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 | 105318-41-0

• 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 (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-phenylthio-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• 英文别名: (4-nitrophenyl)methyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-phenylsulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• CAS: 105318-41-0
• 化学式: C₂₃H₂₂N₂O₆S
• 分子量: 454.503
• InChiKey: KNKUCZARQBAVDD-TWKYDXJASA-N

物化性质

• 熔点：
  149-153 °C
• 沸点：
  658.9±55.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  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 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 phosphate buffer 为溶剂， 生成 sodium;(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-phenylsulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
  参考文献：
  名称：

  Synthesis and Structure-activity Relationships of a Novel Oral Carbapenem, CS-834.

  摘要：

  我们研究了一种碳青霉烯酯类前药，旨在开发一种强效的口服活性β-内酰胺抗生素。合成了一系列1β-甲基碳青霉烯衍生物。我们发现，一些在C-2侧链中含有酰胺基团的衍生物显示出强大的且平衡的抗菌活性，并且对脱氨�酶-I具有高稳定性。通过修饰C-3酯的前体部分，优化了衍生物的口服吸收。Pivaloyloxymethyl (1R, 5S, 6S)-6-[(R)-1-羟基乙基]-1-甲基-2-[(R)-5-氧代吡咯烷-3-基硫]-1-碳青霉烯-2-em-3-羧酸酯，CS-834，已被选为最具前景的化合物进行进一步评估。

  DOI：

  10.7164/antibiotics.50.429
• 作为产物：
  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

文献信息

• Synthesis and Structure-activity Relationships of a Novel Oral Carbapenem, CS-834.
  作者：MASAO MIYAUCHI、ROKURO ENDO、MASAFUMI HISAOKA、HIROSHI YASUDA、ISAO KAWAMOTO

  DOI：10.7164/antibiotics.50.429

  日期：——

  We have studied an ester prodrug of a carbapenem to develop a potent orally active β-lactam antibiotic. A variety of 1β-methylcarbapenem derivatives have been synthesized. We have found that some derivatives having an amide group in the C-2 side chain show potent and well balanced antibacterial activities as well as high stability against dehydropeptidase-I. Oral absorption of derivatives has been optimized by modifying the C-3 ester promoiety. Pivaloyloxymethyl (1R, 5S, 6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[(R)-5-oxopyrrolidin-3-ylthio]-1-carbapen-2-em-3-carboxylate, CS-834, has been selected as the most promising compound for further evaluation.

  我们研究了一种碳青霉烯酯类前药，旨在开发一种强效的口服活性β-内酰胺抗生素。合成了一系列1β-甲基碳青霉烯衍生物。我们发现，一些在C-2侧链中含有酰胺基团的衍生物显示出强大的且平衡的抗菌活性，并且对脱氨�酶-I具有高稳定性。通过修饰C-3酯的前体部分，优化了衍生物的口服吸收。Pivaloyloxymethyl (1R, 5S, 6S)-6-[(R)-1-羟基乙基]-1-甲基-2-[(R)-5-氧代吡咯烷-3-基硫]-1-碳青霉烯-2-em-3-羧酸酯，CS-834，已被选为最具前景的化合物进行进一步评估。
• Efficient Method for the Deprotection of <i>tert</i>-Butyldimethylsilyl Ethers with TiCl₄−Lewis Base Complexes:  Application to the Synthesis of 1β-Methylcarbapenems
  作者：Akira Iida、Hiroki Okazaki、Tomonori Misaki、Makoto Sunagawa、Akira Sasaki、Yoo Tanabe

  DOI：10.1021/jo0604484

  日期：2006.7.1

  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'.