(-)-曲古柳菌素A | 122292-85-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (-)-曲古柳菌素A
• 英文名称: (S)-(-)-trichostatin A
• 英文别名: (S)-trichostatin A；trichostatin A；(-)-TSA；(S)-TSA；TSA；S-Trichostatin A；(2E,4E,6S)-7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide
• CAS: 122292-85-7
• 化学式: C₁₇H₂₂N₂O₃
• 分子量: 302.373
• InChiKey: RTKIYFITIVXBLE-LEJRBOCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  温度低于0°C时，请避免加热。

制备方法与用途

(S)-Trichostatin A ((S)-TSA) 是一种选择性 HDAC6 抑制剂，对斑马鱼和人的 HDAC6 的 IC50 值分别为 9.88 nM 和 11.1 nM。(S)-Trichostatin A 对其他 HDAC 的抑制作用较弱。

反应信息

• 作为产物：
  描述：

  (R)-曲古抑菌酸 在 Amberlyst 15 、 氯甲酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.08h， 生成 (-)-曲古柳菌素A
  参考文献：
  名称：

  Synthesis of trichostatin a, a potent differentiation inducer of friend leukemic cells, and its antipode

  摘要：

  DOI：

  10.1016/s0040-4020(01)89789-1

文献信息

• Evolution of Concise and Flexible Synthetic Strategies for Trichostatic Acid and the Potent Histone Deacetylase Inhibitor Trichostatin A
  作者：Casey C. Cosner、Vijaya Bhaskara Reddy Iska、Anamitra Chatterjee、John T. Markiewicz、Steven J. Corden、Joakim Löfstedt、Tobias Ankner、Joshua Richer、Tyler Hulett、Douglas J. Schauer、Olaf Wiest、Paul Helquist

  DOI：10.1002/ejoc.201201233

  日期：2013.1

  enantioenriched forms. Three independent synthetic pathways were developed with varying degrees of efficiency and convergency. In the first synthesis, the key step was a vinylogous Horner-Wadsworth-Emmons condensation. A Marshall propargylation reaction was used as the key step in the second synthesis, and Pd-catalyzed a-alkenylation of a ketone zinc enolate by using various functionalized alkenyl or

  (R)-(+)-Trichostatic acid 和 (R)-(+)-曲古抑菌素 A (TSA) 是在表观遗传治疗领域引起广泛关注的天然产物。特别是 TSA 是一种天然存在的异羟肟酸，具有作为组蛋白脱乙酰酶抑制剂 (HDACi) 的有效活性，并具有治疗多种遗传疾病的巨大潜力。由于这些化合物的天然丰度低和成本高，将 TSA 和其他固管酸衍生物开发成有用的小分子疗法一直受到阻碍。我们在此报告了我们在开发用于合成外消旋和对映体富集形式的脱发酸和 TSA 的简洁且可扩展的路线方面的集体努力。开发了三种独立的合成途径，具有不同程度的效率和收敛性。在第一个合成中，关键步骤是一个带有乙烯基的 Horner-Wadsworth-Emmons 缩合。马歇尔炔丙基化反应被用作第二次合成中的关键步骤，并且通过使用各种官能化的烯基或二烯基卤化物开发了 Pd 催化的酮烯醇锌的α-烯基化用于第三次合成。事实证明，第
• [EN] QUINOLINYL-PYRAZINE-CARBOXAMIDE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS DE QUINOLINYL-PYRAZINE-CARBOXAMIDE ET UTILISATIONS ASSOCIÉES
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2020132459A1

  公开（公告）日：2020-06-25

  This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinolinyl-pyrazine-carboxamide (or similar) structure which function as activators of the cholesterol biosynthesis pathway within cancer cells and/or immune cells, which function as activators of the cell cycle regulation pathway within cancer cells and/or immune cells, and which function as up-regulators of HMGCS1 protein expression within cancer cells and/or immune cells, and which function as effective therapeutic agents for treating, ameliorating, and preventing various forms of cancer and other inflammatory disease.

  这项发明属于药物化学领域。具体来说，该发明涉及一类新型小分子，其具有喹啉基-吡嗪-羧酰胺（或类似）结构，其在癌细胞和/或免疫细胞内作为胆固醇生物合成途径的激活剂，作为癌细胞和/或免疫细胞内细胞周期调控途径的激活剂，作为癌细胞和/或免疫细胞内HMGCS1蛋白表达的上调剂，以及作为治疗、改善和预防各种癌症和其他炎症性疾病的有效治疗剂。
• SYNTHESIS, OF TRICHOSTATIN A. A POTENT DIFFERENTIATION INDUCER OF FRIEND +, TETRAHEDRON, 44,(1988) N 19, C. 6013-6020
  作者：SYNTHESIS, OF TRICHOSTATIN A. A POTENT DIFFERENTIATION INDUCER OF FRIEND +

  DOI：——

  日期：——
• [EN] STRUCTURE-BASED MODELING AND TARGET-SELECTIVITY PREDICTION<br/>[FR] MODÉLISATION BASÉE SUR LA STRUCTURE ET PRÉDICTION DE SÉLECTIVITÉ CIBLE
  申请人：EPIGENETX LLC

  公开号：WO2015002860A1

  公开（公告）日：2015-01-08

  The present invention provides, inter alia, methods, models, and systems for selecting an effector having specificity for a target molecule. The methods and systems of the present invention involve several steps, including compiling a database containing structural data for a library of molecules and a population of ligands and activity data, establishing structure-based equivalence of sequence elements in the library of molecules, determining likely spatial orientations of population ligands in library molecules, calculating interaction energies for each ligand-molecule pair, generating statistical models that are predictive of sequence elements likely to contribute to a differential effect of ligands on molecules, selecting an effector that is likely to have a desired specificity for the target molecule, experimentally determining activity data for effector-library molecule pairs, and at least once repeating the steps listed above wherein the effector is a member of the population of ligands.
• Synthesis of trichostatin a, a potent differentiation inducer of friend leukemic cells, and its antipode
  作者：Kenji Mori、Koshi Koseki

  DOI：10.1016/s0040-4020(01)89789-1

  日期：1988.1