(R)-4-benzyl-3-(5-bromopentanoyl)oxazolidine-2-one | 146232-49-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (R)-4-benzyl-3-(5-bromopentanoyl)oxazolidine-2-one
• 英文别名: (4R)-4-benzyl-3-(5-bromopentanoyl)-1,3-oxazolidin-2-one
• CAS: 146232-49-7
• 化学式: C₁₅H₁₈BrNO₃
• 分子量: 340.217
• InChiKey: LRQYSKNJBAVITI-CYBMUJFWSA-N

物化性质

• 沸点：
  478.7±28.0 °C(Predicted)
• 密度：
  1.420±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-4-benzyl-3-(5-bromopentanoyl)oxazolidine-2-one 在 lithium hydroxide 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 6.5h， 生成 (3R)-N¹-(2,4-dinitrophenyl)hexahydropyridazine-3-carboxylic acid
  参考文献：
  名称：

  阿奇霉素的合成研究。1.（3R）-和（3S）-哌嗪酸的高效不对称合成

  摘要：

  已经开发了一种方便的不对称合成（3R）-和（3S）-哌嗪酸的方法，该方法基于手性溴丙二酰羧酰亚胺烯醇酸酯与偶氮二叔丁基二羧酸叔丁酯的亲电子酰化作用，随后分子内S N 2置换溴化后得到的取代的氮杂阴离子。该方法的非对映选择性通常大于96％。

  DOI：

  10.1016/s0040-4039(00)60838-9
• 作为产物：
  描述：

  5-溴戊酸 在 正丁基锂 、 氯化亚砜 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 (R)-4-benzyl-3-(5-bromopentanoyl)oxazolidine-2-one
  参考文献：
  名称：

  Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis

  摘要：

  Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized beta(2)-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.

  DOI：

  10.1021/jm301346z

文献信息

• Synthesis of the Bioherbicidal Fungus Metabolite Macrocidin A
  作者：Robert G. Haase、Rainer Schobert

  DOI：10.1021/acs.orglett.6b03240

  日期：2016.12.16

  The second total synthesis of macrocidin A afforded the bioherbicidal fungal metabolite in 16 steps starting from doubly protected l-tyrosine. The 3-octanoyl side chain with the α-methyl group and an ω-bromo epoxide already in place was attached to the tetramic acid via a Yoshii–Yoda acylation, and the macrocycle was eventually closed in 55% yield by a Williamson etherification between the phenolate

  从双重保护的1-酪氨酸开始，大环蛋白A的第二次全合成以16个步骤提供了生物除草真菌的代谢产物。带有α-甲基和ω-溴环氧化物的3-辛酰基侧链通过Yoshii-Yoda酰化作用连接到四酸上，大环最终通过在两者之间的Williamson醚化反应以55％的收率封闭。酚盐和环氧溴化物。
• Enantioselective synthesis of (3R)- and (3S)-piperazic acids. The comparative unimportance of DMPU mediated retro-hydrazination
  作者：Karl J Hale、Jiaqiang Cai、Vern Delisser、Soraya Manaviazar、S.Andrew Peak、Gurpreet S Bhatia、Timothy C Collins、Neha Jogiya

  DOI：10.1016/0040-4020(95)00938-8

  日期：1996.1

  and Manaviazar (1992) on the asymmetric synthesis of (3R)- and (3S)-piperazic acids has been reinvestigated, and the originally claimed product yields fully substantiated. The claims made in reference 13 about the proportions of cyclised product 6 and starting bromide 20 isolated from the low temperature electrophilic hydrazination-nucleophilic cyclisation of 20 with di-t-butylazodicarboxylate (DBAD)

  为了回应Decicco和Leathers的最新文献报告（参考文献13），Hale，Delisser和Manaviazar（1992）关于（3 R）-和（3 S）-哌嗪酸的不对称合成的工作已被重新研究。 ，并且最初要求保护的产品的产量得到了充分证实。参考文献13约环化产物的比例制得的权利要求6和起始溴化物20从低温电hydrazination亲核环化分离20与二吨偶氮二羧酸丁酯（DBAD）和DMPU作为添加剂不准确。他们证明，当将DMPU加入到肼化反应混合物中时，逆酰肼化反应是有问题的，已经证明对环化产物的收率没有严重的不利影响并且是不重要的。参考文献13的另一主要主张是，当使用n -Bu 4 NI代替添加剂（代替DMPU）时，20的亲电肼化和亲核环化产生91％的分离产率中的6，这也是错误的。我们仔细地重复了按比例缩小版本的n -Bu 4 NI催化程序（参考资料13），发现经快速色谱分离后，
• Total Synthesis of NW-G01, a Cyclic Hexapeptide Antibiotic, and 34-epi-NW-G01
  作者：Setsuya Shibahara、Takaaki Matsubara、Keisuke Takahashi、Jun Ishihara、Susumi Hatakeyama

  DOI：10.1021/ol201912w

  日期：2011.9.2

  NW-G01, a cyclic hezapeptide antibiotic, and 34-epi-NW-G01 were synthesized by the highly stereoselective convergent approach for the first time, thereby unambiguously determining the absolute structure of NW-G01.
• [EN] PROCESS FOR THE PREPARATION OF (3R)- AND (3S)-PIPERAZIC ACID DERIVATIVES<br/>[FR] PROCEDE DE PREPARATION DES DERIVES DES ACIDES (3R)- et (3S)-PIPERAZIQUES
  申请人：UNIVERSITY COLLEGE LONDON

  公开号：WO1994011353A1

  公开（公告）日：1994-05-26

  (EN) A process of preparing a piperazic acid derivative of formula (1) wherein R represents an amino, hydroxyl or thiol group or an organic group as defined below and each of A and B represents a hydrogen atom or a non-interfering substituent, A and B being separate or joined directly together, so that together with the nitrogen atoms shown they form a fused ring group, in the form of a free base or an acid addition salt, the said process comprising: (a) reacting a valeric acid derivative of formula (3) wherein R represents an amino, hydroxyl or thiol group protected to prevent self-cyclisation of the valeric acid derivative into a lactam, lactone or thiolactone respectively, or an organic group which is not cleavable from the rest of the molecule in this reaction step and L represents a leaving group which is displaceable in the cyclisation step defined below, with a strong base under enolisation conditions to produce an enolate; (b) hydrazinating the enolate with a diazo compound of formula (5) wherein A and B are as defined above; (c) cyclising the product of the hydrazination; (d) optionally cleaving the R group from the cyclised product; and (e) optionally replacing the A and B substituents by hydrogen atoms, said steps (d) and (e) being carried out in either order or simultaneously.(FR) L'invention concerne un procédé de préparation des dérivés de l'acide pipérazique de la formule (1). Dans cette formule, R représente un groupe amino, hydroxyle ou thiol, ou un groupe organique comme défini ci-dessous et chacun d'entre A et B représente un atome d'hydrogène ou un substituant qui n'interfère pas, A et B sont séparés ou réunis ensemble directement en formant avec les atomes d'azote un cycle appartenant à un système de cycles condensés. Ces dérivés sont obtenus sous la forme de base libre ou d'un sel d'addition avec un acide. Le procédé en question consiste: (a) à faire réagir un dérivé de l'acide valérique de la formule (3) (dans laquelle R représente un groupe amino, hydroxyle ou thiol, protégés pour empêcher la cyclisation interne de l'acide valérique respectivement en lactame, lactone ou thiolactone ou encore un acide organique que l'on ne peut pas détacher du reste de la molécule dans cette étape de réaction et L représente un groupe partant qui est éliminé dans l'étape de cyclisation définie ci-dessus), avec une forte base dans des conditions d'énolisation pour produire un énolate; (b) à former un dérivé hydrazinique de l'énolate par réaction avec un composé diazo de la formule (5) dans laquelle A et B sont tels que définis ci-dessus; c) à effectuer une cyclisation du produit de l'hydrazination de l'étape précédente; d) éventuellement, à effectuer un clivage du groupe R du produit cyclisé; et e) éventuellement à remplacer les substituants A et B par des atomes d'hydrogène, les étapes (d) et (e) étant effectuées dans n'importe quel ordre ou simultanément.
• Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis
  作者：Markus Nahrwold、Christine Weiß、Tobias Bogner、Felix Mertink、Jens Conradi、Benedikt Sammet、Ralf Palmisano、Soledad Royo Gracia、Thomas Preuße、Norbert Sewald

  DOI：10.1021/jm301346z

  日期：2013.3.14

  Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized beta(2)-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.