O-mesyl-N-trityl-D-serine methyl ester | 116457-92-2

• 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: O-mesyl-N-trityl-D-serine methyl ester
• 英文别名: O-(Methylsulfonyl)-N-(triphenylmethyl)-D-serine methyl ester；methyl (2R)-3-methylsulfonyloxy-2-(tritylamino)propanoate
• CAS: 116457-92-2
• 化学式: C₂₄H₂₅NO₅S
• 分子量: 439.532
• InChiKey: ULZIFBTVXNOMFL-JOCHJYFZSA-N

物化性质

• 沸点：
  606.4±55.0 °C(Predicted)
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.09
• 重原子数：
  31.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  81.7
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  O-mesyl-N-trityl-D-serine methyl ester 在 lithium aluminium tetrahydride 、 sodium methylate 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 64.0h， 生成 [3-hexadecylsulfanyl-2-(tritylamino)propyl] 2-(trimethylazaniumyl)ethyl phosphate
  参考文献：
  名称：

  A new approach to the synthesis of thioether phospholipids. Preparation of 1-thiohexadecyl-2-N-acylaminodeoxyglycerophosphocholines

  摘要：

  DOI：

  10.1016/0040-4039(88)80008-x
• 作为产物：
  描述：

  三苯基氯甲烷 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 O-mesyl-N-trityl-D-serine methyl ester
  参考文献：
  名称：

  一种LZC696中间体及其合成方法

  摘要：

  本发明公开了一种化合物，所述化合物为(R)‑叔丁基(1‑((1,1’联苯)‑4‑基)3‑((叔丁基二甲基硅基)氧)丙烷‑2‑基)氨基甲酸酯，其结构式如式A所示：A。采用这种化合物合成LZC696中间体，整个工艺过程没有昂贵的试剂和原料，无对氧气敏感反应，纯化程序简单，只需要在化合物3和最终产品重结晶纯化就可以达到商业化使用纯度。本发明合成工艺成本低，简单环保，适合工业化放量生产。

  公开号：

  CN105237560B

文献信息

• Proteomic searches comparing two (R)-lacosamide affinity baits: An electrophilic arylisothiocyanate and a photoactivated arylazide group
  作者：Ki Duk Park、James P. Stables、Rihe Liu、Harold Kohn

  DOI：10.1039/c000987c

  日期：——

  We have advanced a novel strategy to search for lacosamide ((R)-1) targets in the brain proteome where protein binding is expected to be modest. Our approach used lacosamide agents containing “affinity bait” (AB) and “chemical reporter” (CR) units. The affinity bait moiety is designed to irreversibly react with the target, and the CR group permits protein detection and capture. In this study, we report the preparation and evaluation of (R)-N-(4-azido)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-3) and show that this compound exhibits potent anticonvulsant activities in the MES seizure model in rodents. We compared the utility of (R)-3 with its isostere, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-2), in proteomic studies designed to identify potential (R)-1 targets. We showed that despite the two-fold improved anticonvulsant activity of (R)-3 compared with (R)-2, (R)-2 was superior in revealing potential binding targets in the mouse brain soluble proteome. The difference in these agents’ utility has been attributed to the reactivity of the affinity baits (i.e., (R)-2: aryl isothiocyanate moiety; (R)-3: photoactivated aryl azide intermediates) in the irreversible protein modification step, and we conclude that this factor is a critical determinant of successful target detection where ligand (drug) binding is modest. The utility of (R)-2 and (R)-3 in in situ proteome studies is explored.

  我们提出了一种新颖的策略，在蛋白质结合度较低的大脑蛋白质组中寻找拉科酰胺（(R)-1）靶标。我们的方法使用了含有 "亲和诱饵"（AB）和 "化学报告"（CR）单元的拉科酰胺制剂。亲和诱饵分子被设计成与靶标发生不可逆反应，而 CR 基团则允许蛋白质检测和捕获。在这项研究中，我们报告了 (R)-N-(4-azido)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide （(R)-3）的制备和评估，结果表明这种化合物在啮齿动物的 MES 癫痫模型中表现出强效抗惊厥活性。我们比较了(R)-3 和它的同系物(R)-N-(4-异硫氰基)苄基 2-乙酰氨基-3-(丙-2-炔氧基)丙酰胺（(R)-2）在蛋白质组学研究中的作用，这些研究旨在确定潜在的(R)-1 靶点。我们发现，尽管(R)-3 的抗惊厥活性比(R)-2 提高了两倍，但(R)-2 在揭示小鼠大脑可溶性蛋白质组中的潜在结合靶点方面更胜一筹。这些药剂的效用差异归因于亲和饵料（即 (R)-2：芳基异硫氰酸酯分子；(R)-3：光活化芳基叠氮中间体）在不可逆蛋白质修饰步骤中的反应性。我们探讨了 (R)-2 和 (R)-3 在原位蛋白质组研究中的用途。
• Lacosamide Isothiocyanate-Based Agents: Novel Agents To Target and Identify Lacosamide Receptors
  作者：Ki Duk Park、Pierre Morieux、Christophe Salomé、Steven W. Cotten、Onrapak Reamtong、Claire Eyers、Simon J. Gaskell、James P. Stables、Rihe Liu、Harold Kohn

  DOI：10.1021/jm9012054

  日期：2009.11.12

  (R)-Lacosamide ((R)-2, (R)-N-benzyl 2-acetamido-3-methoxypropionamide) has recently gained regulatory approval for the treatment of partial-onset seizures in adults. Whole animal pharmacological studies have documented that (R)-2 function is unique: A robust strategy is advanced for the discovery of interacting proteins associated with function and toxicity of (R)-2 through the use of (R)-2 analogues, 3, which contain "affinity bait (AB)" and "chemical reporter (CR)" functional groups. In 3, covalent modification of the interacting proteins proceeds at the AB moiety, and detection or isolation of the selectively captured protein occurs through the bioorthogonal CR group upon reaction with all appropriate probe. We report the synthesis, pharmacological evaluation, and interrogation of the mouse soluble brain proteome using 3 where the AB group is an isothiocyanate moiety. One compound, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-9), exhibited excellent Seizure protection in mice, and like (R)-2, anticonvulsant activity principally resided in the (R)-stereoisomer. Several proteins were preferentially labeled by (R)-9 compared with (S)-9, including collapsin response mediator protein 2.
• [EN] NOVEL N-BENZYLAMIDE SUBSTITUTED DERIVATIVES OF 2-(ACYLAMIDO)ACETIC ACID AND 2-(ACYLAMIDO)PROPIONIC ACIDS: POTENT NEUROLOGICAL AGENTS<br/>[FR] NOUVEAUX DÉRIVÉS SUBSTITUÉS PAR N-BENZYLAMIDE D'ACIDE 2-(ACYLAMIDO)ACÉTIQUES ET ACIDES 2-(ACYLAMIDO)PROPIONIQUES : AGENTS NEUROLOGIQUES PUISSANTS
  申请人：UNIV NORTH CAROLINA

  公开号：WO2009145816A3

  公开（公告）日：2010-02-25
• Kato, Shiro; Harada, Hiroshi; Morie, Toshiya, Journal of the Chemical Society. Perkin transactions I, 1997, # 21, p. 3219 - 3225
  作者：Kato, Shiro、Harada, Hiroshi、Morie, Toshiya

  DOI：——

  日期：——
• Studies on the synthesis of orthogonally protected azalanthionines, and of routes towards β-methyl azalanthionines, by ring opening of N-activated aziridine-2-carboxylates
  作者：Keith O'Brien、Keith ó Proinsias、Fintan Kelleher

  DOI：10.1016/j.tet.2014.06.011

  日期：2014.8

  Orthogonally protected azalanthionines were successfully synthesised by the ring-opening of N-activated aziridine-2-carboxylates with protected diaminopropanoic acids (DAPs). The required DAPs were also prepared by ring-opening of N-activated aziridine-2-carboxylates with para-methoxybenzylamine, but it was found that the choice of aziridine protecting groups dictated both the success of the reaction as well as the regioselectivity of the isolated products. Attempts to extend the methodology to the preparation of the more sterically demanding beta-methyl azalanthionines have, so far, been unsuccessful. (C) 2014 Elsevier Ltd. All rights reserved.