p-nitrobenzyl (5R,6S)-2-diphenoxy phosphoryloxy-6-[(R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate | 77171-49-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: p-nitrobenzyl (5R,6S)-2-diphenoxy phosphoryloxy-6-[(R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate
• 英文别名: p-Nitrobenzyl (5R,6S)-2-(diphenylphosphoryloxy)-6-((1R)-1-hydroxyethyl)carbapen-2-em-3-carboxylate；(4-nitrophenyl)methyl (5R,6S)-3-diphenoxyphosphoryloxy-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• CAS: 77171-49-4
• 化学式: C₂₈H₂₅N₂O₁₀P
• mdl: MFCD08706413
• 分子量: 580.488
• InChiKey: VVLXPESSYNCTFQ-DVKBMCPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.214
• 拓扑面积：
  157
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  p-nitrobenzyl (5R,6S)-2-diphenoxy phosphoryloxy-6-[(R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate 生成 (4-nitrophenyl)methyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-(1,3-thiazol-2-ylmethylsulfanyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
  参考文献：
  名称：

  KIM, CHOUNG U.

  摘要：

  DOI：
• 作为产物：
  描述：

  4-乙酰氧基氮杂环丁酮 在 盐酸 、 甲醇 、 4-二甲氨基吡啶 、 dirhodium tetraacetate 、 N,N-二异丙基乙胺 、 zinc(II) chloride 作用下， 以 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 生成 p-nitrobenzyl (5R,6S)-2-diphenoxy phosphoryloxy-6-[(R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate
  参考文献：
  名称：

  碳青霉烯类的催化不对称途径

  摘要：

  据报道，N-乙酰基硫霉素和表硫霉素 A 以其易于脱保护的形式高效合成，其中三个连续的立体中心在单个催化不对称氮杂环丁酮形成反应中建立。这些例子是合成 C-5/C-6顺式或反式碳青霉烯类的模板，独立控制 C-8 立体中心。已制备了各种天然碳青霉烯和潜在生物合成中间体的氧化和立体化学定义的氮杂环丁酮前体库，以促进碳青霉烯抗生素生物合成的研究。

  DOI：

  10.1021/ol901269d

文献信息

• Synthesis and Structure-activity Relationships of 1.BETA.-Methylcarbapenems with Quaternary Ammonium Side Chains.
  作者：KATSUYA ISHIKAWA、KATSUHIKO KOJIMA、MASAO MIYAUCHI、ROKURO ENDO、HIROSHI YASUDA、ISAO KAWAMOTO

  DOI：10.7164/antibiotics.51.757

  日期：——

  potent and well balanced antibacterial activity as well as high stability against dehydropeptidase-I. The in vivo potency of these two carbapenems was compared with that of meropenem. The structure-activity relationships leading to these carbapenems are also described.

  研究了在C-2位带有季铵基的1β-甲基卡巴姆的合成和抗菌活性。已经合成了两种类型的新碳青霉烯衍生物。这些1β-甲基卡巴ene，一种具有（2S，4S）-2- [1，1-二甲基-2-（1-哌嗪基）羰基]吡咯烷二-4-+++基硫基，另一种具有（2S）。 ，4S）-2-（4-氨基甲酰基甲基-4-甲基高哌嗪并-1-基羰基）吡咯烷-4-基硫基显示出有效且均衡的抗菌活性，并且对脱氢肽酶-I具有很高的稳定性。将这两种碳青霉烯与美罗培南的体内效价进行了比较。还描述了导致这些碳青霉烯类的构效关系。
• 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。
• 2-(substituted pyrrolidinylthio)carbapenem derivatives
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US05374720A1

  公开（公告）日：1994-12-20

  A compound of the formula: ##STR1## wherein R is a hydrogen atom or a methyl group, R.sup.1 is a hydrogen atom or a negative charge, each of R.sup.2 and R.sup.3 which may be the same or different, is a hydrogen atom, a lower alkyl group, a hydroxy lower alkyl group, a formimidoyl group, an acetoimidoyl group, --COOR.sup.4, --CON(R.sup.5)R.sup.6, --N(R.sup.5)R.sup.6, --CH.sub.2 COOR.sup.4, --CH.sub.2 N(R.sup.5)R.sup.6 or --CH.sub.2 CON(R.sup.5)R.sup.6 (wherein R.sup.4 is a hydrogen atom or a lower alkyl group, each of R.sup.5 and R.sup.6 which may be the same or different, is a hydrogen atom or a lower alkyl group, or R.sup.5 and R.sup.6 form together with the adjacent nitrogen atom a heterocyclic group selected from the group consisting of an aziridinyl group, an azetidinyl group, a pyrrolidinyl group and a piperidyl group), A is .dbd.NR.sup.7, .dbd.N.sup.+ (R.sup.7)R.sup.8, wherein each of R.sup.7 and R.sup.8 which may be the same or different, is a hydrogen atom, a lower alkyl group, a hydroxy lower alkyl group, a formimidoyl group, an acetoimidoyl group, --COOR.sup.4, --CON(R.sup.5)R.sup.6, --N(R.sup.5)R.sup.6, --CH.sub.2 COOR.sup.4, --CH.sub.2 N(R.sup.5)R.sup.6 or --CH.sub.2 CON(R.sup.5)R.sup.6 (wherein R.sup.4, R.sup.5 and R.sup.6 are as defined above), p is an integer of from 0 to 3, and q is an integer of from 1 to 3; or a pharmaceutically acceptable salt or ester thereof.

  该化合物的公式为：##STR1##，其中R是氢原子或甲基基团，R.sup.1是氢原子或负电荷，R.sup.2和R.sup.3可以是相同的或不同的，是氢原子、低级烷基团、羟基低级烷基团、甲酰亚胺基团、乙酰亚胺基团、--COOR.sup.4、--CON(R.sup.5)R.sup.6、--N(R.sup.5)R.sup.6、--CH.sub.2 COOR.sup.4、--CH.sub.2 N(R.sup.5)R.sup.6或--CH.sub.2 CON(R.sup.5)R.sup.6（其中R.sup.4是氢原子或低级烷基团，R.sup.5和R.sup.6可以是相同的或不同的，是氢原子或低级烷基团，或者R.sup.5和R.sup.6与相邻的氮原子共同形成一个杂环组，选自包括氮环丙烷基团、氮环丁烷基团、吡咯烷基团和哌啶基团在内的组中），A是.dbd.NR.sup.7，.dbd.N.sup.+ (R.sup.7)R.sup.8，其中R.sup.7和R.sup.8可以是相同的或不同的，是氢原子、低级烷基团、羟基低级烷基团、甲酰亚胺基团、乙酰亚胺基团、--COOR.sup.4、--CON(R.sup.5)R.sup.6、--N(R.sup.5)R.sup.6、--CH.sub.2 COOR.sup.4、--CH.sub.2 N(R.sup.5)R.sup.6或--CH.sub.2 CON(R.sup.5)R.sup.6（其中R.sup.4、R.sup.5和R.sup.6如上所述定义），p是从0到3的整数，q是从1到3的整数；或其药用可接受的盐或酯。
• Stereoselective Reactions. XX. Synthetic Studies on Optically Active .BETA.-Lactams. III. Stereocontrolled Synthesis of Chiral Intermediate to (+)-Thienamycin from D-Glucose.
  作者：Nobuo IKOTA、Osamu YOSHINO、Kenji KOGA

  DOI：10.1248/cpb.39.2201

  日期：——

  A chiral key intermediate (19a) for the synthesis of (+)-thienamycin was synthesized starting from D-glucose. The enol ether 13, obtained from the ketone 11 by Horner-Wittig reaction, was transformed to the corresponding methyl ester 16 by pyridinium chlorochromate oxidation or by employing the Wacker process. The ester 16 was further converted to the β-lactam 19a, which is a useful chiral precursor to (+)-thienamycin.

  以D-葡萄糖为起始原料，合成了用于合成(+)-硫霉素的立体关键中间体(19a)。通过Horner-Wittig反应从酮11获得的烯醇醚13，经吡啶氯铬酸氧化或采用Wacker工艺转化为相应的甲酯16。进一步将酯16转化为β-内酰胺19a，它是合成(+)-硫霉素的有用手性前体。
• A practical synthesis of (±)-thienamycin
  作者：D.G. Melillo、I. Shinkai、T. Liu、K. Ryan、M. Sletzinger

  DOI：10.1016/s0040-4039(00)78606-0

  日期：1980.1

  An efficient and operationally simple synthesis of (±)-thienamycin is described.

  描述了（±）-硫霉素的有效且操作简单的合成。