24-O-tert-butyldimethylsilyl-ascomycin | 137820-27-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 英文名称: 24-O-tert-butyldimethylsilyl-ascomycin
• 英文别名: (1R,9S,12S,13S,14S,17R,18E,21S,23S,24R,25S,27R)-14-[tert-butyl(dimethyl)silyl]oxy-17-ethyl-1-hydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone
• CAS: 137820-27-0
• 化学式: C₄₉H₈₃NO₁₂Si
• 分子量: 906.283
• InChiKey: WYEYAHGOBLVJBV-CZHLAHQJSA-N

物化性质

• 沸点：
  878.1±75.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  63
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  167
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  24-O-tert-butyldimethylsilyl-ascomycin 在 sodium periodate 、 四氧化锇 、 N-甲基吲哚酮 、 三氟甲磺酸 作用下， 以 二氯甲烷 、 环己烷 为溶剂， 生成
  参考文献：
  名称：

  C32-O-phenalkyl ether derivatives of the immunosuppressant ascomycin: a tether length study

  摘要：

  A tether length study of C32-O-phenalkyl ether derivatives of ascomycin was conducted wherein it was determined that a 2-carbon tether provides optimum in vitro immunosuppressive activity. Oxygen-bearing substituents along the 2-carbon tether can further increase the potency of this design. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00335-2
• 作为产物：
  描述：

  24-O-tert-butyldimethylsilyl-32-O-acetyl-ascomycin 在 Candida antarctica lipase 作用下， 以 辛醇 、 甲基叔丁基醚 为溶剂， 反应 100.0h， 以90%的产率得到24-O-tert-butyldimethylsilyl-ascomycin
  参考文献：
  名称：

  First chemoenzymatic synthesis of immunomodulating macrolactam pimecrolimus

  摘要：

  The preparation of pimecrolimus, a synthetic derivative of ascomycin endowed with immunomodulatory activity, requires the selective protection of 24-hydroxy group of the ascomycin, before elaboration of the 32-hydroxy group. The aim was achieved by means of two regioselective Candida antarctica lipase-catalyzed steps. The structure of the new key intermediates, 24-, 32-monoacetates, and 24,32-diacetate, was established by means of an unambiguous NMR study. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.05.066

文献信息

• Regio- and stereoselective preparation of ascomycin-d1 and FK 506-d1
  作者：Murat Acemoglu、Hendrik Andres、Thomas Moenius

  DOI：10.1002/jlcr.558

  日期：2002.4

  The immunosuppressive macrolides ascomycin 1 and FK 506 2 were stereoselectively deuteriated at C(32) using Curran's radical translocating method. Both AIBN and Et3B/O2 were tested as radical initiator for the radical translocation/reduction step with Bu3SnD as reducing agent. Despite only minor structural differences, ascomycin and FK 506 showed remarkably different behaviour under the radical translocation/reduction conditions. Higher stereoselectivities were observed with Et3B/O2 as initiator, presumably due to lower reaction temperatures applied in this case. Copyright © 2002 John Wiley & Sons, Ltd.

  免疫抑制大环内酯药物阿斯科霉素1和FK 506 2在C(32)处采用Curran的自由基转位方法进行立体选择性氘代化。测试了AIBN和Et3B/O2作为自由基引发剂，用Bu3SnD作为还原剂进行自由基转位/还原步骤。尽管仅有细微结构差异，阿斯科霉素和FK 506在自由基转位/还原条件下表现出显著不同的行为。使用Et3B/O2作为引发剂时观察到更高的立体选择性，推测是由于在这种情况下反应温度较低。© 2002 John Wiley & Sons, Ltd.
• Preparation and immunosuppressive activity of 32-(O)-acylated and 32-(O)-thioacylated analogues of ascomycin
  作者：Rene Hersperger、Walter Schuler、Gerhard Zenke

  DOI：10.1016/s0960-894x(98)00702-1

  日期：1999.1

  A series of 32-(O)-acylated and 32-(O)-thioacylated derivatives of the antibiotic ascomycin (1) have been synthesized. These readily accessible analogues exhibit potent immunosuppressive activity in vitro, as measured by an interleukin-2 reporter gene assay and the mixed lymphocyte reaction. Such molecules are expected to have a therapeutic potential in chronic inflammatory diseases of the airways

  已合成了抗生素子囊霉素（1）的一系列32-（O）-酰化和32-（O）-硫酰化的衍生物。这些易得的类似物在体外表现出有效的免疫抑制活性，如通过白介素2报道基因测定和混合淋巴细胞反应所测量。预期此类分子在气道的慢性炎性疾病如哮喘中具有治疗潜力。
• C32-amino derivatives of the immunosuppressant ascomycin
  作者：Hyun O. Ok、John L. Szumiloski、Thomas R. Beattie、Mark T. Goulet、Mary Jo Staruch、Francis J. Dumont、Matthew J. Wyvratt

  DOI：10.1016/s0960-894x(97)00409-5

  日期：1997.9

  Various C32-amino derivatives were investigated as replacements for the C32-hydroxyl group of ascomycin and its C24-deoxy analog. The syntheses of these amino derivatives and their biological evaluation are reported herein. (C) 1997 Elsevier Science Ltd.
• On the reactivity of ascomycin at the binding domain. Part 1: Liberation of the tricarbonyl portion of ascomycin
  作者：Karl Baumann、Markus Bacher、Annelaure Damont、Klemens Högenauer、Andrea Steck

  DOI：10.1016/j.tet.2003.10.045

  日期：2003.12

  Within the binding domain, ascomycin features the unusual pattern of a masked tricarbonyl moiety, which potentially allows for high structural diversity via simple isomerisation events. Herein, methodologies, allowing the liberation of the tricarbonyl unit by blocking the 14-hydroxy group are reported. (C) 2003 Elsevier Ltd. All rights reserved.
• Carbonyl to methylene conversions at the tricarbonyl-portion of ascomycin derivatives
  作者：Karl Baumann、H Knapp、G Strnadt、G Schulz、M.A Grassberger

  DOI：10.1016/s0040-4039(99)01622-6

  日期：1999.10

  Treatment of ascomycin or its O-TBDMS-derivatives with hydrogen sulfide and pyridine in dimethylformamide solution results in deoxygenation reactions at the tricarbonyl sequence of the binding domain. 9-deoxo-ascomycins (5a-c) are obtained in high yields (75-85%) together with small amounts (2-14% yield) of 10-deoxo-ascomycins (6a-c). The novel derivative 10-deoxo-ascomycin (6a) is accessible in excellent yield (85%) from the 10-amino-analog of ascomycin upon reaction with hydrogen sulfide in the absence of base. (C) 1999 Elsevier Science Ltd. All rights reserved.