1-苄基2-甲基1,2-吡咯烷二羧酸酯 | 182210-00-0

• 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
• 中文名称: 1-苄基2-甲基1,2-吡咯烷二羧酸酯
• 英文名称: N-carbobenzyloxy-D-proline methyl ester
• 英文别名: (R)-N-benzyloxycarbonylproline methyl ester；Z-D-Pro-OMe；methyl (2R)-(benzyloxycarbonyl)pyrrolidine-2-carboxylate；methyl (R)-N-benzyloxycarbonylprolinate；benzyl 2-methyl (R-pyrrolidine)-1,2-dicarboxylate；(R)-N-benzyloxycarbonylmethylprolinate；(R)-1-Benzyl 2-methyl pyrrolidine-1,2-dicarboxylate；1-O-benzyl 2-O-methyl (2R)-pyrrolidine-1,2-dicarboxylate
• CAS: 182210-00-0
• 化学式: C₁₄H₁₇NO₄
• mdl: MFCD09954285
• 分子量: 263.293
• InChiKey: BLQYEDXWEDWCNJ-GFCCVEGCSA-N

物化性质

• 沸点：
  375.0±42.0 °C(Predicted)
• 密度：
  1.220±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-苄基2-甲基1,2-吡咯烷二羧酸酯 在 palladium dihydroxide WSC*HCl 、 氢气 、 1-羟基苯并三唑 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 41.0h， 生成 methyl (2R)-1-([(2S,4R)-4-tert-butoxy-1-(benzyloxycarbonyl)pyrrolidin-2-yl]carbonyl)pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Identification of a Novel 4-Aminomethylpiperidine Class of M₃ Muscarinic Receptor Antagonists and Structural Insight into Their M₃ Selectivity

  摘要：

  Identification of a novel class of potent and highly selective M-3 muscarinic antagonists is described. First, the structure-activity relationship in the cationic amine core of our previously reported triphenylpropionamide class of M-3 selective antagonists was explored by a small diamine library constructed in solid phase. This led to the identification of M-3 antagonists with a novel piperidine pharmacophore and significantly improved subtype selectivity from a previously reported class. Successive modification on the terminal triphenylpropionamide part of the newly identified class gave 14a as a potent M-3 selective antagonist that had > 100-fold selectivity versus the M-1, M-2, M-4, and M-5 receptors (M-3: K-i = 0.30 nM, M-1/M-3 = 570-fold, M-2/M-3 = 1600-fold, M-4/M-3 = 140-fold, M-5/M-3 = 12000-fold). The possible rationale for its extraordinarily higher subtype selectivity than reported M-3 antagonists was hypothesized by sequence alignment of multiple muscarinic receptors and a computational docking of 14a into transmembrane domains of M-3 receptors.

  DOI：

  10.1021/jm051205r
• 作为产物：
  描述：

  N-[苄氧羰基]-D-谷氨酸 1-甲基酯 在 N-甲基吗啉 、 sodium tetrahydroborate 、 四溴化碳 、 sodium hydride 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.38h， 生成 1-苄基2-甲基1,2-吡咯烷二羧酸酯
  参考文献：
  名称：

  制备光学活性保护脯氨酸的简便新方法

  摘要：

  用四氢呋喃 (THF) 中的氢化钠处理由受保护的 L-谷氨酸制备的 LN 保护的 2-氨基-5-溴戊酸酯，以高产率得到相应的保护 L-脯氨酸。另一方面，2-氨基丁酸衍生物与氢化钠反应得到1-氨基环丙烷-1-羧酸衍生物。

  DOI：

  10.1246/cl.1996.621

文献信息

• Synthesis and structure of prolinal-containing peptides, and their use as specific inhibitors of prolyl endopeptidases.
  作者：MAKOTO NISHIKATA、HIDEYOSHI YOKOSAWA、SHIN-ICHI ISHII

  DOI：10.1248/cpb.34.2931

  日期：——

  Peptide aldehydes are potent inhibitors of serine and cysteine proteases. In the present work, N-benzyloxycarbonyl (Z) dipeptides containing prolinal at the carboxyl terminus were syntheized as inhibitors of prolyl endopeptidases. Since no aldehyde proton was detected by proton nuclear magnetic resonance (1H-NMR) spectrometry, a cyclic structure was proposed for these peptides. Compounds with a Z-L-X-L-prolinal structure were strong inhibitors of prolyl endopeptidases from the ascidian, Halocynthia roretzi, and Flavobacterium meningosepticum. The potency was in the order of Z-L-Val-L-prolinal≃Z-L-Ile-L-prolinal>Z-L-Phe-L-prolinal>Z-L-Ala-L-prolinal with IC50 values of 10-8-10-6 M order for both enzymes. Conversion of the aldehyde into an alcohol or an acid moiety resulted in a considerable decrease in the inhibitory activity. The diastereomers of Z-L-Phe-L-prolinal were much less inhibitory. This result is not compatible with the reported stereospecifity of the Flavobacterium enzyme for its substrated [T. Yoshimoto, R. Walter and D. Tsuru, J. Biol. Chem., 255, 4786 (1980)]. This implies that the open species binds preferentially to the enzyme active site.

  肽醛是丝氨酸和半胱氨酸蛋白酶的强效抑制剂。在本研究工作中，合成了含羧基末端脯氨醛的N-苄氧羰基（Z）二肽，作为脯氨酰内肽酶的抑制剂。由于通过质子核磁共振（1H-NMR）光谱法未检测到醛质子，因此为这些肽提出了一个环状结构。具有Z-L-X-L-脯氨醛结构的化合物是海鞘Halocynthia roretzi和黄杆菌Flavobacterium meningosepticum的脯氨酰内肽酶的强效抑制剂。其效力顺序为Z-L-Val-L-脯氨醛≈Z-L-Ile-L-脯氨醛>Z-L-Phe-L-脯氨醛>Z-L-Ala-L-脯氨醛，IC50值为10-8-10-6 M，对两种酶均有效。将醛转化为醇或酸部分会导致抑制活性显著降低。Z-L-Phe-L-脯氨醛的差向异构体抑制作用较弱。这一结果与黄杆菌酶对其底物的报道立体特异性不一致。这表明开放型物种优先结合到酶活性位点。
• ORTHO PYRROLIDINE, BENZYL-SUBSTITUTED HETEROCYCLE CCR1 ANTAGONISTS FOR AUTOIMMUNE DISEASES & INFLAMMATION
  申请人：Paradkar Vidyadhar M.

  公开号：US20090093472A1

  公开（公告）日：2009-04-09

  Compounds of the formula are disclosed. The compounds are CCR1 antagonists which are useful for the treatment and prevention of inflammatory and autoimmune diseases. Other embodiments are also disclosed.

  公式为的化合物已被披露。这些化合物是CCR1拮抗剂，可用于治疗和预防炎症性和自身免疫性疾病。其他实施例也已披露。
• Enzyme-catalyzed enantiomeric resolution of N-Boc-proline as the key-step in an expeditious route towards RAMP
  作者：Masayuki Kurokawa、Takeyuki Shindo、Masumi Suzuki、Nobuyoshi Nakajima、Kohji Ishihara、Takeshi Sugai

  DOI：10.1016/s0957-4166(03)00210-6

  日期：2003.5

  For the preparation of both enantiomers of N-carbamoyl-2-methoxymethylpyrrolidine, the precursors of Enders’ chiral auxiliaries, SAMP and RAMP, enzyme-catalyzed kinetic resolution of racemic N-carbamoyl, N-Boc, N-Cbz proline esters and prolinols were examined. B. licheniformis protease (subtilisin) preferentially hydrolyzed the (R)-carbamoylproline ester with an enantiomeric ratio (E) of 10. To a hydrophobic

  对于两种对映体的制备Ñ -氨基甲酰基-2-甲氧基甲基，的恩德斯手性助剂，SAMP和RAMP的前体，酶催化的外消旋的动力学拆分Ñ -氨基甲酰基，Ñ -Boc，Ñ -Cbz脯氨酸酯和脯氨醇为检查。地衣芽孢杆菌蛋白酶（枯草杆菌蛋白酶）优先水解（R）-氨基甲酰基脯氨酸酯，对映体比率（E）为10。枯草杆菌蛋白酶对疏水性N -Cbz脯氨酸酯显示出较低的选择性（E = 2.8），相反，纯化的蛋白酶（同工酶A）对（S）-对映体（E= 13.6）。在实际意义上，南极衣原体脂肪酶B（Chirazyme L-2）可有效水解E> 100的N -Boc和N -Cbz衍生物。（R）-N-氨基甲酰基-2-甲氧基甲基吡咯烷酮的ee通过在N -Boc-脯氨醇阶段重结晶而提高到> 99.9％，该阶段衍生自（R）-N -Boc-脯氨酸甲酯（98.7 ％ee）通过外消旋底物的制备规模的酶催化拆分（49％收率）。
• <i>trans</i>-Hydrogenation: Application to a Concise and Scalable Synthesis of Brefeldin A
  作者：Michael Fuchs、Alois Fürstner

  DOI：10.1002/anie.201411618

  日期：2015.3.23

  The approach described herein is clearly more efficient; it hinges upon the first implementation of ruthenium‐catalyzed trans‐hydrogenation in natural products total synthesis. Because this unorthodox reaction is selective for the triple bond and does not touch the transannular alkene or the lactone site of the cycloalkyne, it outperforms the classical Birch‐type reduction that could not be applied at

  重要的生化探针分子布雷菲德菌素 A (brefeldin A) ( 1 ) 过去一直是一个鼓舞人心的目标，但根据记录，许多路线实际上都没有提供超过几毫克的产品。本文描述的方法显然更有效；它取决于钌催化的反式氢化在天然产物全合成中的首次实现。由于这种非正统反应对三键具有选择性，并且不接触跨环烯烃或环炔的内酯位点，因此它优于经典的 Birch 型还原反应，而经典的 Birch 型还原反应在如此晚的阶段无法应用。通往1 的其他关键步骤包括铁催化还原形成非末端炔烃、由大体积氨基醇介导的不对称丙炔酸酯羰基加成，以及由钼亚烷基催化的闭环炔烃复分解的大环化。
• PYRAZOLOQUINOLONES ARE POTENT PARP INHIBITORS
  申请人：PENNING D. THOMAS

  公开号：US20070249597A1

  公开（公告）日：2007-10-25

  Compounds of Formula (I) inhibit the PARP enzyme and are useful for treating a disease or a disorder associated with PARP. Also disclosed are pharmaceutical compositions comprising compounds of Formula (I), methods of treatment comprising compounds of Formula (I), and methods of inhibiting the PARP enzyme comprising compounds of Formula (I).

  化合物(I)的公式可以抑制PARP酶，并且可用于治疗与PARP相关的疾病或紊乱。此外，还披露了包含化合物(I)的药物组合物，包括化合物(I)的治疗方法，以及包括化合物(I)的抑制PARP酶的方法。