methyl (2R,3S,4R,5S,7S,8Z,10S,11S,12S,13Z,16S,17R,18R,19S,20S,21Z)-5-[tert-butyl(dimethyl)silyl]oxy-19-hydroxy-7,11-bis(methoxymethoxy)-3,17-bis[(4-methoxyphenyl)methoxy]-2,4,10,12,14,16,18,20-octamethyltetracosa-8,13,21,23-tetraenoate | 216670-21-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: methyl (2R,3S,4R,5S,7S,8Z,10S,11S,12S,13Z,16S,17R,18R,19S,20S,21Z)-5-[tert-butyl(dimethyl)silyl]oxy-19-hydroxy-7,11-bis(methoxymethoxy)-3,17-bis[(4-methoxyphenyl)methoxy]-2,4,10,12,14,16,18,20-octamethyltetracosa-8,13,21,23-tetraenoate
• CAS: 216670-21-2
• 化学式: C₅₉H₉₆O₁₂Si
• 分子量: 1025.49
• InChiKey: YPMXIYAIKUEFTR-SOAUBASQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.55
• 重原子数：
  72
• 可旋转键数：
  37
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  methyl (2R,3S,4R,5S,7S,8Z,10S,11S,12S,13Z,16S,17R,18R,19S,20S,21Z)-5-[tert-butyl(dimethyl)silyl]oxy-19-hydroxy-7,11-bis(methoxymethoxy)-3,17-bis[(4-methoxyphenyl)methoxy]-2,4,10,12,14,16,18,20-octamethyltetracosa-8,13,21,23-tetraenoate 在 盐酸 、 碳酸氢钠 、 potassium carbonate 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 68.42h， 生成 盘皮海绵内酯
  参考文献：
  名称：

  Total Synthesis of (+)-Discodermolide

  摘要：

  The total synthesis of (+)-discodermolide is described. The approach involves assemblage of three key stereotriad subunits through addition of nonracemic allenyltin, -indium, and -zinc reagents to (S)-3-silyloxy-2-methylpropanal derivatives, followed by reduction of the resulting anti,syn- or syn,syn-homopropargylic alcohol adducts to the (E)-homoallylic alcohols and subsequent Sharpless epoxidation. Addition of methyl cuprate reagents of Red-Al to the resultant epoxy alcohols yielded the key precursors, alkyne 4, aldehyde 9, and alcohol 24. Addition of alkyne 4 (as the lithio species 10) to aldehyde 9 afforded the propargylic alcohol 11 as the major stereoisomer. Lindlar hydrogenation and installation of appropriate protecting groups led to aldehyde 17. This was converted to the (Z)-vinylic iodide 18 upon treatment with alpha-iodoethylidene triphenylphosphorane. Suzuki coupling of this vinylic iodide with a boranate derived from iodide 25 led to the coupled product 27 with the complete carbon backbone of (+)-discodermolide and the correct stereochemistry. The synthesis was completed by cleavage of the cyclic PMP acetal at C1 with i-Bu2AlH and three-step oxidation-esterification to the ester 31. Cleavage of the C19 Et3Si ether and C19 carbamate formation followed by cleavage of the remaining alcohol protecting groups, first with DDQ and then aqueous HCl, afforded (+)-discodermolide (36).

  DOI：

  10.1021/jo9811423
• 作为产物：
  描述：

  Benzoic acid (1S,4S,5S,6S)-1-{(2S,3R)-2-(tert-butyl-dimethyl-silanyloxy)-3-[(2R,4R,5S)-2-(4-methoxy-phenyl)-5-methyl-[1,3]dioxan-4-yl]-butyl}-5-methoxymethoxy-4,6-dimethyl-7-triethylsilanyloxy-hept-2-ynyl ester 在 Lindlar's catalyst (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium chlorite 、 potassium phosphate 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 氢气 、 叔丁基锂 、 四丁基碘化铵 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 、 对甲苯磺酸 、 氟化氢吡啶 、 N,N-二异丙基乙胺 、 8-甲氧基-9-硼杂双环[3.3.1]壬烷 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 正己烷 、 二氯甲烷 、 叔丁醇 、 苯 为溶剂， 反应 89.88h， 生成 methyl (2R,3S,4R,5S,7S,8Z,10S,11S,12S,13Z,16S,17R,18R,19S,20S,21Z)-5-[tert-butyl(dimethyl)silyl]oxy-19-hydroxy-7,11-bis(methoxymethoxy)-3,17-bis[(4-methoxyphenyl)methoxy]-2,4,10,12,14,16,18,20-octamethyltetracosa-8,13,21,23-tetraenoate
  参考文献：
  名称：

  Total Synthesis of (+)-Discodermolide

  摘要：

  The total synthesis of (+)-discodermolide is described. The approach involves assemblage of three key stereotriad subunits through addition of nonracemic allenyltin, -indium, and -zinc reagents to (S)-3-silyloxy-2-methylpropanal derivatives, followed by reduction of the resulting anti,syn- or syn,syn-homopropargylic alcohol adducts to the (E)-homoallylic alcohols and subsequent Sharpless epoxidation. Addition of methyl cuprate reagents of Red-Al to the resultant epoxy alcohols yielded the key precursors, alkyne 4, aldehyde 9, and alcohol 24. Addition of alkyne 4 (as the lithio species 10) to aldehyde 9 afforded the propargylic alcohol 11 as the major stereoisomer. Lindlar hydrogenation and installation of appropriate protecting groups led to aldehyde 17. This was converted to the (Z)-vinylic iodide 18 upon treatment with alpha-iodoethylidene triphenylphosphorane. Suzuki coupling of this vinylic iodide with a boranate derived from iodide 25 led to the coupled product 27 with the complete carbon backbone of (+)-discodermolide and the correct stereochemistry. The synthesis was completed by cleavage of the cyclic PMP acetal at C1 with i-Bu2AlH and three-step oxidation-esterification to the ester 31. Cleavage of the C19 Et3Si ether and C19 carbamate formation followed by cleavage of the remaining alcohol protecting groups, first with DDQ and then aqueous HCl, afforded (+)-discodermolide (36).

  DOI：

  10.1021/jo9811423

文献信息

• Total Synthesis of (+)-Discodermolide
  作者：James A. Marshall、Brian A. Johns

  DOI：10.1021/jo9811423

  日期：1998.10.1

  The total synthesis of (+)-discodermolide is described. The approach involves assemblage of three key stereotriad subunits through addition of nonracemic allenyltin, -indium, and -zinc reagents to (S)-3-silyloxy-2-methylpropanal derivatives, followed by reduction of the resulting anti,syn- or syn,syn-homopropargylic alcohol adducts to the (E)-homoallylic alcohols and subsequent Sharpless epoxidation. Addition of methyl cuprate reagents of Red-Al to the resultant epoxy alcohols yielded the key precursors, alkyne 4, aldehyde 9, and alcohol 24. Addition of alkyne 4 (as the lithio species 10) to aldehyde 9 afforded the propargylic alcohol 11 as the major stereoisomer. Lindlar hydrogenation and installation of appropriate protecting groups led to aldehyde 17. This was converted to the (Z)-vinylic iodide 18 upon treatment with alpha-iodoethylidene triphenylphosphorane. Suzuki coupling of this vinylic iodide with a boranate derived from iodide 25 led to the coupled product 27 with the complete carbon backbone of (+)-discodermolide and the correct stereochemistry. The synthesis was completed by cleavage of the cyclic PMP acetal at C1 with i-Bu2AlH and three-step oxidation-esterification to the ester 31. Cleavage of the C19 Et3Si ether and C19 carbamate formation followed by cleavage of the remaining alcohol protecting groups, first with DDQ and then aqueous HCl, afforded (+)-discodermolide (36).