EH21A1 | 199333-57-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: EH21A1
• 英文别名: reblastatin；lebstatin；[(4E,8S,9S,10E,12S,13R,14S,16R)-13,20-dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-azabicyclo[16.3.1]docosa-1(22),4,10,18,20-pentaen-9-yl] carbamate
• CAS: 199333-57-8
• 化学式: C₂₉H₄₄N₂O₈
• 分子量: 548.677
• InChiKey: VFJOOSVDHSUNKR-DQJDZTSCSA-N

物化性质

• 熔点：
  228 °C
• 沸点：
  753.5±60.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  150
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  EH21A1 、 乙酸酐 在 吡啶 作用下， 反应 2.0h， 以68%的产率得到18-O-acetyl A1
  参考文献：
  名称：

  格尔德霉素的酚类衍生物EH21A1-A4对Hsp90抑制活性的构象意义。

  摘要：

  Hsp90是有吸引力的化疗靶标，因为它对于多种癌基因的成熟必不可少。我们描述了EH21A1-A4，从链霉菌属sp分离的格尔德霉素的酚类衍生物的构象意义。它们的天然游离结构类似于与Hsp90蛋白结合的格尔德霉素的活性形式。它们的构象特征是它们高亲和力结合的可能原因。EH21A1-A4中缺乏有毒的苯醌也增加了其作为抗肿瘤药物先导化合物的潜力。

  DOI：

  10.1016/j.bmcl.2008.01.072
• 作为产物：
  描述：

  L-谷氨酸 在 吡啶 、 咪唑 、 2,6-二甲基吡啶 、 盐酸 、 lithium hydroxide 、 copper(l) iodide 、 Schwartz's reagent 、 草酰氯 、 dimethyl sulfide borane 、 4 A molecular sieve 、 Proton-Sponge 、 氯甲酸乙酯 、 三氯化硼 、 二异丁基氢化铝 、 potassium carbonate 、 氟化氢吡啶 、 二甲基亚砜 、 三乙胺 、 N,N'-二甲基乙二胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 162.25h， 生成 EH21A1
  参考文献：
  名称：

  Total Synthesis of Reblastatin

  摘要：

  Enantioselective total synthesis of reblastatin is described. The synthesis highlights hydrozirconation, transmetalation, aldehyde addition sequence to install E-trisubstituted olefin and C7 stereocenter, and the first use of an intramolecular Buchwald-like amidation reaction to close the 19-membered macrolactam.

  DOI：

  10.1021/ja055384d

文献信息

• Macrolactams by engineered biosynthesis
  申请人：Ashley Gary W.

  公开号：US20080188450A1

  公开（公告）日：2008-08-07

  Macrolactams are made by feeding aromatic amino acids as replacement starter units to a mutant strain of the geldanamycin-producing microorganism Streptomyces hygroscopicus var. geldanus NRRL 3602, wherein the gene cluster encoding enzymes for the biosynthesis of the natural starter unit 3-amino-5-hydroxybenzoic acid has been deleted.

  大环内酰胺是通过将芳香族氨基酸作为替代起始单元供应给生产格尔达霉素的微生物链霉菌属湿生链霉菌格尔达努斯NRRL 3602的突变菌株制备的，其中编码天然起始单元3-氨基-5-羟基苯甲酸生物合成酶的基因簇已被删除。
• Total synthesis of reblastatin: convenient preparation of coupling partners and scaled assembly
  作者：Chuancai Bian、Rui Yan、Xiaoming Yu

  DOI：10.1016/j.tet.2014.03.020

  日期：2014.5

  Potentially scalable total synthesis of reblastatin was achieved based on Panek's previous study. Novel and convenient synthetic routes were developed for the known C8-C20 and C1-C7 coupling partners. The challenging C8-C20 fragment was prepared from TBS protected (S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one (6) in nine steps (20% overall yield), and the C1-C7 fragment was synthesized from commercially available 3,4,6-tri-O-acetyl-D-glucal (9) in eight steps (35% overall yield). On a larger scale, Panek's eight-step assembly of the target molecule from the two partners was also slightly modified, giving 45 mg reblastatin (19% overall yield) in the first batch synthesis. Notable feature of our study is the settlement of the C14 chirality through a diastereoselective alpha-alkylation of 6 followed by a three-step full reduction of the lactone carboxyl, making vastly available 6 a universally applicable C11-C14 synthon for benzenoid/benzoquinone ansamycins. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis of Reblastatin, Autolytimycin, and Non-Benzoquinone Analogues: Potent Inhibitors of Heat Shock Protein 90
  作者：Iwona E. Wrona、Alexander Gozman、Tony Taldone、Gabriela Chiosis、James S. Panek

  DOI：10.1021/jo1000109

  日期：2010.5.7

  A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (similar to 25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (similar to 100 nM).
• Small molecule immunopotentiators and assays for their detection
  申请人：Valiante Nicholas

  公开号：US20110104186A1

  公开（公告）日：2011-05-05

  The invention provides immunostimulatory compositions comprising a small molecule immuno-potentiator (SMIP) compound and methods of administration thereof. Also provided are methods of administering a SMIP compound in an effective amount to enhance the immune response of a subject to an antigen. Further provided are novel compositions and methods of administering SMIP compounds alone or in combination with another agent for the treatment of cancer, infectious diseases and/or allergies/asthma. In a further aspect, the invention relates generally to methods of screening for small molecule immuno-modulatory compositions.
• US7241754B2
  申请人：——

  公开号：US7241754B2

  公开（公告）日：2007-07-10