(S)-1-(4-((2S,3S,4E,6E,8S,9R,11E,13Z,15Z,17S,18S,19E,22E)-18-(tert-butyldimethylsilyloxy)-8-methoxy-3,7,9,13,15,17,20,23-octamethyl-10,24-dioxooxacyclotetracosa-4,6,11,13,15,19,22-heptaen-2-yl)thiazol-2-yl)-3-methylbutyl methylcarbamate | 934828-71-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (S)-1-(4-((2S,3S,4E,6E,8S,9R,11E,13Z,15Z,17S,18S,19E,22E)-18-(tert-butyldimethylsilyloxy)-8-methoxy-3,7,9,13,15,17,20,23-octamethyl-10,24-dioxooxacyclotetracosa-4,6,11,13,15,19,22-heptaen-2-yl)thiazol-2-yl)-3-methylbutyl methylcarbamate
• 英文别名: [(1S)-1-[4-[(2S,3S,4E,6E,8S,9R,11E,13Z,15Z,17S,18S,19E,22E)-18-[tert-butyl(dimethyl)silyl]oxy-8-methoxy-3,7,9,13,15,17,20,23-octamethyl-10,24-dioxo-1-oxacyclotetracosa-4,6,11,13,15,19,22-heptaen-2-yl]-1,3-thiazol-2-yl]-3-methylbutyl] N-methylcarbamate
• CAS: 934828-71-4
• 化学式: C₄₈H₇₄N₂O₇SSi
• 分子量: 851.276
• InChiKey: UAGRMKLSXDVBKE-OPQSAORDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.3
• 重原子数：
  59
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-1-(4-((2S,3S,4E,6E,8S,9R,11E,13Z,15Z,17S,18S,19E,22E)-18-(tert-butyldimethylsilyloxy)-8-methoxy-3,7,9,13,15,17,20,23-octamethyl-10,24-dioxooxacyclotetracosa-4,6,11,13,15,19,22-heptaen-2-yl)thiazol-2-yl)-3-methylbutyl methylcarbamate 在 吡啶 、 dimethyl sulfide borane 、 氢氟酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 1.0h， 生成 archazolid A
  参考文献：
  名称：

  Total Synthesis of Archazolid A

  摘要：

  The archazolids are complex polyketides isolated from the myxobacterium Archangium gephyra and are potent inhibitors of vacuolar type ATPases. Herein, we report the first total synthesis of archazolid A, which establishes unequivocally the relative and absolute configuration of this macrolide antibiotic. Key features of our synthesis include an aldol condensation for construction of the delicate (Z,Z,E)-triene-system, an E-selective Heck reaction on a highly elaborate substrate, and a HWE macrocyclization to close the 24-membered macrolactone.

  DOI：

  10.1021/ja071461o
• 作为产物：
  描述：

  在 sodium hydride 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (S)-1-(4-((2S,3S,4E,6E,8S,9R,11E,13Z,15Z,17S,18S,19E,22E)-18-(tert-butyldimethylsilyloxy)-8-methoxy-3,7,9,13,15,17,20,23-octamethyl-10,24-dioxooxacyclotetracosa-4,6,11,13,15,19,22-heptaen-2-yl)thiazol-2-yl)-3-methylbutyl methylcarbamate
  参考文献：
  名称：

  Total Synthesis of Archazolid A

  摘要：

  The archazolids are complex polyketides isolated from the myxobacterium Archangium gephyra and are potent inhibitors of vacuolar type ATPases. Herein, we report the first total synthesis of archazolid A, which establishes unequivocally the relative and absolute configuration of this macrolide antibiotic. Key features of our synthesis include an aldol condensation for construction of the delicate (Z,Z,E)-triene-system, an E-selective Heck reaction on a highly elaborate substrate, and a HWE macrocyclization to close the 24-membered macrolactone.

  DOI：

  10.1021/ja071461o

文献信息

• Modular Total Synthesis of Archazolid A and B
  作者：Dirk Menche、Jorma Hassfeld、Jun Li、Kerstin Mayer、Sven Rudolph

  DOI：10.1021/jo901565n

  日期：2009.10.2

  of highly elaborate intermediates. For macrocyclization, both an HWE reaction and a Heck coupling were successfully employed to close the 24-membered macrolactone. During the synthetic campaign, a generally useful protocol for an E-selective Heck reaction of nonactivated alkenes and a method for the direct nucleophilic displacement of the Abiko−Masamune auxiliary with sterically hindered nucleophiles

  报告了有效的V-ATPase抑制剂archazolid A和B的模块化全合成。汇合的准备工作是通过联合中间体的后期多样化来完成的。关键的合成步骤涉及不对称的硼介导的羟醛反应，两个连续的Still-Gennari烯烃化反应以设定特征性（Z，Z）-二烯系统，布朗crotyboration和非对映选择性的高度精制中间体的羟醛缩合。对于大环化，HWE反应和Heck偶联均成功用于封闭24元大环内酯。在合成运动期间，对于E而言，通常有用的协议开发了非活化烯烃的选择性Heck反应和具有空间受阻亲核试剂的Abiko-MaSAmune助剂直接亲核取代的方法。方便而灵活的策略将使对拟唑的进一步SAR研究和对靶标与抑制剂相互作用的更详细评估成为可能。
• Design, synthesis, and biological evaluation of novel analogues of archazolid: A highly potent simplified V-ATPase inhibitor
  作者：Dirk Menche、Jorma Hassfeld、Florenz Sasse、Markus Huss、Helmut Wieczorek

  DOI：10.1016/j.bmcl.2006.12.073

  日期：2007.3

  Novel analogues of the V-ATPase inhibitors archazolid A and B with modifications of the free hydroxyl groups and the side chain were designed by molecular modeling, synthesized by derivatization of the parent natural product and evaluated for V-ATPase inhibition and growth inhibition of murine connective tissue cells. (c) 2006 Elsevier Ltd. All rights reserved.