(+/-)-(1RS,2SR,6RS,7SR)-(3,5-dioxo-4,10-dioxatricyclo[5.2.1.0^2,6]dec-8-en-1-yl)methyl acetate | 6331-95-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (+/-)-(1RS,2SR,6RS,7SR)-(3,5-dioxo-4,10-dioxatricyclo[5.2.1.0^2,6]dec-8-en-1-yl)methyl acetate
• 英文别名: 1-acetoxymethyl-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride；(+/-)-1-acetoxymethyl-7-oxa-norborn-5-ene-2exo,3exo-dicarboxylic acid-anhydride；(+/-)-1-Acetoxymethyl-7-oxa-norborn-5-en-2exo,3exo-dicarbonsaeure-anhydrid；[(1R,2S,6R,7S)-3,5-dioxo-4,10-dioxatricyclo[5.2.1.02,6]dec-8-en-1-yl]methyl acetate
• CAS: 6331-95-9；19308-92-0
• 化学式: C₁₁H₁₀O₆
• 分子量: 238.197
• InChiKey: PWPCMSHKWATZRS-SDCKUUTBSA-N

物化性质

• 沸点：
  414.0±45.0 °C(Predicted)
• 密度：
  1.487±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-(1RS,2SR,6RS,7SR)-(3,5-dioxo-4,10-dioxatricyclo[5.2.1.0^2,6]dec-8-en-1-yl)methyl acetate 在 Pd-BaSO₄ 、 丙酮 作用下， 生成 1-acetoxymethyl-7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride
  参考文献：
  名称：

  Sefirow et al., Zhurnal Obshchei Khimii, 1966, vol. 36, p. 1897,1898; engl. Ausg. S. 1889, 1890

  摘要：

  DOI：
• 作为产物：
  描述：

  糠醇 在 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 116.0h， 生成 (+/-)-(1RS,2SR,6RS,7SR)-(3,5-dioxo-4,10-dioxatricyclo[5.2.1.0^2,6]dec-8-en-1-yl)methyl acetate
  参考文献：
  名称：

  Structure-Based Design of a Highly Selective Catalytic Site-Directed Inhibitor of Ser/Thr Protein Phosphatase 2B (Calcineurin)

  摘要：

  Protein serine/threonine phosphatases (PP1, PP2A and PP2B) play important roles in intracellular signal transcluctions. The immunosuppressant drugs FK506 and cyclosporin A (CsA) bind to immunophilins, and these complexes selectively inhibit PP2B (calcineurin), leading to the suppression of T-cell proliferation. Both FK506 and CsA must, however, form complexes with immunophilins to exert their inhibitory action on PP2B. Thus, it is of interest to find a direct and selective inhibitor of PP2B that does not involve the immunophilins as a biological tool for studies of PP2B and also as a candidate therapeutic agent. We selected the simple natural product cantharidin, a known PP2A-selective inhibitor, as a lead compound for this project. Primary SAR indicated that norcantharidin (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride) inhibits not only PP1 and PP2A but also PP2B, and a binding model of norcantharidin carboxylate to the PP2B catalytic site was computationally constructed. Based on this binding model, we designed and synthesized several cantharidin derivatives. Among these compounds, 1, 5-dibenzoyloxymethyl-substituted norcantharidin was found to inhibit PP2B without inhibiting PP1 or PP2A. To our knowledge, this is the first highly selective catalytic site-directed inhibitor of PP2B.

  DOI：

  10.1021/ja034694y

文献信息

• 7-Oxanorbornane and Norbornane Mimics of a Distortedβ-D-Mannopyranoside: Synthesis and Evaluation asβ-Mannosidase Inhibitors
  作者：Stephan Buser、Andrea Vasella

  DOI：10.1002/hlca.200590255

  日期：2005.12

  β-mannosidase was hardly inhibited by 3, 4, 42, 45, and 46. Only the amino triol 5 proved a stronger inhibitor. The inhibition by 5 depends on the pH value (at pH 3.5: Ki = 1900 μM; at pH 4.5: Ki = 340 μm; at pH 5.5: Ki = 110 μm). The results illustrate the strong dependence of the inhibition by bicyclic mimics upon the precise geometry and orientation of the amino group as determined by the scaffold. It

  外消旋7- oxanorbornanyl和降冰片烷基氨基醇3，4，42，45，和46被合成并作为蜗牛测试β甘露糖苷酶抑制剂。氨基四醇3由已知的丙烯酸磺酰基酯9和呋喃10获得。酯化作用使11发生了对7-氧杂降冰片烯的分子内Diels-Alder反应12。将12还原为13，进行磺酰化，异亚丙基化和顺式-二羟基化反应，得到16。第二次异丙基亚丙基化为17然后再进行脱苄基反应和Mitsunobu-Gabriel反应，得到19个通过20至3脱保护的保护基。Diels-Alder将糠酸乙酸酯和马来酸酐环加成21，然后将酸酐进行醇化，顺式-二羟基化，异丙基化和Barton脱羧，得到酯25。脱乙酰基化为26，Mitsunobu-Gabriel反应导致27转化为N- Boc类似物29，还原为醇30，并取消保护到4。1-氨基降冰片烷5获自Thiele 's Acid 31。通过二酯32的热解，所得酸酐33的甲
• Diels; Alder, Justus Liebigs Annalen der Chemie, 1931, vol. 490, p. 257,263
  作者：Diels、Alder

  DOI：——

  日期：——
• Murakami; Suzuki, Memoirs of the Institute of Scientific and Industrial Research, Osaka University, 1958, vol. 15, p. 191
  作者：Murakami、Suzuki

  DOI：——

  日期：——
• Structure-activity relationship of cantharidin derivatives to protein phosphatases 1, 2A1, and 2B
  作者：Mikiko Sodeoka、Yoshiyasu Baba、Satoko Kobayashi、Nozomu Hirukawa

  DOI：10.1016/s0960-894x(97)00316-8

  日期：1997.7

  The effects of structural modification of cantharidin on the inhibition of protein Ser/Thr phosphatases are described. Removal of the methyl substituents at C2 and C3 in cantharidin improved the inhibition of PP2B. In contrast, introduction of a substituent to C1/C4-position drastically decreased inhibition of PP1 and PP2A(1). PP2B was found to be quite tolerant to modifications at the C5 position. (C) 1997 Elsevier Science Ltd.
• Plasticizers
  申请人：KAY FRIES CHEMICALS INC

  公开号：US02406657A1

  公开（公告）日：1946-08-27