(4R,5R,9R,10S,10aS)-hexahydro-5,9,10-trihydroxy-9-methyl-4-(4-morpholinylmethyl)-8H,5,10a-(iminomethano)-6H-pyrrolo<2,1-b><1,3>oxazocine-6,11-dione | 143063-20-1

• 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: (4R,5R,9R,10S,10aS)-hexahydro-5,9,10-trihydroxy-9-methyl-4-(4-morpholinylmethyl)-8H,5,10a-(iminomethano)-6H-pyrrolo<2,1-b><1,3>oxazocine-6,11-dione
• 英文别名: (1S,2S,3S,7R,8R)-2,3,7-trihydroxy-3-methyl-8-(morpholin-4-ylmethyl)-11-oxa-5,13-diazatricyclo[5.4.2.01,5]tridecane-6,12-dione
• CAS: 143063-20-1
• 化学式: C₁₆H₂₅N₃O₇
• 分子量: 371.39
• InChiKey: ONZJRLJACZJKSH-ZEDHKUJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  bicyclomycin 3'-O-methanesulfonate 在 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 27.0h， 生成 (4R,5R,9R,10S,10aS)-hexahydro-5,9,10-trihydroxy-9-methyl-4-(4-morpholinylmethyl)-8H,5,10a-(iminomethano)-6H-pyrrolo<2,1-b><1,3>oxazocine-6,11-dione
  参考文献：
  名称：

  The synthesis and reactivity of [N(8)-C(3')]-cyclized bicyclomycin. Evidence of the role of the C(1)-triol group in bicyclomycin-mediated processes

  摘要：

  The C(1) triol group in the antibiotic, bicyclomycin (1) has been proposed to play an integral role in the bonding of key protein nucleophiles to the distal C(5)-C(5a) terminal double bond in the drug. Evidence in support of this concept has been provided by the comparison of the reactivities of bicyclomycin (1), the [N(8)-C(3')]-cyclized bicyclomycin adduct 3, 2',3'-bicyclomycin acetonide (17), and the acetonide derivative of 3, 18, with sodium ethanethiolate. Significantly, 3 displayed enhanced reactivity versus 1, 17, and 18 in this transformation. The controlling factors for the increased reactivity of 3 have been discerned and the importance of the C(1') hydroxyl group delineated. Key kinetic parameters are reported for the treatment of both 3 and 17 with 2-mercaptopyridine. Structural details are provided for both C(5a) thiolate and amine adducts of 3. The importance of these findings in relation to the mode of action of bicyclomycin are briefly discussed.

  DOI：

  10.1021/jo00045a041

文献信息

• Synthesis and reactivity of bicyclomycin C(3') amines
  作者：Hyeung-Geun Park、Marco A. Vela、Harold Kohn

  DOI：10.1021/ja00081a006

  日期：1994.1

  The novel bicyclomycin C(3') tertiary amines 6-8 were prepared in which morpholine, N-acetylpiperazine, and N-carboethoxypiperazine were installed at the C(3') site in bicyclomycin (1), respectively. Previous attempts to synthesize bicyclomycin C(3') amines were unsuccessful. Compounds 68 were found to be more reactive than 1 in neutral and basic solutions. Under these conditions, a novel ring fragmentation

  制备了新型双环霉素 C(3') 叔胺 6-8，其中吗啉、N-乙酰哌嗪和 N-carboethoxypiperazine 分别安装在双环霉素 (1) 的 C(3') 站点上。以前合成双环霉素 C(3') 胺的尝试没有成功。发现化合物 68 在中性和碱性溶液中比 1 更具反应性。在这些条件下，发生了新的环断裂过程以产生单取代的乙内酰脲（即 15、18、19）和 α-亚甲基-γ-丁内酯（17）。提出了形成乙内酰脲 15、18 和 19 以及丁内酯 17 的途径，并提供了支持这些假设的证据。讨论了这种环断裂过程在未来药物设计中的潜在意义
• The synthesis and reactivity of [N(8)-C(3')]-cyclized bicyclomycin. Evidence of the role of the C(1)-triol group in bicyclomycin-mediated processes
  作者：Marco A. Vela、Harold Kohn

  DOI：10.1021/jo00045a041

  日期：1992.9

  The C(1) triol group in the antibiotic, bicyclomycin (1) has been proposed to play an integral role in the bonding of key protein nucleophiles to the distal C(5)-C(5a) terminal double bond in the drug. Evidence in support of this concept has been provided by the comparison of the reactivities of bicyclomycin (1), the [N(8)-C(3')]-cyclized bicyclomycin adduct 3, 2',3'-bicyclomycin acetonide (17), and the acetonide derivative of 3, 18, with sodium ethanethiolate. Significantly, 3 displayed enhanced reactivity versus 1, 17, and 18 in this transformation. The controlling factors for the increased reactivity of 3 have been discerned and the importance of the C(1') hydroxyl group delineated. Key kinetic parameters are reported for the treatment of both 3 and 17 with 2-mercaptopyridine. Structural details are provided for both C(5a) thiolate and amine adducts of 3. The importance of these findings in relation to the mode of action of bicyclomycin are briefly discussed.