3-{(2S,5S)-5-[2-((2S,4R,6R)-6-{[(2S,3S,4R,5R)-3-[(1RS,2RS)-3-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tert-butyl(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-hydroxy-1-(phenylsulfonyl)propyl]-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-methoxytetrahydrofuran-2-yl]methyl}-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylenetetrahydrofuran-2-yl}propan-1-ol | 253128-11-9

• 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,2RS)-3-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tert-butyl(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-hydroxy-1-(phenylsulfonyl)propyl]-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-methoxytetrahydrofuran-2-yl]methyl}-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylenetetrahydrofuran-2-yl}propan-1-ol
• 英文别名: 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]-1-(benzenesulfonyl)-1-[(2S,3S,4R,5R)-5-[(2S)-2,3-bis[[tert-butyl(dimethyl)silyl]oxy]propyl]-2-[[(2R,4R,6S)-6-[2-[(2S,5S)-5-(3-hydroxypropyl)-3-methylideneoxolan-2-yl]ethyl]-4-methyl-3-methylideneoxan-2-yl]methyl]-4-methoxyoxolan-3-yl]propan-2-ol
• CAS: 253128-11-9
• 化学式: C₇₆H₁₃₉IO₁₅SSi₅
• 分子量: 1592.33
• InChiKey: WSDIAIGYXIANCQ-GGARUPNDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  18.22
• 重原子数：
  98
• 可旋转键数：
  35
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  185
• 氢给体数：
  2
• 氢受体数：
  15

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,2RS)-3-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tert-butyl(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-hydroxy-1-(phenylsulfonyl)propyl]-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-methoxytetrahydrofuran-2-yl]methyl}-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylenetetrahydrofuran-2-yl}propan-1-ol 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 以95%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-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
  参考文献：
  名称：

  Commercial Manufacture of Halaven®: Chemoselective Transformations En Route to Structurally Complex Macrocyclic Ketones

  摘要：

  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).

  DOI：

  10.1055/s-0032-1318026
• 作为产物：
  描述：

  艾瑞布林中间体 、 艾日布林中间体 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 正庚烷 为溶剂， 以95%的产率得到3-{(2S,5S)-5-[2-((2S,4R,6R)-6-{[(2S,3S,4R,5R)-3-[(1RS,2RS)-3-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tert-butyl(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-hydroxy-1-(phenylsulfonyl)propyl]-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-methoxytetrahydrofuran-2-yl]methyl}-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylenetetrahydrofuran-2-yl}propan-1-ol
  参考文献：
  名称：

  Commercial Manufacture of Halaven®: Chemoselective Transformations En Route to Structurally Complex Macrocyclic Ketones

  摘要：

  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).

  DOI：

  10.1055/s-0032-1318026