3-carboxylate
• 英文别名: (4-nitrophenyl)methyl (4R,5S,6S)-6-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-methyl-7-oxo-3-phenylsulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• CAS: 105344-46-5
• 化学式: C₂₉H₃₆N₂O₆SSi
• 分子量: 568.766
• InChiKey: CQEWZMGGDTUUIW-DJEYIWCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.53
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  127
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-Nitrobenzyl (1R, 5S,6S)-6-[1(R)-t-butyldimethylsilyloxyethyl]-1-methyl-2-phenylthio-1-carbapen-2-em-3-carboxylate 在 硝基甲烷 、 四氯化钛 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 以89%的产率得到4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-phenylthio-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
  参考文献：
  名称：

  Efficient Method for the Deprotection of tert-Butyldimethylsilyl Ethers with TiCl₄−Lewis Base Complexes:  Application to the Synthesis of 1β-Methylcarbapenems

  摘要：

  TiCl4-Lewis base (AcOEt, CH3NO2) complexes smoothly deprotected tert-butyldimethylsilyl (TBDMS) ethers. The reaction velocity with these complexes, which seemed less reactive due to the influence of Lewis bases, was considerably greater than that with TiCl4 alone. Selective desilylations between aliphatic and aromatic TBDMS ethers (1 and 5), between 1 and benzyl, allyl, tosyl, methoxyphenyl, and chloroacetyl ethers (13, 14, 15, 16, and 17), and between TBDMS and TBDPS ethers (18 and 19) were successfully performed. Desilylation of TBDMS-aldol, acyloin, and beta-lactam analogues 9-12 proceeded smoothly due to anchimeric assistance by the neighboring carbonyl groups. The present method was successfully applied to the practical synthesis of 1 beta-methylcarbapenems 20a'-f'.

  DOI：

  10.1021/jo0604484
• 作为产物：
  描述：

  (4-硝基苯基)甲基 (2-巯基乙基)氨基甲酸酯 在 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 magnesium bromide 作用下， 以 四氢呋喃 为溶剂， 反应 1.67h， 生成 4-Nitrobenzyl (1R, 5S,6S)-6-[1(R)-t-butyldimethylsilyloxyethyl]-1-methyl-2-phenylthio-1-carbapen-2-em-3-carboxylate
  参考文献：
  名称：

  2-芳基亚磺酰基和2-芳基磺酰基中间体的侧链取代反应为1β-甲基卡宾

  摘要：

  衍生自1β-甲基卡巴南4的亚砜5和砜6通过MgBr 2 ·Et 2 O介导的C-2侧链取代反应与官能化的硫醇反应生成1β-甲基卡巴南的前体。

  DOI：

  10.1016/s0040-4039(97)01239-2

文献信息

• Practical Synthesis of 1.BETA.-Methylcarbapenem Antibiotics: Side Chain Substitution Reaction of 2-Arylsulfinyl and 2-Arylsulfonyl Carbapenems.
  作者：Kozo ODA、Akira YOSHIDA

  DOI：10.1248/cpb.46.893

  日期：——

  The C-2 side-chain substitution reaction of a sulfoxide and a sulfone derived from a p-nitrobenzyl (1R, 5S, 6S)-6-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-[2-(diethylcarbamoyl)phenylthio]-1-methylcarbapen-2-em-3-carboxylate with various mercaptans progressed smoothly in the presence of magnesium bromide. Bromomagnesium thiolate prepared from mercaptans proved to be especially effective for the substitution reaction and gave precursors of 1β-methylcarbapenem antibiotics in high yield.

  由对硝基苄基 (1R,5S,6S)-6-[(1R)-1-(叔丁基二甲基硅氧基)乙基]-2-[2-(二乙基氨基甲酰基)苯硫基]-1-甲基碳青霉烯-2-em-3-甲酸酯衍生的亚砜和砜与各种硫醇的 C-2 侧链取代反应在溴化镁存在下进展顺利。由硫醇制备的硫酸溴镁被证明对取代反应特别有效，并能以高产率得到 1β- 甲基碳青霉烯类抗生素的前体。
• Synthetic Studies of Carbapenem and Penem Antibiotics. V. Efficient Synthesis of the 1.BETA.-Methylcarbapenem Skeleton.
  作者：Makoto SUNAGAWA、Akira SASAKI、Haruki MATSUMURA、Koshiro GODA、Katsumi TAMOTO

  DOI：10.1248/cpb.42.1381

  日期：——

  An efficient synthesis of 1β-methylcarbapenem from the 1-(2-oxoazetidinyl)acetate 8 was developed by application of the Dieckmann reaction. Dieckmann-type cyclization of 8 and conversion to the enolphosphate 10 were achieved without epimerization to the 1α-methyl isomer in a one-pot procedure. Treatment with the mercaptan 22 after the phosphorylation resulted in a practical one-pot preparation of the 1β-methylcarbapenem derivative 23 from 8.

  通过应用 Dieckmann 反应，开发了从 1-(2-氧代氮杂环丁酯)乙酸酯 8 高效合成 1β-甲基碳青霉烯的方法。 8 的 Dieckmann 型环化和烯醇磷酸 10 的转化是通过一锅法实现的，无需差向异构化为 1α-甲基异构体。磷酸化后用硫醇22处理导致从8中一锅法制备出1β-甲基碳青霉烯衍生物23。
• Metal catalyzed displacement process
  申请人：Sankyo Company, Limited

  公开号：US05681951A1

  公开（公告）日：1997-10-28

  A process for preparing a compound of formula (I'): ##STR1## comprising reacting a compound of formula (II'): ##STR2## with a compound of formula (III'): A'SH (III') wherein the reaction of the compound of formula (II') and the compound of formula (III') are carried out in the presence of a salt of a metal of Group II or III of the Periodic Table of Elements, wherein A' is an alkyl, aryl, aralkyl or heterocyclic, R.sup.1' is hydrogen or a carboxy protecting group, R.sup.2' and R.sup.3' can be hydrogen or alkyl, X' can be sulfur, k' is 1 or 2 and R.sup.4' is alkyl, alkenyl, aryl, aralkyl, cycloalkyl or heterocyclic.

  一种制备式（I'）化合物的方法： ##STR1## 包括将式（II'）化合物与式（III'）化合物反应： ##STR2## 其中化合物（II'）和化合物（III'）的反应在元素周期表II或III族金属的盐的存在下进行，其中A'是烷基，芳基，芳烷基或杂环基，R.sup.1'是氢或羧基保护基，R.sup.2'和R.sup.3'可以是氢或烷基，X'可以是硫，k'为1或2，R.sup.4'是烷基，烯基，芳基，芳烷基，环烷基或杂环基。
• Azetidinone compounds useful in the preparation of carbapenem
  申请人：Sankyo Company, Limited

  公开号：US05541317A1

  公开（公告）日：1996-07-30

  Compounds of formula (I): ##STR1## wherein: R.sup.1 is hydrogen or a hydroxy-protecting group; R.sup.2 is alkyl, alkoxy, halogen, optionally substituted phenyl or optionally substituted phenoxy; R.sup.3 is optionally substituted pyridyl, optionally substituted quinolyl or phenyl group which has a substituent of formula --CYNR.sup.5 R.sup.6, where Y is oxygen or sulfur, and R.sup.5 and R.sup.6 are each alkyl, aryl or aralkyl, or R.sup.5 and R.sup.6 and the nitrogen to which they are attached together form a heterocyclic group; is R.sup.4 hydrogen or an amino-protecting group; and Z is sulfur or oxygen; are valuable intermediates in the preparation of carbapenem compounds and retain a desirable configuration during conversion to such carbapenem compounds. Penem and carbapenem compounds having a group of formula --SA' are prepared from a corresponding compound having a substituted thio, sulfinyl or sulfonyl group at this position by reaction with a compound A'SH (where A' is an organic group) in the presence of a salt of a metal of Group II or III of the Periodic Table.

  化合物的式子(I)：##STR1## 其中：R.sup.1为氢或羟基保护基；R.sup.2为烷基，烷氧基，卤素，可选择取代的苯基或可选择取代的苯氧基；R.sup.3为可选择取代的吡啶基，可选择取代的喹啉基或具有式子--CYNR.sup.5 R.sup.6的取代基的苯基，其中Y为氧或硫，而R.sup.5和R.sup.6均为烷基，芳基或芳基烷基，或R.sup.5和R.sup.6以及它们所连接的氮共同形成一个杂环基团；R.sup.4为氢或氨基保护基；Z为硫或氧；是制备碳青霉烯化合物的有价值的中间体，并在转化为碳青霉烯化合物期间保持理想的构型。具有式子--SA'的青霉烯和碳青霉烯化合物是通过与具有该位置的取代硫，亚砜或磺酰基的相应化合物在周期表第二或第三组金属的盐存在下与化合物A'SH（其中A'是有机基团）反应制备的。
• Silyl enol ether alkylation process
  申请人：Sankyo Company, Limited

  公开号：US05719275A1

  公开（公告）日：1998-02-17

  A method for preparing compounds of formula (I): ##STR1## wherein: R.sup.1 is hydrogen or a hydroxy-protecting group; R.sup.2 is alkyl, alkoxy, halogen, optionally substituted phenyl or optionally substituted phenoxy; R.sup.3 is optionally substituted pyridyl, optionally substituted quinolyl or phenyl group which has a substituent of formula --CYNR.sup.5 R.sup.6, where Y is oxygen or sulfur, and R.sup.5 and R.sup.6 are each alkyl, aryl or aralkyl, or R.sup.5 and R.sup.6 and the nitrogen to which they are attached together form a heterocyclic group; R.sup.4 is hydrogen or an amino-protecting group; and Z is sulfur or oxygen. The process comprises reacting a compound of formula (II): ##STR2## in which R.sup.8, R.sup.9 and R.sup.10 are the same or different and each represents an alkyl group having from 1 to 4 carbon atoms or a phenyl group, with a compound of formula (III): ##STR3## in which R.sup.11 represents an acyloxy, alkylsulfonyl, arylsulfonyl, alkylsulfinyl or arylsulfinyl group.

  一种制备式（I）化合物的方法：其中：R.sup.1是氢或羟基保护基；R.sup.2是烷基，烷氧基，卤素，可选地取代的苯基或可选地取代的苯氧基；R.sup.3是可选地取代的吡啶基，可选地取代的喹啉基或具有式--CYNR.sup.5 R.sup.6的取代基的苯基，其中Y是氧或硫，R.sup.5和R.sup.6分别是烷基，芳基或芳烷基，或R.sup.5和R.sup.6和它们所连接的氮共同形成一个杂环基；R.sup.4是氢或氨基保护基；Z是硫或氧。该过程包括将式（II）的化合物与式（III）的化合物反应：其中R.sup.8，R.sup.9和R.sup.10相同或不同，每个代表具有1至4个碳原子的烷基或苯基。其中，式（II）为：##STR2##式（III）为：##STR3##