benzyl (S)-(1-hydroxy-3-(1H-indol-3-yl)propan-2-yl)carbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl (S)-(1-hydroxy-3-(1H-indol-3-yl)propan-2-yl)carbamate
• 英文别名: N-benzyloxycarbonyl-(L)-tryptophanol；benzyl N-[(2S)-1-hydroxy-3-(1H-indol-3-yl)propan-2-yl]carbamate
• 化学式: C₁₉H₂₀N₂O₃
• 分子量: 324.379
• InChiKey: LUYGYUGZSGMKOX-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  74.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl (S)-(1-hydroxy-3-(1H-indol-3-yl)propan-2-yl)carbamate 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 L-色氨醇
  参考文献：
  名称：

  Synthesis of Peptide Aldehyde Derivatives as Selective Inhibitors of Human Cathepsin L and Their Inhibitory Effect on Bone Resorption

  摘要：

  Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 Of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.

  DOI：

  10.1021/jm9803065
• 作为产物：
  描述：

  (S)-N-benzyloxycarbonyl-L-tryptophan methyl ester 在 锂硼氢 作用下， 以 四氢呋喃 为溶剂， 生成 benzyl (S)-(1-hydroxy-3-(1H-indol-3-yl)propan-2-yl)carbamate
  参考文献：
  名称：

  （-）-吲哚内酰胺-V的区域和立体控制的全合成

  摘要：

  由L-色氨酸甲酯以10个步骤制备（-）-吲哚内酰胺-V（IL-V）（1），总产率为17.1％。关键步骤包括酰基环中间体（4）的区域特异的thallation ，然后叠氮化物置换和还原以引入13-氨基。通过衍生自D-缬氨酸的手性膨胀剂（10）的S N 2置换来实现对C-11立体中心的控制。al介导的二肽的封闭（17）没有提供替代途径通往IL-V。

  DOI：

  10.1016/s0040-4020(01)87853-4

文献信息

• Enantioselective Friedel–Crafts reactions between phenols and N-tosylaldimines catalyzed by a leucine-derived bifunctional catalyst
  作者：Guo-Xing Li、Jin Qu

  DOI：10.1039/c2cc31735d

  日期：——

  Enantioselective Friedel–Crafts reactions between phenols and N-tosylaldimines were developed using a bifunctional catalyst readily prepared from L-leucine. The chiral benzylic amine products were obtained in high yields (up to 96% yield) and good to high enantiomeric excesses (up to 95% ee).

  利用L-亮氨酸作为原料制备的二功能催化剂，开发了苯酚与N-对甲苯磺酰亚胺之间的对映选择性Friedel-Crafts反应。获得了高产率（最高达96%）和良好至高对映体过量（最高达95% ee）的手性苄胺产物。
• Synthesis of a .BETA.-Tetrapeptide Analog as a Mother Compound for the Development of Matrix Metalloproteinase-2-Imaging Agents
  作者：Takahiro Mukai、Noriko Suganuma、Kenta Soejima、Junichi Sasaki、Fumihiko Yamamoto、Minoru Maeda

  DOI：10.1248/cpb.56.260

  日期：——

  Matrix metalloproteinase-2 (MMP-2) is an attractive target for the diagnosis of cancer and atherosclerosis in nuclear imaging. A cyclic decapeptide, cCTTHWGFTLC (cCTT), has been used as the mother compound for the development of MMP-2-imaging agents with high potency and selectivity. Most of radiolabeled derivatives of cCTT currently developed for in vivo studies of MMP-2, however, suffer from low accumulation in the target tissues, such as tumors. For enhanced in vivo stability and tissue penetration, we designed a linear β-tetrapeptide analog, H-β3-Phe-β-Ala-β3-Trp-β3-His-OH (1), to mimic cCTT. The component β-amino acids were prepared by reduction of N-protected α-amino acid methyl esters to the alcohols, followed by conversion into the cyanides, and subsequent hydrolysis. Compound 1 was obtained from these β-amino acids by the conventional solution method. In MMP-2 inhibition assay, compound 1 displayed desirably significant inhibition, which was comparable to cCTT. These findings suggest that compound 1 may serve as a mother compound in the design and development of in vivo MMP-2-imaging agents.

  基质金属蛋白酶-2(MMP-2)是核成像中诊断癌症和动脉粥样硬化的理想靶点。环状十肽cCTTHWGFTLC(cCTT)已被用作开发高效能和选择性的MMP-2成像剂的母体化合物。然而，目前开发的大多数cCTT放射性标记衍生物在体内研究MMP-2时，在目标组织如肿瘤中的积累较低。为了提高体内稳定性和组织穿透性，我们设计了一种线性β-四肽类似物H-β3-Phe-β-Ala-β3-Trp-β3-His-OH(1)，以模拟cCTT。这些β-氨基酸成分是通过将N-保护的α-氨基酸甲酯还原为醇，然后转化为氰化物，最后进行水解得到的。化合物1是通过传统的溶液方法从这些β-氨基酸制备的。在MMP-2抑制测定中，化合物1显示出显著的抑制效果，与cCTT相当。这些发现表明，化合物1可能在设计和发展体内MMP-2成像剂中作为母体化合物。
• Synthesis of Aminomethylene-<i>gem</i>-bisphosphonates Containing an Aziridine Motif: Studies of the Reaction Scope and Insight into the Mechanism
  作者：Thomas Cheviet、Suzanne Peyrottes

  DOI：10.1021/acs.joc.0c02434

  日期：2021.2.19

  Study of the reaction’s scope and additional experiments indicates that the transformation proceeds via a new mechanism involving the chelation of lithium ion. This last step is crucial for the reaction to occur and disfavors the aziridine ring-opening. A phosphonate–phosphate rearrangement from a α-hydroxybisphosphonate aziridine intermediate is also proposed for the first time. This reaction provides

  获得了广泛的N-氨基甲酰基氮丙啶，然后用二乙基膦酸根阴离子处理，得到α-亚甲基-宝石-双膦酸酯氮丙啶。对反应范围和其他实验的研究表明，转化是通过涉及锂离子螯合的新机理进行的。这最后一步对于反应的发生至关重要，不利于氮丙啶开环。还首次提出了由α-羟基双膦酸酯氮丙啶中间体进行的膦酸酯-磷酸重排。该反应提供了用于合成高度官能化的膦酰化氮丙啶基序的简单方便的方法。
• [EN] ESTROGEN RECEPTOR MODULATORS<br/>[FR] MODULATEURS DU RÉCEPTEUR DES ŒSTROGÈNES
  申请人：KALYRA PHARMACEUTICALS INC

  公开号：WO2017172957A1

  公开（公告）日：2017-10-05

  Compounds of Formula (I) are estrogen receptor alpha modulators, where the variables in Formula (I) are described in the disclosure. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions that are estrogen receptor alpha dependent and/or estrogen receptor alpha mediated, including conditions characterized by excessive cellular proliferation, such as breast cancer.

  化合物的化学式（I）是雌激素受体α调节剂，其中化学式（I）中的变量在披露中有描述。这些化合物以及其药学上可接受的盐和组合物对于治疗依赖雌激素受体α和/或由雌激素受体α介导的疾病或症状是有用的，包括由细胞过度增殖所特征化的疾病，如乳腺癌。
• Efficient Access to Enantiopure γ⁴-Amino Acids with Proteinogenic Side-Chains and Structural Investigation of γ⁴-Asn and γ⁴-Ser in Hybrid Peptide Helices
  作者：Sandip V. Jadhav、Rajkumar Misra、Sumeet K. Singh、Hosahudya N. Gopi

  DOI：10.1002/chem.201302732

  日期：2013.11.25

  to fold into ordered helical structures. As amino acid side‐chain functional groups play a crucial role in the biological context, the objective of this study was to investigate efficient synthesis of γ4‐residues with functional proteinogenic side‐chains and their structural analysis in hybrid‐peptide sequences. Here, the efficient and enantiopure synthesis of various N‐ and C‐terminal free‐γ4‐residues

  由α-和β-氨基酸组成的杂合肽最近已成为一类新型的肽折叠剂。相比较而言，γ的组成γ-和混合γ-肽4 -氨基酸比其β-对应物少的研究。然而，最近的研究表明，γ 4 -氨基酸有较高的倾向折叠成有序的螺旋结构。作为氨基酸侧链的官能团起到生物上下文中的关键作用，本研究的目的是调查γ的有效合成4 -残基与官能蛋白原侧链和在混合的肽序列的结构分析。在这里，各种N-末端和C-末端游离-γ的有效和对映体纯合成4-残基，从苄基酯（COOBzl）起始Ñ -Cbz保护的（ë）- α，报道β不饱和γ氨基通过在单锅催化氢化多个氢解和双键还原酸。8未受保护的γ的结晶构象，4 -氨基酸（γ 4 -Val，γ 4 -Leu，γ 4 -Ile，γ 4 -Thr（O吨丁基），γ 4 -Tyr，γ 4 -Asp（O吨卜），γ 4 -Glu（O吨丁基），和γ-AIB）显示，这些氨基酸通过一个螺旋利于笨拙沿着中心Ç构象γ  Ç β键。来研究γ行为4