N,N,O-trimethylserine

• 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
• 英文名称: N,N,O-trimethylserine
• 英文别名: 2-(Dimethylamino)-3-methoxypropanoic acid
• 化学式: C₆H₁₃NO₃
• 分子量: 147.174
• InChiKey: NLPSBXAUFDUXAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N,O-trimethylserine 在 盐酸 、 氟化氢吡啶 作用下， 生成 2-Dimethylamino-3-methoxy-propionic acid (3E,5E,15E,21E)-(8R,9S,10R,11R,14S,18R,20R,24S)-24-((1S,2S,3S)-2,4-dihydroxy-1,3-dimethyl-butyl)-10-hydroxy-14,20-dimethoxy-9,11,18-trimethyl-2-oxo-oxacyclotetracosa-3,5,15,21-tetraen-8-yl ester
  参考文献：
  名称：

  Cytotoxicity and actin depolymerizing activity of aplyronine A, a potent antitumor macrolide of marine origin, and the natural and artificial analogs

  摘要：

  The artificial analogs of aplyronine A (1), a potent cytotoxic and antitumor macrolide, were synthesized and the structure-activity (cytotoxicity and actin depolymerizing activity) studies were performed; the side chain portion in 1 was found to play a key role in both biological activities. (C) 1997, Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(96)00620-8

文献信息

• Toward aplyronine payloads for antibody–drug conjugates: total synthesis of aplyronines A and D
  作者：Nika Anžiček、Simon Williams、Michael P. Housden、Ian Paterson

  DOI：10.1039/c7ob03204h

  日期：——

  potent congener aplyronine D together with a highly stereocontrolled synthesis of aplyronine A. To facilitate step economy, an adventurous site-selective esterification of the C7 hydroxyl group was performed to install the N,N,O-trimethylserine pharmacophore to directly afford aplyronines A and D. Toward the assembly of ADCs incorporating an aplyronine warhead, the C29-ester derivative 4 featuring an

  芹菜碱是一类抗有丝分裂的海洋大环内酯类，可通过双重靶向肌动蛋白和微管蛋白来破坏细胞骨架动力学。鉴于其皮摩尔的细胞毒性特征和空前的作用方式，其作为开发下一代用于癌症化学疗法的抗体-药物偶联物（ADC）的新型有效负载，是绝佳的候选者。通过改进大内酯核5的第二代合成，我们已经实现了最有效的同类素aplyronine D的首次全合成以及对aplyronine A的高度立体控制的合成。进行C7羟基安装N，N，O-trimethylserine药效团直接提供aplyronines A和D。在组装带有aplyronine战斗部的ADC的过程中，还通过适应这种灵活的末端操作制备了C29-酯衍生物4，其特征是Fmoc-氨基取代的连接子附着在肌动蛋白结合的尾巴区域上。
• Development of a novel inducer of protein–protein interactions based on aplyronine A
  作者：Takayuki Ohyoshi、Atsuhiro Takano、Mayu Namiki、Tomotaka Ogura、Yuto Miyazaki、Yuta Ebihara、Koichi Takeno、Ichiro Hayakawa、Hideo Kigoshi

  DOI：10.1039/c8cc04613a

  日期：——

  An aplyronine A–swinholide A hybrid, consisting of the macrolactone part of aplyronine A and the side chain part of swinholide A, was designed, synthesized, and evaluated for biological activities.

  一个由aplyronine A的大环内酯部分和swinholide A的侧链部分组成的混合物被设计、合成并用于生物活性评估。
• Second-generation total synthesis of aplyronine A featuring Ni/Cr-mediated coupling reactions
  作者：Ichiro Hayakawa、Keita Saito、Sachiko Matsumoto、Shinichi Kobayashi、Ayaka Taniguchi、Kenichi Kobayashi、Yusuke Fujii、Takahiro Kaneko、Hideo Kigoshi

  DOI：10.1039/c6ob02241c

  日期：——

  Second-generation total synthesis of aplyronine A, a potent antitumor marine macrolide, was achieved using Ni/Cr-mediated coupling reactions as key steps. The overall yield of the second-generation synthetic pathway of aplyronine A was 1.4%, obtained in 38 steps based on the longest linear sequence. Compared to our first-generation synthetic pathway of aplyronine A, the second-generation synthesis greatly improved

  使用Ni / Cr介导的偶联反应作为关键步骤，实现了有效的抗肿瘤海洋大环内酯aplyronine A的第二代全合成。基于最长的线性序列，分38步获得的第二代aplyronine A合成途径的总产率为1.4％。与我们的第一代合成的邻苯丙氨酸A路径相比，第二代合成极大地提高了收率和步骤数。特别是，我们在C13立体中心和C14–C15（ENi / Cr介导的不对称偶联反应））-三取代双键。此外，我们为C21–C28和C29–C34之间的不对称Ni / Cr介导的偶联反应建立了有效的反应条件。因此，该偶联反应以各链段的等摩尔比进行。
• Structure–activity relationship studies on an antitumor marine macrolide using aplyronine a–swinholide A hybrid
  作者：Takayuki Ohyoshi、Atsuhiro Takano、Imari Kikuchi、Tomotaka Ogura、Mayu Namiki、Yuto Miyazaki、Takahiro Hirano、Shota Konishi、Yuta Ebihara、Koichi Takeno、Ichiro Hayakawa、Hideo Kigoshi

  DOI：10.1039/d2ob00118g

  日期：——

  An aplyronine A–swinholide A hybrid, consisting of the macrolactone part of aplyronine A and the side chain part of swinholide A, was designed, synthesized, and biologically evaluated. This hybrid induced protein–protein interactions between two major cytoskeletal proteins actin and tubulin in the same manner as aplyronine A, and exhibited potent cytotoxicity and actin-depolymerizing activity. The

  设计、合成和生物学评估了由 alyronine A 的大环内酯部分和 swinholide A 的侧链部分组成的 alyronine A-swinholide A 杂化物。这种杂合体以与 alyronine A 相同的方式诱导两种主要细胞骨架蛋白肌动蛋白和微管蛋白之间的蛋白质相互作用，并表现出强大的细胞毒性和肌动蛋白解聚活性。N、N、O中甲氧基的重要性-三甲基丝氨酸酯通过使用杂合类似物的氨基酸部分的构效关系研究得到澄清。此外，比较 alyronine A 和 swinholide A 的侧链类似物的肌动蛋白解聚活性表明，swinholide A 的侧链类似物的肌动蛋白解聚活性比 alyronine A 弱得多。
• Design, Synthesis, and Biological Evaluations of Aplyronine A–Mycalolide B Hybrid Compound
  作者：Kenichi Kobayashi、Yusuke Fujii、Yuichiro Hirayama、Shinichi Kobayashi、Ichiro Hayakawa、Hideo Kigoshi

  DOI：10.1021/ol300182r

  日期：2012.3.2

  A hybrid compound consisting of aplyronine A and mycalolide B was synthesized, and its biological activities were evaluated. The hybrid compound was found to have somewhat more potent actin-depolymerizing activity than aplyronine A. In contrast, the hybrid compound possessed about 1000-fold less cytotoxicity than aplyronine A. These results indicated that there is no direct correlation between actin-depolymerizing activity and cytotoxicity.