(2S,3E)-5-chloro-2,4-dimethyl-3-pentenoic acid | 1352449-36-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2S,3E)-5-chloro-2,4-dimethyl-3-pentenoic acid
• 英文别名: 5-chloro-2,4-dimethyl-3-pentenoic acid；(S,E)-5-Chloro-2,4-dimethylpent-3-enoic acid；(E,2S)-5-chloro-2,4-dimethylpent-3-enoic acid
• CAS: 1352449-36-5
• 化学式: C₇H₁₁ClO₂
• 分子量: 162.616
• InChiKey: VCJZICCGLIDMAB-QVQDZQDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S,3E)-5-chloro-2,4-dimethyl-3-pentenoic acid 、 在 N-羟基-7-氮杂苯并三氮唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  What is a “DNA-Compatible” Reaction?

  摘要：

  DNA-encoded synthesis can generate vastly diverse screening libraries of arbitrarily complex molecules as long as chemical reaction conditions do not compromise DNA's informational integrity, a fundamental constraint that "DNA-compatible" reaction development does not presently address. We devised DNA-encoded reaction rehearsal, an integrated analysis of reaction yield and impact on DNA, to acquire these key missing data. Magnetic DNA-functionalized sensor beads quantitatively report the % DNA template molecules remaining viable for PCR amplification after exposure to test reaction conditions. Analysis of solid-phase bond forming (e.g., Suzuki-Miyaura cross-coupling, reductive amination) and deprotection reactions (e.g., allyl esters, silyl ethers) guided the definition and optimization of DNA-compatible reaction conditions (>90% yield, >30% viable DNA molecules), most notably in cases that involved known (H+, Pd) and more obscure (Delta, DMF) hazards to DNA integrity. The data provide an empirical yet mechanistically consistent and predictive framework for designing successful DNA-encoded reaction sequences for combinatorial library synthesis.

  DOI：

  10.1021/acscombsci.5b00198

文献信息

• [EN] CHIRAL COMPOUNDS OF VARYING CONFORMATIONAL RIGIDITY AND METHODS OF SYNTHESIS<br/>[FR] COMPOSÉS CHIRAUX À RIGIDITÉ DE CONFORMATION VARIABLE ET LEURS PROCÉDÉS DE SYNTHÈSE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2013036753A1

  公开（公告）日：2013-03-14

  Synthesis of compounds having varying degrees of conformational rigidity is obtained via a low cost, high yield and efficient synthetic reactions. The library of compounds is structurally diverse, having at least one or more chiral centers and providing large numbers of compounds having building block diversity and substantial scaffold diversity. The compounds further provide a novel method for obtaining candidate therapeutic agents for prevention, treatment or diagnosis of diseases.

  通过低成本、高产率和高效的合成反应，可以合成具有不同程度构象刚性的化合物。这些化合物库在结构上多样，至少具有一个或多个手性中心，并提供大量具有构建块多样性和基本支架多样性的化合物。这些化合物进一步提供了一种新颖的方法，用于获得用于预防、治疗或诊断疾病的候选治疗剂。
• A biomimetic polyketide-inspired approach to small-molecule ligand discovery
  作者：Claudio Aquino、Mohosin Sarkar、Michael J. Chalmers、Kimberly Mendes、Thomas Kodadek、Glenn C. Micalizio

  DOI：10.1038/nchem.1200

  日期：2012.2

  The discovery of new compounds for the pharmacological manipulation of protein function often embraces the screening of compound collections, and it is widely recognized that natural products offer beneficial characteristics as protein ligands. Much effort has therefore been focused on ‘natural product-like’ libraries, yet the synthesis and screening of such libraries is often limited by one or more of the following: modest library sizes and structural diversity, conformational heterogeneity and the costs associated with the substantial infrastructure of modern high-throughput screening centres. Here, we describe the design and execution of an approach to this broad problem by merging principles associated with biologically inspired oligomerization and the structure of polyketide-derived natural products. A novel class of chiral and conformationally constrained oligomers is described (termed ‘chiral oligomers of pentenoic amides’, COPA), which offers compatibility with split-and-pool methods and can be screened en masse in a batch mode. We demonstrate that a COPA library containing 160,000 compounds is a useful source of novel protein ligands by identifying a non-covalent synthetic ligand to the DNA-binding domain of the p53 transcription factor. The design and synthesis of a family of chiral and conformationally constrained oligomers is described. Asymmetric synthesis of the monomers is presented and the preparation of a 160,000-member library of diverse tetramers via split-and-pool methods is discussed. From this library, a non-covalent ligand to the DNA-binding domain of p53 was discovered.

  新化合物的发现用于药理学上调控蛋白质功能，通常涉及对化合物库的筛选，广泛认为天然产物作为蛋白质配体具有有利特点。因此，许多精力集中在“天然产物类似物”库的研究上，但该类库的合成和筛选往往受到以下一项或多项因素的限制：库规模和结构多样性有限，构象异质性，以及与现代高通量筛选中心巨大的基础设施相关的成本。在这里，我们通过结合与生物启发的聚合原理及聚酮类天然产物结构相关的原则，描述了针对这一广泛问题的设计和执行方法。我们描述了一种新型的手性和构象受限的聚合物类别（称为“戊烯酰胺的手性聚合物”，COPA），该类聚合物兼容于分裂与组合的方法，并能够以批量模式进行大规模筛选。我们证明，一个包含160,000个化合物的COPA库是新型蛋白质配体的有用来源，通过识别出一个与p53转录因子DNA结合域的非共价合成配体。文中还描述了一系列手性和构象受限的聚合物的设计和合成，介绍了单体的非对称合成，以及通过分裂与组合方法制备160,000个多样四聚体的库。最终，从这个库中发现了一个与p53的DNA结合域结合的非共价配体。
• What is a “DNA-Compatible” Reaction?
  作者：Marie L. Malone、Brian M. Paegel

  DOI：10.1021/acscombsci.5b00198

  日期：2016.4.11

  DNA-encoded synthesis can generate vastly diverse screening libraries of arbitrarily complex molecules as long as chemical reaction conditions do not compromise DNA's informational integrity, a fundamental constraint that "DNA-compatible" reaction development does not presently address. We devised DNA-encoded reaction rehearsal, an integrated analysis of reaction yield and impact on DNA, to acquire these key missing data. Magnetic DNA-functionalized sensor beads quantitatively report the % DNA template molecules remaining viable for PCR amplification after exposure to test reaction conditions. Analysis of solid-phase bond forming (e.g., Suzuki-Miyaura cross-coupling, reductive amination) and deprotection reactions (e.g., allyl esters, silyl ethers) guided the definition and optimization of DNA-compatible reaction conditions (>90% yield, >30% viable DNA molecules), most notably in cases that involved known (H+, Pd) and more obscure (Delta, DMF) hazards to DNA integrity. The data provide an empirical yet mechanistically consistent and predictive framework for designing successful DNA-encoded reaction sequences for combinatorial library synthesis.