(4S,7R,8S,9S,16S)-4,8-bis((tert-butyldimethylsilyl)oxy)-5,5,7,9,13-pentamethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)oxacyclohexadec-13-ene-2,6-dione | 204195-20-0

• 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: (4S,7R,8S,9S,16S)-4,8-bis((tert-butyldimethylsilyl)oxy)-5,5,7,9,13-pentamethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)oxacyclohexadec-13-ene-2,6-dione
• CAS: 204195-20-0
• 化学式: C₃₉H₆₉NO₅SSi₂
• 分子量: 720.218
• InChiKey: BIYYEQKEADNAJH-XBQVACHMSA-N

物化性质

• 沸点：
  698.1±55.0 °C(Predicted)
• 密度：
  1.01±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  11.33
• 重原子数：
  48.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  74.72
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (4S,7R,8S,9S,16S)-4,8-bis((tert-butyldimethylsilyl)oxy)-5,5,7,9,13-pentamethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)oxacyclohexadec-13-ene-2,6-dione 在 二甲基二环氧乙烷 、 氟化氢吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 4.0h， 生成 埃博霉素B
  参考文献：
  名称：

  Total Syntheses of Epothilones A and B

  摘要：

  Convergent, stereocontrolled total syntheses of the microtubule-stabilizing macrolides epothilones A (2) and B (3) have been achieved. Four distinct ring-forming strategies were pursued (see Scheme 1). Of these four, three were reduced to practice. In one approach, the action of a base on a substance possessing an acetate ester and a nonenolizable aldehyde brought about a remarkably effective macroaldolization see (89 --> 90 + 91; 99 --> 100 + 101), simultaneously creating the C2-C3 bond and the hydroxyl-bearing stereocenter at C-3. Alternatively, the 16-membered macrolide of the epothilones could be fashioned through a C12-C13 ring-closing olefin metathesis (e.g. see 111 --> 90 + 117; 122 --> 105 + 123) and through macrolactonization of the appropriate hydroxy acid (e.g. see 88 --> 93). The application of a stereospecific B-alkyl Suzuki coupling strategy permitted the establishment of a cis C12-C13 olefin, thus setting the stage for an eventual site-and diastereoselective epoxidation reaction (see 96 --> 2; 106 --> 3). The development of a novel cyclopropane solvolysis strategy for incorporating the geminal methyl groups of the epothilones (see 39 --> 40 --> 41), and the use of Lewis acid catalyzed diene-aldehyde cyclocondensation (LACDAC) (see 35 + 36 --> 37) and asymmetric allylation (see 10 --> 76) methodology are also noteworthy.

  DOI：

  10.1021/ja971946k
• 作为产物：
  描述：

  (1E,3Z)-1-甲氧基-2-甲基-3-(三甲基硅氧基)-1,3-戊二烯 在 [Mo(CHMe₂Ph)(N-(2,6-(i-Pr)2C₆H₃))(OCMe(CF₃)2)2] 吡啶 、 咪唑 、 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 N-碘代丁二酰亚胺 、 lithium aluminium tetrahydride 、 草酰氯 、 偶氮二异丁腈 、 camphor-10-sulfonic acid 、 叔丁基锂 、 diethylzinc 、 三正丁基氢锡 、 四氯化钛 、 戴斯-马丁氧化剂 、 氟化氢吡啶 、 di(1H-imidazol-2-yl)methanethione 、 二甲基亚砜 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 [双(三氟乙酰氧基)碘]苯 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 15.0h， 生成 (4S,7R,8S,9S,16S)-4,8-bis((tert-butyldimethylsilyl)oxy)-5,5,7,9,13-pentamethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)oxacyclohexadec-13-ene-2,6-dione
  参考文献：
  名称：

  Total Syntheses of Epothilones A and B

  摘要：

  Convergent, stereocontrolled total syntheses of the microtubule-stabilizing macrolides epothilones A (2) and B (3) have been achieved. Four distinct ring-forming strategies were pursued (see Scheme 1). Of these four, three were reduced to practice. In one approach, the action of a base on a substance possessing an acetate ester and a nonenolizable aldehyde brought about a remarkably effective macroaldolization see (89 --> 90 + 91; 99 --> 100 + 101), simultaneously creating the C2-C3 bond and the hydroxyl-bearing stereocenter at C-3. Alternatively, the 16-membered macrolide of the epothilones could be fashioned through a C12-C13 ring-closing olefin metathesis (e.g. see 111 --> 90 + 117; 122 --> 105 + 123) and through macrolactonization of the appropriate hydroxy acid (e.g. see 88 --> 93). The application of a stereospecific B-alkyl Suzuki coupling strategy permitted the establishment of a cis C12-C13 olefin, thus setting the stage for an eventual site-and diastereoselective epoxidation reaction (see 96 --> 2; 106 --> 3). The development of a novel cyclopropane solvolysis strategy for incorporating the geminal methyl groups of the epothilones (see 39 --> 40 --> 41), and the use of Lewis acid catalyzed diene-aldehyde cyclocondensation (LACDAC) (see 35 + 36 --> 37) and asymmetric allylation (see 10 --> 76) methodology are also noteworthy.

  DOI：

  10.1021/ja971946k

文献信息

• Catalytic Antibody Route to the Naturally Occurring Epothilones: Total Synthesis of Epothilones A-F
  作者：Subhash C. Sinha、Jian Sun、Gregory P. Miller、Markus Wartmann、Richard A. Lerner

  DOI：10.1002/1521-3765(20010417)7:8<1691::aid-chem16910>3.0.co;2-9

  日期：2001.4.17

  synthesized starting from enantiomerically pure aldol compounds 9-11, which were obtained by antibody catalysis. Aldolase antibody 38C2 catalyzed the resolution of (+/-)-9 by enantioselective retro-aldol reaction to afford 9 in 90% ee at 50 % conversion. Compounds 10 and 11 were obtained in more than 99% ee at 50% conversion by resolution of their racemic mixtures using newly developed aldolase antibodies

  天然存在的埃坡霉素已从对映异构纯的羟醛化合物 9-11 开始合成，这些化合物是通过抗体催化获得的。醛缩酶抗体 38C2 通过对映选择性逆醛醇反应催化 (+/-)-9 的拆分，以 50% 转化率提供 9 in 90% ee。通过使用新开发的醛缩酶抗体 84G3、85H6 或 93F3 拆分其外消旋混合物，化合物 10 和 11 的转化率为 99% 以上，转化率为 50%。化合物 9、10 和 11 以数克的量进行拆分，然后通过复分解过程转化为埃坡霉素，该过程由 Grubbs 催化剂催化。
• Rapid access to epothilone analogs via semisynthetic degradation and reconstruction of epothilone D
  作者：Steven D. Dong、Kurt Sundermann、Karen M.J. Smith、Joseph Petryka、Fenghua Liu、David C. Myles

  DOI：10.1016/j.tetlet.2003.12.123

  日期：2004.2

  A facile and efficient route to epothilone analogs has been developed from the natural product epothilone D (1). Degradation of 1 via an oxidative cleavage sequence provides acid intermediate 4 rapidly in six steps. From 4, a variety of epothilone analogs have been prepared utilizing ring-closing metathesis to reconstruct the trisubstituted-12,13-double bond. Using this approach, we report a number of epothilone analogs with varying C-15 aromatic side chains and C-14 allylic substitutions and their biological activities. (C) 2004 Elsevier Ltd. All rights reserved.