3-{(2S,5S)-5-[2-((2S,4R,6R)-6-{[(2S,3S,4R,5R)-3-[(1RS)-3-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tertbutyl(dimethyl)silyl]oxy}-6-((1S,2E)-1-{[tert-butyl(dimethyl)silyl]oxy}-3-iodoprop-2-en-1-yl)octahydropyrano[3,2-b]pyran-2-yl]-2-oxo-propyl]-5-((2S)-2,3-bis{[tertbutyl(dimethyl)silyl]oxy}propyl)-4-methoxytetrahydrofuran-2-yl]methyl}-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylenetetrahydrofuran-2-yl}propanal | 253128-06-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-{(2S,5S)-5-[2-((2S,4R,6R)-6-{[(2S,3S,4R,5R)-3-[(1RS)-3-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tertbutyl(dimethyl)silyl]oxy}-6-((1S,2E)-1-{[tert-butyl(dimethyl)silyl]oxy}-3-iodoprop-2-en-1-yl)octahydropyrano[3,2-b]pyran-2-yl]-2-oxo-propyl]-5-((2S)-2,3-bis{[tertbutyl(dimethyl)silyl]oxy}propyl)-4-methoxytetrahydrofuran-2-yl]methyl}-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylenetetrahydrofuran-2-yl}propanal
• 英文别名: 3-[(2S,5S)-5-[2-[(2S,4R,6R)-6-[[(2S,3S,4R,5R)-3-[3-[(2S,3R,4S,4aS,6R,8aS)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-2-[(E,1S)-1-[tert-butyl(dimethyl)silyl]oxy-3-iodoprop-2-enyl]-2,3,4,4a,6,7,8,8a-octahydropyrano[3,2-b]pyran-6-yl]-2-oxopropyl]-5-[(2S)-2,3-bis[[tert-butyl(dimethyl)silyl]oxy]propyl]-4-methoxyoxolan-2-yl]methyl]-4-methyl-5-methylideneoxan-2-yl]ethyl]-4-methylideneoxolan-2-yl]propanal
• CAS: 253128-06-2
• 化学式: C₇₀H₁₃₁IO₁₃Si₅
• 分子量: 1448.13
• InChiKey: UOOJKQYWSCHIGR-DSCADUBNSA-N

物化性质

• 沸点：
  984.0±65.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  18.18
• 重原子数：
  89
• 可旋转键数：
  33
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  136
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  3-{(2S,5S)-5-[2-((2S,4R,6R)-6-{[(2S,3S,4R,5R)-3-[(1RS)-3-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tertbutyl(dimethyl)silyl]oxy}-6-((1S,2E)-1-{[tert-butyl(dimethyl)silyl]oxy}-3-iodoprop-2-en-1-yl)octahydropyrano[3,2-b]pyran-2-yl]-2-oxo-propyl]-5-((2S)-2,3-bis{[tertbutyl(dimethyl)silyl]oxy}propyl)-4-methoxytetrahydrofuran-2-yl]methyl}-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylenetetrahydrofuran-2-yl}propanal 在 chromium dichloride 、 戴斯-马丁氧化剂 、 nickel dichloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1R,3S,5R,6R,7S,11R,14S,15S,16S,17R,18S,19S,20E,22RS,25S,28S,31S,33R)-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-16,17,19-tris{[tert-butyl(dimethyl)silyl]oxy}-22-hydroxy-6-methoxy-33-methyl-27,34-bis(methylene)-4,35,36,37,38-pentaoxahexacyclo[29.3.1.111,15.114,18.125,28.03,7]octatriacont-20-en-9-one
  参考文献：
  名称：

  Macrocyclic ketone analogues of halichondrin B

  摘要：

  Structurally simplified macrocyclic ketone analogues of halichondrin B were prepared by total synthesis and found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.069
• 作为产物：
  描述：

  3-{(2S,5S)-5-[2-((2S,4R,6R)-6-{[(2S,3S,4R,5R)-3-[(1RS)-3-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tertbutyl(dimethyl)silyl]oxy}-6-((1S,2E)-1-{[tert-butyl(dimethyl)silyl]oxy}-3-iodoprop-2-en-1-yl)octahydropyrano[3,2-b]pyran-2-yl]-2-oxo-1-(phenylsulfonyl)propyl]-5-((2S)-2,3-bis{[tertbutyl(dimethyl)silyl]oxy}propyl)-4-methoxytetrahydrofuran-2-yl]methyl}-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylenetetrahydrofuran-2-yl}propanal 在 samarium diiodide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以82%的产率得到3-{(2S,5S)-5-[2-((2S,4R,6R)-6-{[(2S,3S,4R,5R)-3-[(1RS)-3-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tertbutyl(dimethyl)silyl]oxy}-6-((1S,2E)-1-{[tert-butyl(dimethyl)silyl]oxy}-3-iodoprop-2-en-1-yl)octahydropyrano[3,2-b]pyran-2-yl]-2-oxo-propyl]-5-((2S)-2,3-bis{[tertbutyl(dimethyl)silyl]oxy}propyl)-4-methoxytetrahydrofuran-2-yl]methyl}-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylenetetrahydrofuran-2-yl}propanal
  参考文献：
  名称：

  Macrocyclic ketone analogues of halichondrin B

  摘要：

  Structurally simplified macrocyclic ketone analogues of halichondrin B were prepared by total synthesis and found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.069

文献信息

• Commercial Manufacture of Halaven®: Chemoselective Transformations En Route to Structurally Complex Macrocyclic Ketones
  作者：Francis Fang、Brian Austad、Trevor Calkins、Charles Chase、Thomas Horstmann、Yongbo Hu、Bryan Lewis、Xiang Niu、Thomas Noland、John Orr、Matthew Schnaderbeck、Huiming Zhang、Naoki Asakawa、Naoki Asai、Hiroyuki Chiba、Takashi Hasebe、Yorihisa Hoshino、Hiroyuki Ishizuka、Takashi Kajima、Akio Kayano、Yuki Komatsu、Manabu Kubota、Hirofumi Kuroda、Mamoru Miyazawa、Katsuya Tagami、Tomohiro Watanabe

  DOI：10.1055/s-0032-1318026

  日期：——

  The evolution of the synthesis of Halaven (R) (E7389, INN eribulin mesylate) from a medicinal chemistry process to the execution of the final process on pilot scale is described. The completion of the synthesis of Halaven (R) from C1-C13 ester and C14-C35 sulfone alcohol involves a series of chemo-, regio-, and stereoselective transformations. Furthermore, a high-dilution macrocyclization presented a number of challenges for industrial-scale manufacture (throughput, processing time, and side reactions). This paper describes studies at Eisai leading to an understanding, optimization, and control of the chemistry that realized the reproducible commercial production of Halaven (R).