(4R)-hydroxypyrrolidine-1,(2S)-dicarboxylic acid 2-allyl ester 1-tert-butyl ester | 186320-37-6

• 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: (4R)-hydroxypyrrolidine-1,(2S)-dicarboxylic acid 2-allyl ester 1-tert-butyl ester
• 英文别名: trans-N-tert-butoxycarbonyl-4-hydroxy-L-proline allyl ester；Boc-Hyp-OAll；(2S,4R)-2-Allyloxycarbonyl-1-tert-butoxycarbonyl-4-hydroxy-pyrrolidine；1-O-tert-butyl 2-O-prop-2-enyl (2S,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate
• CAS: 186320-37-6
• 化学式: C₁₃H₂₁NO₅
• 分子量: 271.313
• InChiKey: LYISHKMQHWCNTB-ZJUUUORDSA-N

物化性质

• 沸点：
  374.6±42.0 °C(Predicted)
• 密度：
  1.181±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R)-hydroxypyrrolidine-1,(2S)-dicarboxylic acid 2-allyl ester 1-tert-butyl ester 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 (2S,4S)-1-[(2-methylpropan-2-yl)oxycarbonyl]-4-sulfanylpyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  天然化学连接中肽基脯氨酰硫酯的内部活化

  摘要：

  与丙氨酰硫酯相比，脯氨酰硫酯在天然化学连接 (NCL) 中显示出显着较低的反应性。本报告描述了 NCL 中肽基脯氨酰硫酯的温和有效的内部活化方案，不使用任何基于硫醇的添加剂，其中在 C 端脯氨酸上引入 4-硫醇取代基显着提高了脯氨酰硫酯的反应性，通过形成双环硫内酯中间体。动力学数据表明反应速率与丙氨酰硫酯的报道数据相当，机理研究表明两个肽段的连接是通过 NCL 样途径而不是直接氨解进行的，这确保了化学选择性和各种氨基酸侧链的相容性。这种基于 4-巯基硫酯的协议还允许高效的一锅连接脱硫程序。该方法的效用已在 Wilms 肿瘤蛋白 1 的富含脯氨酸区域的合成中得到进一步证明。

  DOI：

  10.1021/jacs.6b01202
• 作为产物：
  描述：

  L-羟基脯氨酸 在 吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (4R)-hydroxypyrrolidine-1,(2S)-dicarboxylic acid 2-allyl ester 1-tert-butyl ester
  参考文献：
  名称：

  由5-O-（2-吡啶羰基）-L-阿拉伯呋喃糖基三氯乙酰亚胺酸酯进行的β-L-阿拉伯呋喃糖基化反应。

  摘要：

  我们通过使用5-O-（2-吡啶羰基）-L-阿拉伯呋喃糖基三氯乙酰亚氨酸酯10作为供体来描述β-L-阿拉伯呋喃糖基化方法。该方法允许使用广泛的受体底物，尤其是氨基酸受体。通过该方法容易地实现β-（1，4）-L-阿拉伯呋喃糖基-（2S，4R）-4-羟基-L-脯氨酸（β-L-Araf-L-Hyp4）及其二聚体的立体选择性合成。立体选择性和反应产率均优异。为了证明该方法的实用性，以一锅法方式制备了三糖。

  DOI：

  10.1016/j.carres.2018.02.006

文献信息

• Dual Catalytic Decarboxylative Allylations of α-Amino Acids and Their Divergent Mechanisms
  作者：Simon B. Lang、Kathryn M. O'Nele、Justin T. Douglas、Jon A. Tunge

  DOI：10.1002/chem.201503644

  日期：2015.12.14

  The room temperature radical decarboxylative allylation of N‐protected α‐amino acids and esters has been accomplished via a combination of palladium and photoredox catalysis to provide homoallylic amines. Mechanistic investigations revealed that the stability of the α‐amino radical, which is formed by decarboxylation, dictates the predominant reaction pathway between competing mechanisms.

  N保护的α-氨基酸和酯在室温下进行自由基脱羧烯丙基化反应，是通过钯和光氧化还原催化作用的组合来实现的，以提供均胺基胺。机理研究表明，由脱羧作用形成的α-氨基自由基的稳定性决定了竞争机制之间的主要反应途径。
• Antibiotic oxazolidinone derivatives
  申请人：Syngenta Limited

  公开号：US06605630B1

  公开（公告）日：2003-08-12

  The invention concerns a compound of the formula (I): wherein, for example: T is of the formula (IA), (IB), or (IC); R1 is of the formula —NHC(═O)Rb wherein Rb is (1-4C)alkyl; R2 and R3 are hydrogen or fluoro; >A—B— is >C═CH— (but not when T is (IA)) or >CH—CH2—; wherein when T is of the formula (IA) or (IB); R6 is, for example, (1-4C)alkyl; R5 is hydrogen, R10CO—, R10SO2— or R10CS— wherein R10 is, for example, optionally substituted phenyl, or (1-10C)alkyl, or when T is of the formula (IA), (IB); or (IC): R5 and R6 are linked to give a 5- or 6-membered ring which is fused to the ring shown in (IA), (IB), or (IC) so as to give an optionally substituted bicyclic ring; and pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them, and their use as antibacterial agents.

  这项发明涉及以下式(I)的化合物：其中，例如：T的式为(IA)、(IB)或(IC)；R1的式为—NHC(═O)Rb，其中Rb为(1-4C)烷基；R2和R3为氢或氟；>A—B—为>C═CH—（但当T为(IA)时除外）或>CH—CH2—；其中当T为(IA)或(IB)的式时；R6为，例如，(1-4C)烷基；R5为氢、R10CO—、R10SO2—或R10CS—，其中R10为，例如，可选择地取代的苯基，或(1-10C)烷基，或当T为(IA)、(IB)或(IC)的式时：R5和R6相连形成与(IA)、(IB)或(IC)中所示环融合的5-或6-成员环，从而形成可选择地取代的双环环，并且其药学上可接受的盐，其制备方法，含有它们的药物组合物，以及它们作为抗菌剂的用途。
• Synthesis of Oligomers of β-<scp>l</scp>-Arabinofuranosides of (4<i>R</i>)-4-Hydroxy-<scp>l</scp>-proline Relevant to the Mugwort Pollen Allergen, Art v 1
  作者：Ning Xie、Carol M. Taylor

  DOI：10.1021/jo501191b

  日期：2014.8.15

  An efficient, convergent solution phase synthesis of monomer, dimer, trimer and tetramer of the β-l-arabinofuranosylated hydroxyproline (β-l-Araf-Hyp) glycocluster is described. This motif constitutes the carbohydrate-specific epitope of Art v 1, the major allergen of mugwort pollen. While a single monomeric unit was proposed at the outset, poor yields for the seemingly trivial steps of end-capping

  单体，二聚体，三聚体和四的β-的一种高效，融合的解决方案相合成升-arabinofuranosylated羟脯氨酸（β-升-Ara ˚F -Hyp）glycocluster进行说明。该基序构成了艾蒿花粉的主要过敏原Art v 1的碳水化合物特定表位。虽然一开始就提出了一个单体单元，但似乎很不容易的封端以N端乙酰胺和C端甲基酰胺取代保护基的简单步骤导致引入N端，中央和C-取代。 β- l- Ara f -Hyp末端构建单元。二聚体2通过偶合两种单体，然后氢解苄基醚保护基，以60％的收率获得二氯乙烷。三聚体3是在35％的产率通过一个[2 + 1]耦合和四聚体获得的4 15经由收率％[2 + 2]片段缩合。圆二色光谱表明单体1个显示无组织结构，而化合物2 - 4显示了在200 nm和~220 MN弱阳性条带强负带，由于是聚脯氨酸II螺旋的特征。
• Potent and Fully Noncompetitive Peptidomimetic Inhibitor of Multidrug Resistance P-Glycoprotein
  作者：Ophélie Arnaud、Ali Koubeissi、Laurent Ettouati、Raphaël Terreux、Ghina Alamé、Catherine Grenot、Charles Dumontet、Attilio Di Pietro、Joëlle Paris、Pierre Falson

  DOI：10.1021/jm100839w

  日期：2010.9.23

  N-alpha-Boc-L-Asp(OBn)-L-Lys(Z)-OtBu (reversin 121, I), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-L-proline (4(R)Hyp) gave compounds 11 and 15 characterized by half-maximal inhibitory concentrations (1050) of 0.6 and 0.2 mu M, which are 2- and 7-fold lower than that of the parent molecule. The difference in IC50 between 11 and 15 rests on the carbonyl group of the peptidyl bond, reduced in 15. Those compounds are rather specific of P-gp, having no or limited activity on MRP1 and BCRP. 15 displayed no marked cytotoxicity up to 10-fold its IC50. Importantly, 15 equally inhibited the Hoechst 33342 and daunorubicin effluxes through a typical noncompetitive inhibition mechanism, suggesting its binding to a site different from the and R drug-transport sites.
• Synthesis of a Dimer of β-(1,4)-<scp>l</scp>-Arabinosyl-(2<i>S</i>,4<i>R</i>)-4-hydroxyproline Inspired by Art v 1, the Major Allergen of Mugwort
  作者：Ning Xie、Carol M. Taylor

  DOI：10.1021/ol102112z

  日期：2010.11.5

  N alpha-tert-Butoxycarbonyl-L-trans-4-hydroxyproline allyl ester (Boc-Hyp-OAII) was glycosylated with 2,3,5-tri-O-benzyl-L-arabinose p-cresylthioglycoside in 60% yield with 4:1 beta:alpha stereoselectivity. Deprotection of N- and C-terminii independently gave a prolyl amine and prolyl carboxylate respectively that were coupled under standard conditions with 1-[bis-(dimethylamino)methylene]-1H-1,2,3-triazolo-[4,5,b]-pyridininium hexafluorophosphate 3-oxide (N-HATU) to give the dimer 1 in 46% yield. These results represent the first steps toward the production of homogeneous oligomers to determine the minimal epitope of the Art v 1 allergen.