N-(苯基甲氧基羰基)-L-异亮氨酸 2,5-二氧代-1-吡咯烷基酯 | 3391-99-9

• 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: N-(苯基甲氧基羰基)-L-异亮氨酸 2,5-二氧代-1-吡咯烷基酯
• 中文别名: Z-L-异亮氨酸羟基琥珀酰亚胺酯；N-(苯基甲氧基羰基)-L-异亮氨酸2,5-二氧代-1-吡咯烷基酯；N-CBZ-L-异亮氨酸N-羟基琥珀酰亚胺酯
• 英文名称: N-Z-L-isoleucine N-hydroxysuccinimide ester
• 英文别名: Z-Ile-OSu；(2,5-dioxopyrrolidin-1-yl) (2S,3S)-3-methyl-2-(phenylmethoxycarbonylamino)pentanoate
• CAS: 3391-99-9
• 化学式: C₁₈H₂₂N₂O₆
• 分子量: 362.382
• InChiKey: XQPVVBMUTQVELT-LRDDRELGSA-N

物化性质

• 熔点：
  111-112 °C
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• WGK Germany：
  3
• 储存条件：
  2-8℃，惰性气体

反应信息

• 作为反应物：
  描述：

  N-(苯基甲氧基羰基)-L-异亮氨酸 2,5-二氧代-1-吡咯烷基酯 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 28.0h， 生成 Cbz-Ile-Ala(SO2Bn)-OSu
  参考文献：
  名称：

  Optimization of Subsite Binding to the β5 Subunit of the Human 20S Proteasome Using Vinyl Sulfones and 2-Keto-1,3,4-oxadiazoles:  Syntheses and Cellular Properties of Potent, Selective Proteasome Inhibitors

  摘要：

  Beginning with the peptide sequence Cbz-Ile-Glu(OtBu)-Ala-Leu found in PSI (3), a series of vinyl sulfones (VS) were synthesized for evaluation as inhibitors of the chymotrypsin-like activity of the 20S proteasome. Variations at the key P3 position confirmed the importance of a long side chain capped with a hydrophobic group for optimal potency, consistent with a model of binding to the S3 subsite. The tert-butyl glutamic ester initially used at P3 gave plasma unstable, insoluble compounds and was replaced with the better isostere, N-beta-neopentyl asparagine. The inhibitors were shortened by replacing the N-terminal Cbz-isoleucine with a p-tosyl group without loss of potency. Small L-amino acids were used at P2, where D-substitution was not tolerated. The resulting optimized P4-P3-P2 sequence was grafted onto a novel proteasome inhibitor warhead, 2-keto-1,3,4-oxadiazoles (KOD), to produce reversible, subnanomolar proteasome inhibitors that were 1000-fold selective versus cathepsin B (CatB), cathepsin S (CatS), and trypsin-like as well as PGPH-like proteasome activity. A number of compounds in both the VS and the KOD series exhibited growth inhibitory effects against the human prostate cancer cell line PC3 at submicromolar concentrations.

  DOI：

  10.1021/jm058289o
• 作为产物：
  描述：

  N-苄氧羰基-L-异亮氨酸 在 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 N-(苯基甲氧基羰基)-L-异亮氨酸 2,5-二氧代-1-吡咯烷基酯
  参考文献：
  名称：

  氨基酸型低分子量三（双酰胺基）有机胶凝剂†

  摘要：

  设计，合成了两种新型的基于氨基酸的低分子有机胶凝剂，并研究了它们胶凝各种有机溶剂的能力。发现胶凝剂分子通过N–H⋯O氢键聚集形成缠绕的3D网络，该网络固定了大量有机溶剂。在凝胶研究中使用的不同有机溶剂中均三甲苯被发现是最好的溶剂。用FESEM和光学显微照片研究了有机凝胶的微观结构。使用与温度相关的1 H NMR研究了氢键在胶凝剂分子聚集中的参与。发现获得的有机凝胶表现出显着的机械强度。

  DOI：

  10.1039/c0sm01293a

文献信息

• An Efficient Procedure for the Preparation of Carboxamides and Peptides using<i>in situ</i>Generated<i>N</i>-Succinimidyl Active Esters
  作者：Ki-Jong Han、Misoo Kim

  DOI：10.1080/00304948.2014.922380

  日期：2014.7.4

  last two decades.8–15 Previously, we reported the synthesis of N-hydroxysuccinimide esters of carboxylic acids using triphosgene.16 In continuation of our work to develop new methods using triphosgene as an acid activator,17,18 we report herein an efficient one-pot procedure for the synthesis of carboxamides and peptides using N-succinimidyl active esters generated in situ directly from the reaction of

  羧酰胺部分是生物活性化合物（如肽）中最重要的官能团之一。1,2 大多数羧酰胺和肽的制备方法都基于活化的羧酸与胺的反应。3,4 N-琥珀酰亚胺活性酯是肽合成中有价值的中间体，因为它们与多种胺反应可产生相应的酰胺。 5-7 三光气以白色固体形式在市场上出售，其效用在过去二十年中得到了广泛研究。 8 –15 之前，我们报道了使用三光气合成 N-羟基琥珀酰亚胺羧酸酯。 16 在继续我们开发使用三光气作为酸活化剂的新方法的工作中，17，在图 18 中，我们报告了一种使用 N-琥珀酰亚胺活性酯合成羧酰胺和肽的有效一锅法，该酯直接由羧酸与 N-羟基琥珀酰亚胺 (NHS) 在三光气存在下的反应原位生成（方案 1）。 8
• Mechanistic implications of the enantioselective addition of alkylzinc reagents to aldehydes catalyzed by nickel complexes with α-amino amide ligands
  作者：Jorge Escorihuela、M. Isabel Burguete、Gregori Ujaque、Agustí Lledós、Santiago V. Luis

  DOI：10.1039/c6ob01878e

  日期：——

  The enantioselective alkylation of aldehydes catalysed by nickel(II)-complexes derived from α-amino amides was studied by means of density functional theory (DFT) and ONIOM (B3LYP:UFF) calculations. A mechanism was proposed in order to investigate the origin of enantioselectivity. The chirality-determining step for the alkylation was the formation of the intermediate complexes with the involvement

  通过密度泛函理论（DFT）和ONIOM（B3LYP：UFF）计算研究了由α-氨基酰胺衍生的镍（II）配合物催化的醛的对映选择性烷基化。为了研究对映选择性的起源，提出了一种机制。烷基化的手性确定步骤是中间体配合物的形成，其中涉及5/4 / 4-稠合的三环过渡态。理论上预测的主要产物为（S）-构型，与实验观察结果非常吻合。检查了反应范围，观察到对映选择性添加Et 2 Zn和Me 2的高产率和对映选择性锌为芳香族和脂肪族醛。
• 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。
• Angiotensin-converting enzyme inhibitors: Synthesis and structure-activity relationships of potent N-benzyloxycarbonyl tripeptide inhibitors.
  作者：Tadahiro SAWAYAMA、Masatoshi TSUKAMOTO、Takashi SASAGAWA、Kazuya NISHIMURA、Ryuichi YAMAMOTO、Takashi DEGUCHI、Kunihiko TAKEYAMA、Kanoo HOSOKI

  DOI：10.1248/cpb.37.2417

  日期：——

  (Z) tripeptide inhibitors of angiotensin-converting enzyme (ACE) was synthesized. The effect of varying the antepenultimate amino acid residue in this series on the biological activity was studied. Introduction of Lys and Orn residues at the P1 position provided the most potent inhibitors, 25a and 25b (IC50: 3.5 and 4.9 x 10(-9) M, respectively), which exhibited an oral antihypertensive activity. This

  合成了一系列新的含γ-D-Glu的血管紧张素转化酶（ACE）的N-苄氧基羰基（Z）三肽抑制剂。研究了改变该系列中前倒数第二个氨基酸残基对生物活性的影响。在P1位置引入Lys和Orn残基可提供最有效的抑制剂25a和25b（IC50：分别为3.5和4.9 x 10（-9）M），具有口服降压活性。该结果表明，在该系列中，P1位的碱性氨基酸残基在与ACE的S1亚位点的结合中起重要作用。评价了所选化合物的口服降压活性。
• Structural insight into the aggregation of <scp>l</scp>-prolyl dipeptides and its effect on organocatalytic performance
  作者：Cristina Berdugo、Beatriu Escuder、Juan F. Miravet

  DOI：10.1039/c4ob02003k

  日期：——

  NMR and organocatalytic studies of four dipeptides derived from l-proline are described.

  NMR和有机催化研究了从L-脯氨酸衍生的四个二肽。