benzyl (4S,5R)-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate | 171563-10-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl (4S,5R)-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate
• 英文别名: (4S,5R)-4-carboxybenzyl-5-methyloxazolidin-2-one；H-L-Oxd-OBn；L-Oxd-OBn；trans-L-5-methyl-2-oxo-oxazolidine-4-carboxylic acid benzyl ester
• CAS: 171563-10-3
• 化学式: C₁₂H₁₃NO₄
• 分子量: 235.24
• InChiKey: YIKNXYPXMYXRCF-SCZZXKLOSA-N

物化性质

• 沸点：
  444.0±34.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (4S,5R)-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate 在 palladium on activated charcoal 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 2.5h， 生成 (4S,5R)-3-(2-tert-Butoxycarbonylamino-2-methyl-propionyl)-5-methyl-2-oxo-oxazolidine-4-carboxylic acid
  参考文献：
  名称：

  Oxazolidin-2-one-Containing Pseudopeptides That Fold into β-Bend Ribbon Spirals

  摘要：

  Three sets of oligomers containing the 4-carboxy-5-methyloxazolidin-2-one (Oxd) moiety have been synthesized with the aim of checking whether these molecules are able to fold in ordered structures: A set [Boc-(L-Ala-L-Oxd),-OR], B set [BOC-(L-Ala-D-Oxd)(n)-OR], and C set [Boc-(Aib-L-Oxd)(n)-OR] preferential conformations have been analyzed with IR absorption, NMR, and CID. We have noticed that in these oligomers three stabilizing effects are active: (i) the rigid Oxd -CO-N(CH <)-CO- moiety, which always tend to assume a trans conformation; (ii) the formation of Oxd C=(OH)-H-...-C-alpha intramolecolar H-bonds; (iii) the alternate formation of 1 - 4 intramolecular C=(OH)-H-...-N H-bonds. Through the analysis of the experimental data, we could demonstrate that only the oligomers of the B set are able to meet all three requirements listed above. By a deeper insight into the CD spectra, we gathered that the secondary structure adopted by the B set oligomers is a beta-bend ribbon spiral, which is a subtype of the 3(10)-helix.

  DOI：

  10.1021/ja056762h
• 作为产物：
  描述：

  (2S,3R)-N-Boc-2-carboxybenzyl-3-methylaziridine 在 tin(II) trifluoromethanesulfonate 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以90%的产率得到benzyl (4S,5R)-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate
  参考文献：
  名称：

  合成反式（4S，5R）-4-羧基苄基5-甲基恶唑烷丁-2-酮的低聚物：一种新的折叠剂的方法。

  摘要：

  描述了分别含有反式-（4S，5R）-4-羧基5-甲基恶唑烷-2-酮的三个和四个残基的两个低聚物的合成。通过从苄基-N-Boc-（3R）-氨基丁酸酯开始，通过环化成相应的反-（2S，3R）-2-羧基苄基-3-甲基-N-Boc-氮丙啶和产物的重排获得单体。 Sn（OTf）2催化合成反式-（4S，5R）-4-羧基苄基-5-甲基恶唑烷丁-2-酮。通过活化羧基作为其五氟苯基酯来合成低聚物。三聚体和四聚体的收率很高，它们的1 H NMR光谱表明这些分子以有序结构折叠，其中一个环的C-4氢始终靠近下一个环的羰基。

  DOI：

  10.1021/jo005583+

文献信息

• Conformational studies on a medium size cyclopseudopeptide containing the oxazolidin-2-one moiety
  作者：Gaetano Angelici、Nicola Castellucci、Claudia Tomasini

  DOI：10.1002/poc.2977

  日期：2012.11

  yield. The cycle contains four units, all formed by an α‐amino acid (Xaa) and a 4‐carboxy‐5‐methyl‐oxazolidin‐2‐one group (4‐carboxy‐5‐methyl‐oxazolidin‐2‐one = Oxd) in the same configuration ( l or d). In the final sequence, the four ll or dd units are alternated so that, after cyclization, cyclo‐( l‐Xaa‐ l‐Oxd‐ d‐Xaa‐ d‐Oxd‐ l‐Xaa‐ l‐Oxd‐ d‐Xaa‐ d‐Oxd) is formed. The conformational analysis of this

  据报道，在溶液中有效合成了24个假肽元环。该循环包含四个单元，全部由一个α-氨基酸（Xaa）和一个4-羧基-5-甲基-恶唑烷二-2-基团组成（4-羧基-5-甲基-恶唑烷-2-2-1 = Oxd）在相同的配置（l或d）中。在最后的序列中，四个ll或dd单位是交替的，因此在环化后，环-（l -Xaa- l -Oxd- d -Xaa- d -Oxd- l -Xaa- l -Oxd- d -Xaa- d-Oxd）形成。已通过红外和1  H NMR光谱对该化合物进行了构象分析，结果表明，α-氨基酸的CHα氢保留了游离前体光谱中记录的非常隐蔽的化学位移。此外，NH氢具有形成交叉峰的趋势，因此表明该循环位于能够容纳小分子的大圆圈内，因此该化合物是药物递送研究的有希望的候选者。版权所有©2012 John Wiley＆Sons，Ltd.
• Solid-State Properties and Vibrational Circular Dichroism Spectroscopy in Solution of Hybrid Foldamers Stereoisomeric Mixtures
  作者：Nicola Castellucci、Giuseppe Falini、Lorenzo Milli、Magda Monari、Sergio Abbate、Giovanna Longhi、Ettore Castiglioni、Giuseppe Mazzeo、Claudia Tomasini

  DOI：10.1002/cplu.201300306

  日期：2014.1

  Boc-(L-Phe-D-Oxd)2 -OBn (3). The preferred conformation of 1 ranges from a polyproline II (PPII) helix to β strands and we can gather that longer and more structured oligomers will form PPII helices. In contrast, compound 3 forms infinite antiparallel β-sheet structures; thus showing the strong effect of the reversal of the absolute configuration of the Oxd moieties on the secondary structure of these hybrid

  在缓慢蒸发Boc-（L-Phe-L-Oxd）2-OBn的1：1非对映异构混合物时（1; Boc =叔丁氧羰基; L-Oxd =反式-（4S，5R）-4-羧基5 -甲基恶唑烷丁-2-酮（Bn =苄氧羰基）和Boc-L-Phe-L-Oxd-D-Phe-L-Oxd-OBn（2）在甲基叔丁基醚中，适用于X射线衍射的单晶研究获得。相反，两种纯的低聚物在任何结晶条件下均导致形成无定形固体。在固相中充分阐明了两种低聚物的优先构象，并与Boc-（L-Phe-D-Oxd）2-OBn的已知构象进行了比较（3）。1的优选构象范围是从聚脯氨酸II（PPII）螺旋到β链，我们可以收集到更长，更结构化的低聚物将形成PPII螺旋​​。相反，化合物3形成无限的反平行β-折叠结构；因此显示出Oxd部分的绝对构型的逆转对这些杂合折叠子的二级结构的强烈影响。振动圆二色性分析表明，溶液中保留了相同的结果。最终，我们证明了1和2的
• Pseudopeptide Foldamers − The Homo-Oligomers of Benzyl (4S,5R)-5-Methyl-2-oxo-1,3-oxazolidine-4-carboxylate
  作者：Claudia Tomasini、Valerio Trigari、Simone Lucarini、Fernando Bernardi、Marco Garavelli、Cristina Peggion、Fernando Formaggio、Claudio Toniolo

  DOI：10.1002/ejoc.200390027

  日期：2003.1

  construction of pseudopeptide foldamers. IR, 1H NMR and CD techniques, implemented by detailed DFT computational modeling, were exploited to investigate the preferred three-dimensional structure of benzyl (4S,5R)-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate homo-oligomers synthesized to the pentamer level. The resulting poly(L-Pro)n II like helical conformation was found to be stabilized by intramolecular α-C−H···O=C

  2-oxo-1,3-oxazolidine-4-羧酸被设计为一种新的、构象受限的构建块，用于构建假肽折叠体。通过详细的 DFT 计算模型实施的 IR、1H NMR 和 CD 技术被用来研究苄基 (4S,5R)-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate 的首选三维结构合成到五聚体水平的均聚物。发现所得的聚(L-Pro)n II类螺旋构象通过分子内α-C-H···O=C氢键稳定。这种新颖的、基于酰基氨基甲酸酯的三元折叠结构，如果经过适当的功能化，有望成为各种应用的强大模板。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
• Development of new calcium receptors based on oxazolidin-2-ones containing pseudopeptides
  作者：Gianluigi Luppi、Andrea Garelli、Luca Prodi、Quirinus B. Broxterman、Bernard Kaptein、Claudia Tomasini

  DOI：10.1039/b501017a

  日期：——

  With the aim of designing a new calcium receptor, the synthesis and the conformational analysis of a small library of dipeptides having the general formula Ac–Oxx–L-Xaa–OBn [Oxx = L-Oxd, (4S,5R)-4-methyl-5-carboxyoxazolidin-2-one; D-Oxd, (4R,5S)-4-methyl-5-carboxyoxazolidin-2-one; or D-Oxac (4R)-(2-oxo-1,3-oxazolidin-4-yl)-acetic acid] is reported. Ac–L-Oxd–L-Ala–OBn was identified as the most promising compound by MS–ESI analysis and this outcome was confirmed by photoluminescence spectroscopy.

  为了设计一种新的钙受体，报道了一小组二肽的合成及其构象分析，具有一般式 Ac–Oxx–L-Xaa–OBn [Oxx = L-Oxd, (4S,5R)-4-甲基-5-羧基噁唑烷-2-酮；D-Oxd, (4R,5S)-4-甲基-5-羧基噁唑烷-2-酮；或D-Oxac (4R)-(2-氧-1,3-噁唑烷-4-基)-乙酸]。通过质谱-电喷雾离子化分析，识别出 Ac–L-Oxd–L-Ala–OBn 是最有前景的化合物，这一结果通过光致发光光谱得到了确认。
• Development and Conformational Analysis of a Pseudoproline-Containing Turn Mimic
  作者：Gianluigi Luppi、Donato Lanci、Valerio Trigari、Marco Garavelli、Andrea Garelli、Claudia Tomasini

  DOI：10.1021/jo026233l

  日期：2003.3.1

  The liquid-phase synthesis and the conformational analysis of a small library of fully protected tetramers containing L-pyroglutamic acid (L-pGlu), (4S,5R)-4-methyl-5-carboxybenzyloxazolidin-2-one (L-Oxd), or (4R,5S)-4-methyl-5-carboxybenzyloxazolidin-2-one (D-Oxd) as residue i + 1 are reported to test the tendency of these oligomers to assume beta-hairpin conformation. The most promising molecule is BOC-L-Val-D-Oxd-Gly-L-Ala-OBn, which assumes a preferential beta-turn conformation in CDCl3, as shown by IR and H-1 NMR analysis. These findings have been confirmed by DFT calculations, which provide an interpretation for the available experimental data and agree with the reported observations.