(+)-trichostatic acid | 114127-17-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (+)-trichostatic acid
• 英文别名: Trichostatic acid；(2E,4E)-7-[4-(dimethylamino)phenyl]-4,6-dimethyl-7-oxohepta-2,4-dienoic acid
• CAS: 114127-17-2
• 化学式: C₁₇H₂₁NO₃
• 分子量: 287.359
• InChiKey: VKEITMNFEJHFCX-WKWSCTOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 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：
  57.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-trichostatic acid 、 氯甲酸乙酯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  An Efficient Synthesis of (±)-Trichostatic Acid and Analogues: A New Route to (±)-Trichostatin A

  摘要：

  An efficient synthesis of rac-trichostatic acid (1) and its analogues Is reported starting from a commercially available aldehyde. Further manipulations of rac-1 led to rac-trichostatin A (TSA). Construction of the desired molecular architecture entails a two-component union, achieved through an in situ hydroboration followed by a Suzuki-Miyaura coupling with 2. The requisite homopropargyl alcohol was synthesized by exploiting allenylindium chemistry. This new protocol paved the way for the synthesis of analogues of trichostatic acid and hence TSA.

  DOI：

  10.1021/ol9029116
• 作为产物：
  描述：

  (2E,4E)-7-[4-(dimethylamino)phenyl]-7-methoxy-4,6-dimethylhepta-2,4-dienoic acid 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.25h， 以94%的产率得到(+)-trichostatic acid
  参考文献：
  名称：

  An Efficient Synthesis of (±)-Trichostatic Acid and Analogues: A New Route to (±)-Trichostatin A

  摘要：

  An efficient synthesis of rac-trichostatic acid (1) and its analogues Is reported starting from a commercially available aldehyde. Further manipulations of rac-1 led to rac-trichostatin A (TSA). Construction of the desired molecular architecture entails a two-component union, achieved through an in situ hydroboration followed by a Suzuki-Miyaura coupling with 2. The requisite homopropargyl alcohol was synthesized by exploiting allenylindium chemistry. This new protocol paved the way for the synthesis of analogues of trichostatic acid and hence TSA.

  DOI：

  10.1021/ol9029116

文献信息

• SYNTHESIS OF HDAC INHIBITORS: TRICHOSTATIN A AND ANALOGUES
  申请人：Helquist Paul

  公开号：US20110237832A1

  公开（公告）日：2011-09-29

  Embodiments herein relate to histone deacetylaces (HDACs) and HDAC inhibitors, such as trichostatin A (TSA) and TSA analogues. Embodiments provide simple methods of synthesizing TSA and TSA analogues. These methods provide routes of synthesis of TSA and TSA analogues that enable the production of the HDAC inhibitors at lower cost and in greater quantities than previously were available.

  本文涉及组蛋白去乙酰化酶（HDACs）和HDAC抑制剂，如三氯乙酸（TSA）及其类似物。实施例提供了合成TSA和TSA类似物的简单方法。这些方法提供了合成TSA和TSA类似物的途径，使得生产HDAC抑制剂的成本更低、数量更大，比以往更容易获得。
• Processes and compounds for preparing histone deacetylase inhibitors and intermediates thereof
  申请人：Helquist Paul

  公开号：US20070021612A1

  公开（公告）日：2007-01-25

  Processes for preparing unsaturated esters useful as intermediates for HDAC inhibitors, by reacting an aldehyde or ketone with compounds having the following formula XX: wherein R 8 is an aliphatic group, an aromatic group, or a combined aliphatic and aromatic group; R 9 and R 10 are each independently hydrogen, an aliphatic group, an aromatic group, a combined aliphatic and aromatic group, or R 10 forms a double bond with L 2 or X 3 ; R 11 and R 12 are each independently an aliphatic group, an aromatic group, or a combined aliphatic and aromatic group; L 2 is an aliphatic linking group, an aromatic linking group, or a combined aliphatic and aromatic linking group; A is P or As; L 2 being selected so that the number of carbon atoms directly in the carbon chain between the R 8 and R 9 groups is at least 4, X 1 and X 2 are each independently O or a single bond, and X 3 is O or forms R 13 and double bond with R 10 , wherein R 13 is an aliphatic group, an aromatic group, or a combined aliphatic and aromatic group.

  制备作为HDAC抑制剂中间体的不饱和酯的过程，通过将醛或酮与具有以下公式XX的化合物反应：其中R8是脂肪基，芳香基或脂肪基和芳香基的组合；R9和R10分别独立地是氢，脂肪基，芳香基，脂肪基和芳香基的组合，或者R10与L2或X3形成双键；R11和R12分别独立地是脂肪基，芳香基或脂肪基和芳香基的组合；L2是脂肪连接基，芳香连接基或脂肪基和芳香基连接基的组合；A是P或As；选择L2使得R8和R9之间的碳链上直接的碳原子数至少为4，X1和X2分别是O或单键，X3是O或与R10形成R13和双键，其中R13是脂肪基，芳香基或脂肪基和芳香基的组合。
• COMPOUNDS AND USES THEREOF
  申请人：Aboagye Eric Ofori

  公开号：US20100063144A1

  公开（公告）日：2010-03-11

  There is provided a compound of formula (I) wherein R 1a , R 2a , R 3 , X 1 to X 6 , a, b and c have meanings given in the description, which compounds are useful as, or are useful as prodrugs of, inhibitors of HDAC enzyme activity, and thus, in particular, in the treatment of conditions where inhibition of HDAC enzyme activity is required.

  提供了一种化合物，其分子式为(I)，其中R1a，R2a，R3，X1至X6，a，b和c的含义在描述中给出，这些化合物可用作HDAC酶活性的抑制剂，或者可用作其前药，因此特别适用于需要抑制HDAC酶活性的疾病的治疗。
• Processes and host cells for genome, pathway, and biomolecular engineering
  申请人：enEvolv, Inc.

  公开号：US10370654B2

  公开（公告）日：2019-08-06

  The present disclosure provides compositions and methods for genomic engineering.

  本公开提供了基因组工程的组合物和方法。
• Concise, Convergent Syntheses of (±)-Trichostatin A Utilizing a Pd-Catalyzed Ketone Enolate α-Alkenylation Reaction
  作者：Casey C. Cosner、Paul Helquist

  DOI：10.1021/ol200964m

  日期：2011.7.15

  Two concise, convergent syntheses of (+/-)-trichostatin A (1), a potent histone deacetylase inhibitor, have been accomplished. The key step in both is a Pd-catalyzed alpha-alkenylation reaction between ketone 2 and either dienyl bromide 3 or alkenyl bromide 9 using a modification of cross-coupling conditions described by Negishi and Hartwig. A brief investigation has shown the potential utility of a Ni-catalyzed version of this reaction. The overall synthetic routes are short and amenable to scaleup, providing access to trichostatin A via trichostatic acid as a direct precursor.