2,5-dioxopyrrolidin-1-yl 2-(tritylthio)acetate | 91425-31-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 2,5-dioxopyrrolidin-1-yl 2-(tritylthio)acetate
• 英文别名: 2,5-Pyrrolidinedione, 1-[[[(triphenylmethyl)thio]acetyl]oxy]-；(2,5-dioxopyrrolidin-1-yl) 2-tritylsulfanylacetate
• CAS: 91425-31-9
• 化学式: C₂₅H₂₁NO₄S
• 分子量: 431.512
• InChiKey: BNXCNXBRSGOGNL-UHFFFAOYSA-N

物化性质

• 沸点：
  550.8±52.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  89
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,5-dioxopyrrolidin-1-yl 2-(tritylthio)acetate 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 sodium hydroxide 、 乙腈 为溶剂， 反应 4.0h， 生成 N-[[(triphenylmethyl)thio]acetyl]-L-valylglycyl-L-glutamine
  参考文献：
  名称：

  SYNTHESIS BIODISTRIBUTION AND QSAR STUDIES OF FIVE Tc-99M LABELED NOVEL N3S PSEUDO-PEPTIDE COMPLEXES

  摘要：

  Five novel N3S pseudo-peptide chelators derived from mercaptoacetic acid have been synthesized and characterized based on the spectroscopic data. All the chelators were labeled with Technicium-99m to evaluate their biological activities. Investigations of their biodistribution in mice showed all five pseudo-peptide chelators (MGQ, MGGQ, MAGQ, MVGQ, MFGQ) are rapidly cleared from blood, mainly through renal clearance. Tc-99m-MGGQ and Tc-99m-MVGQ had high kidney uptake, quick blood clearance and high activity ratios of kidney to blood, thus showing potential application as renal imaging agents. Quantitative structure-activity relationship studies were performed. Linear regression analysis between the logarithm of renal uptake value (log%ID) and the parameters obtained from the ZINDO/1 method elicited several equations that possessed certain predictive qualities, and may play a direct part in drug design and synthesis.

  DOI：

  10.1007/s00044-004-0124-5
• 作为产物：
  描述：

  三苯基甲醇 在 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 13.0h， 生成 2,5-dioxopyrrolidin-1-yl 2-(tritylthio)acetate
  参考文献：
  名称：

  用于开发多环肽库的非经典二硫键导向基序的设计和核糖体整合

  摘要：

  天然存在的富含二硫键的肽 (DRP) 的工程设计受到二硫键配对困难的严重阻碍。利用折叠导向基序和非经典的含硫醇氨基酸的新 DRP 易于折叠，具有预期的二硫键连接性，代表了一类用于开发肽配体和治疗剂的新型支架。然而，支架的有限多样性，特别是难以被核糖体翻译的非经典氨基酸[例如青霉胺(Pen)]的使用极大地阻碍了这些DRP的进一步开发和应用。这里，我们设计并合成了非经典的二硫醇基序，它们带有类似于 Pen 硫醇的空间位阻硫醇基团，以指导肽折叠成特定的双环和三环结构。这些双硫醇基序可以通过与遗传密码重编程集成的市售 PURE 系统以核糖体方式掺入肽中，这首次实现了具有两个非规范和正交二硫键的双环肽的体外表达。我们进一步构建了一个由mRNA编码的双环肽库，并成功筛选出对蛋白质具有纳摩尔亲和力的新型双环肽配体。因此，本研究提供了一种新的、通用的和稳健的方法，用于发现具有非天然肽的新结构和功能的从头 DRP，

  DOI：

  10.1021/jacs.2c00216

文献信息

• 신규 mTOR 억제제 화합물 및 이의 용도
  申请人：Ewha University - Industry Collaboration Foundation 이화여자대학교 산학협력단(220040083301) BRN ▼110-82-10456

  公开号：KR20210023576A

  公开（公告）日：2021-03-04

  본 발명의 신규 mTOR 억제제 화합물은 뼈에 대하여 선택적으로 약물 전달이 가능하며 뼈에서 오랜 기간 서서히 방출될 수 있도록, 골 지향성 리간드를 mTOR 억제 뼈 질환 치료제에 연결한 표적지향성 화합물에 관한 것이다.

  这项新型 mTOR 抑制剂化合物能够选择性地在骨骼中进行药物传递，并且能够在骨骼中缓慢释放长时间，这是关于将骨向性配体连接到 mTOR 抑制剂骨疾病治疗剂的靶向化合物的。
• Synthesis, high-field NMR, X-ray structure, and conformational analysis of a 10-membered diamide disulfide ring
  作者：Rabindranath B. Maharajh、James P. Snyder、James F. Britten、Russell A. Bell

  DOI：10.1139/v97-018

  日期：1997.2.1

  N,N′-[Dimethyl-(2,2′-dithiobisacetyl)]ethylenediamine (1) has been synthesized in 30% overall yield from N,N′-dimethylethylenediamine and thioacetic acid by an improved procedure involving simultaneous deprotection and oxidative cyclization with iodine. This cyclic diamide disulfide exists in solution as a mixture of two Z,Z and one Z,E disulfide, and amide ring conformers and has been characterized by nuclear Overhauser effect (NOE), ¹H–¹H, ¹H–¹³C shift-correlated 2D-NMR and molecular modelling studies. Among the Z,Z ring conformers Z,Z₁ and Z,Z₂, the former predominates and interconverts with the latter isomer by rotation about the S—S bond with an activation energy of 14.5 ± 1.3 kcal/mol. Coalescence of N-CH₃ signals occurred at ca. 127 °C (500 MHz), which corresponded to an approximate barrier to amide rotation of 19.3 kcal/mol. Aromatic solvent-induced shifts in C₆D₆ corroborated molecular mechanics and NOE predictions of amide stereochemistry. The structure of the Z,E stereoisomer of 1 has been determined by single-crystal X-ray diffraction at 296 K. A large geminal N-CH₂ inequivalence (>2 ppm in CDCl₃) was observed for the Z,Z conformers. Proton chemical shifts have been calculated for the conformers of 1 and related molecular fragments with DFT/GIAO theory. Absolute chemical shifts are modelled within 0.2 ppm of experiment. The unusual nonequivalence of geminal N-CH₂ and S-CH₂ protons can be understood as a combination of shielding mechanisms derived from short N-methyl contacts, amide group orientation, and sulfur lone-pair disposition. An implication of these results is the possibility of using α-CH (and eventually α-CH) shifts to probe the local conformational space in cyclic peptides and other conformationally constrained rings. Keywords: amide/disulfide rotamers, conformational analysis, density functional theory, DFT/GIAO NMR shift calculations, methylene nonequivalence, molecular modelling.

  N,N′-[二甲基-(2,2′-二硫代乙酰)]乙二胺（1）已经通过一种改进的程序从N,N′-二甲基乙二胺和硫乙酸合成，总产率为30％。该程序涉及使用碘同时去保护和氧化环化。这种环状二酰胺二硫化物在溶液中存在为两种Z,Z和一种Z,E二硫化物的混合物，以及酰胺环构象，并通过核Overhauser效应（NOE）、1H-1H、1H-13C移位相关的二维NMR和分子建模研究进行了表征。在Z,Z环构象Z,Z1和Z,Z2中，前者占主导地位，并通过绕S-S键的旋转以14.5 ± 1.3 kcal/mol的活化能与后者异构体相互转化。N-CH3信号在约127°C（500MHz）处共聚，对应于约19.3 kcal/mol的酰胺旋转的近似能垒。芳香溶剂诱导的C6D6中的移位证实了酰胺立体化学的分子力学和NOE预测。通过单晶X射线衍射在296K下确定了1的Z,E立体异构体的结构。对于Z,Z构象观察到了大的geminal N-CH2不对称性（在CDCl3中大于2 ppm）。使用DFT/GIAO理论计算了1和相关分子片段的构象体的质子化学位移。绝对化学位移在实验中模拟了0.2 ppm。geminal N-CH2和S-CH2质子的不寻常不对称性可以理解为来自短N-甲基接触、酰胺基取向和硫孤对位置的屏蔽机制的组合。这些结果的一个含义是可以利用α-CH（最终是α-CH）位移来探测环肽和其他构象受限环中的局部构象空间。关键词：酰胺/二硫化物转构体、构象分析、密度泛函理论、DFT/GIAO NMR位移计算、亚甲基不对称性、分子建模。
• The synthesis and high-resolution NMR spectroscopy of ethyl <i>N</i>-(2-triphenylmethylthio)ethanoyl-<i>O</i>-{4′-[4″-(1″-bis(2″′-chloroethyl)amino)phenyl]butanoyl}-<scp>L</scp>-seryl-<i>S</i>-benzyl-<scp>L</scp>-cysteine: a chelate–chlorambucil complex for use as a ligand for ^99mTc radio-imaging
  作者：Russell A. Bell、Donald W. Hughes、Colin J.L. Lock、John F. Valliant

  DOI：10.1139/v96-167

  日期：1996.8.1

  A potential agent for the imaging of tumours has been synthesized from the antineoplastic agent chlorambucil. Standard peptide coupling techniques were used to synthesize a tripeptide covalently coupled to chlorambucil in 10 steps. The final product was characterized by high-resolution NMR spectroscopy. Key words: ethyl N-triphenylmethylthioethanoyl-O-4′-[4″-(1"-bis(2″′-chloroethyl)amino)phenyl]butanoyl}-L-seryl-S-benzyl-L-cysteine, NMR spectroscopy, synthesis, radio-imaging agent.

  一种用于肿瘤成像的潜在试剂已经从抗肿瘤药物氯氨丁胺合成。标准的肽偶联技术被用于在10个步骤中合成与氯氨丁胺共价结合的三肽。最终产物通过高分辨率核磁共振波谱进行表征。关键词：乙基N-三苯基甲硫基乙酰-O-4′-[4″-(1"-双(2″′-氯乙基)氨基)苯基]丁酰}-L-丝氨酰-S-苄基-L-半胱氨酸，核磁共振波谱，合成，放射成像试剂。
• Design and synthesis of a novel family of semi-rigid ligands: versatile compounds for the preparation of 99mTc radiopharmaceuticals
  作者：Julien Le Gal、Laure Latapie、Marie Gressier、Yvon Coulais、Mich�le Dartiguenave、Eric Benoist

  DOI：10.1039/b313996d

  日期：——

  Synthetic pathways to a range of novel semi-rigid tetradentate ligands, with sulfur, amido or amino donor groups, designed to coordinate technetium 99m have been developed. The technetium-99m complexes have been prepared and their stabilities in serum and by metathesis reaction via cysteine exchange reactions were compared. HPLC comparison of two (99m)Tc-complexes and their rhenium analogues led to

  已开发出设计用于协调99 99m的一系列新型半刚性四齿配体（具有硫，酰胺基或氨基供体基团）的合成途径。制备了-99m配合物，并比较了它们在血清中的稳定性以及通过半胱氨酸交换反应进行的复分解反应的稳定性。两种（99m）Tc配合物及其their类似物的HPLC比较导致我们放射性配合物性质的第一个证明。
• A practical approach to the synthesis of hairpin polyamide–peptide conjugates through the use of a safety-catch linker
  作者：Daniela Fattori、Olaf Kinzel、Paolo Ingallinella、Elisabetta Bianchi、Antonello Pessi

  DOI：10.1016/s0960-894x(02)00122-1

  日期：2002.4

  sequence selective DNA binders. The use of a safety-catch linker for the solid phase synthesis of hairpin polyamides allows for easy preparation of derivatives ready for chemoselective ligation with unprotected peptides. Examples of ligations reported include thioether bond formation and thioester-mediated amide bond formation ('Native Chemical Ligation').

  发夹聚酰胺是高亲和力的，序列选择性的DNA结合剂。使用安全捕获接头用于发夹聚酰胺的固相合成可轻松制备易于与未保护的肽进行化学选择性连接的衍生物。报道的连接的例子包括硫醚键形成和硫酯介导的酰胺键形成（“天然化学连接”）。