tert-butyl-[(1R,2R,3R,5Z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-2-(3-fluoropropyl)-4-methylidenecyclohexyl]oxy-dimethylsilane | 166819-31-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl-[(1R,2R,3R,5Z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-2-(3-fluoropropyl)-4-methylidenecyclohexyl]oxy-dimethylsilane
• CAS: 166819-31-4
• 化学式: C₃₆H₅₆FO₃PSi₂
• 分子量: 642.982
• InChiKey: YUYPUTLOOYDLNL-DOGHXCKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.03
• 重原子数：
  43
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl-[(1R,2R,3R,5Z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-2-(3-fluoropropyl)-4-methylidenecyclohexyl]oxy-dimethylsilane 在 4 A molecular sieve 、 四丁基氟化铵 、 苯基锂 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 2.63h， 生成 2β-(3'-Fluoropropyl)-1β,25-dihydroxyvitamin D3
  参考文献：
  名称：

  2-Fluoroalkyl A-Ring Analogs of 1,25-Dihydroxyvitamin D3. Stereocontrolled Total Synthesis via Intramolecular and Intermolecular Diels-Alder Cycloadditions. Preliminary Biological Testing

  摘要：

  Intramolecular Diels-Alder (IMDA) cycloadditions of electron-rich trans-vinylic silaketal groups tethered via a chiral, nonracemic 1,3-butanediol auxiliary to electron-poor 2-pyrone-3-carboxylates (e.g. (R)-9, (S)-14) were promoted by zinc dibromide and proceeded unexpectedly in a stepwise, ionic fashion to form exclusively cis-4,5-disubstituted bicyclic lactones 10 and 15 with nearly complete asymmetric induction. Confirmation of the stereochemical outcome of these nonconcerted IMDA cycloadditions was achieved by H-1 NMR spectroscopy and by X-ray crystallography. Fluorinated bicycloadduct (-)-15a was converted smoothly in 13 steps into the lipophilic calcitriol analog 2 beta-(3'-flubropropyl)-1 beta,25-dihydroxyvitam D-3 ((-)-5). Intermolecular, concerted, 11 kbar, inverse-electron-demand 4 + 2-cycloaddition of bis-silylated Z-enol ether 22c, carrying two different silyl groups, with commercial methyl 2-pyrone-3-carboxylate gave in gram amounts only vicinally cis-disubstituted bicycloadduct (+/-)-23c. Chemospecific monodesilylation using sodium azide and then fluorination using Et(2)NSF(3) (DAST) gave fluoroalkyl bicyclic lactone (+/-)-25. This bicyclic lactone (+/-)-25 was transformed into fluorinated, racemic, A-ring phosphine oxide (+/-)-30 that was coupled with enantiomerically pure C,D-ring ketone (+)-21 to form enantiomerically pure diastereomers (-)-4 and (+)-4' as fluorinated, lipophilic, A-ring analogs of 1,25-dihydroxyvitamin D-3(calcitriol). Preliminary biological testing (Table I) showed that only those diastereomers having the unnatural 1 beta-hydroxyl group stereochemistry (i.e. (+)-3', (+)-4', and (-)-5) had relatively high affinities for the calf thymus vitamin D receptor and significant antiproliferative and differentiation-inducing potencies in HL-60 cells.

  DOI：

  10.1021/jo00119a045
• 作为产物：
  描述：

  tert-butyl-[(1R,2R,3R,5Z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-chloroethylidene)-2-(3-fluoropropyl)-4-methylidenecyclohexyl]oxy-dimethylsilane 在 双氧水 作用下， 以 四氢呋喃 为溶剂， 反应 2.33h， 生成 tert-butyl-[(1R,2R,3R,5Z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-2-(3-fluoropropyl)-4-methylidenecyclohexyl]oxy-dimethylsilane
  参考文献：
  名称：

  2-Fluoroalkyl A-Ring Analogs of 1,25-Dihydroxyvitamin D3. Stereocontrolled Total Synthesis via Intramolecular and Intermolecular Diels-Alder Cycloadditions. Preliminary Biological Testing

  摘要：

  Intramolecular Diels-Alder (IMDA) cycloadditions of electron-rich trans-vinylic silaketal groups tethered via a chiral, nonracemic 1,3-butanediol auxiliary to electron-poor 2-pyrone-3-carboxylates (e.g. (R)-9, (S)-14) were promoted by zinc dibromide and proceeded unexpectedly in a stepwise, ionic fashion to form exclusively cis-4,5-disubstituted bicyclic lactones 10 and 15 with nearly complete asymmetric induction. Confirmation of the stereochemical outcome of these nonconcerted IMDA cycloadditions was achieved by H-1 NMR spectroscopy and by X-ray crystallography. Fluorinated bicycloadduct (-)-15a was converted smoothly in 13 steps into the lipophilic calcitriol analog 2 beta-(3'-flubropropyl)-1 beta,25-dihydroxyvitam D-3 ((-)-5). Intermolecular, concerted, 11 kbar, inverse-electron-demand 4 + 2-cycloaddition of bis-silylated Z-enol ether 22c, carrying two different silyl groups, with commercial methyl 2-pyrone-3-carboxylate gave in gram amounts only vicinally cis-disubstituted bicycloadduct (+/-)-23c. Chemospecific monodesilylation using sodium azide and then fluorination using Et(2)NSF(3) (DAST) gave fluoroalkyl bicyclic lactone (+/-)-25. This bicyclic lactone (+/-)-25 was transformed into fluorinated, racemic, A-ring phosphine oxide (+/-)-30 that was coupled with enantiomerically pure C,D-ring ketone (+)-21 to form enantiomerically pure diastereomers (-)-4 and (+)-4' as fluorinated, lipophilic, A-ring analogs of 1,25-dihydroxyvitamin D-3(calcitriol). Preliminary biological testing (Table I) showed that only those diastereomers having the unnatural 1 beta-hydroxyl group stereochemistry (i.e. (+)-3', (+)-4', and (-)-5) had relatively high affinities for the calf thymus vitamin D receptor and significant antiproliferative and differentiation-inducing potencies in HL-60 cells.

  DOI：

  10.1021/jo00119a045

文献信息

• 2-Fluoroalkyl A-Ring Analogs of 1,25-Dihydroxyvitamin D3. Stereocontrolled Total Synthesis via Intramolecular and Intermolecular Diels-Alder Cycloadditions. Preliminary Biological Testing
  作者：Gary H. Posner、Cheon-Gyu Cho、Tizah E. N. Anjeh、Neil Johnson、Ronald L. Horst、Tadashi Kobayashi、Toshio Okano、Naoko Tsugawa

  DOI：10.1021/jo00119a045

  日期：1995.7

  Intramolecular Diels-Alder (IMDA) cycloadditions of electron-rich trans-vinylic silaketal groups tethered via a chiral, nonracemic 1,3-butanediol auxiliary to electron-poor 2-pyrone-3-carboxylates (e.g. (R)-9, (S)-14) were promoted by zinc dibromide and proceeded unexpectedly in a stepwise, ionic fashion to form exclusively cis-4,5-disubstituted bicyclic lactones 10 and 15 with nearly complete asymmetric induction. Confirmation of the stereochemical outcome of these nonconcerted IMDA cycloadditions was achieved by H-1 NMR spectroscopy and by X-ray crystallography. Fluorinated bicycloadduct (-)-15a was converted smoothly in 13 steps into the lipophilic calcitriol analog 2 beta-(3'-flubropropyl)-1 beta,25-dihydroxyvitam D-3 ((-)-5). Intermolecular, concerted, 11 kbar, inverse-electron-demand 4 + 2-cycloaddition of bis-silylated Z-enol ether 22c, carrying two different silyl groups, with commercial methyl 2-pyrone-3-carboxylate gave in gram amounts only vicinally cis-disubstituted bicycloadduct (+/-)-23c. Chemospecific monodesilylation using sodium azide and then fluorination using Et(2)NSF(3) (DAST) gave fluoroalkyl bicyclic lactone (+/-)-25. This bicyclic lactone (+/-)-25 was transformed into fluorinated, racemic, A-ring phosphine oxide (+/-)-30 that was coupled with enantiomerically pure C,D-ring ketone (+)-21 to form enantiomerically pure diastereomers (-)-4 and (+)-4' as fluorinated, lipophilic, A-ring analogs of 1,25-dihydroxyvitamin D-3(calcitriol). Preliminary biological testing (Table I) showed that only those diastereomers having the unnatural 1 beta-hydroxyl group stereochemistry (i.e. (+)-3', (+)-4', and (-)-5) had relatively high affinities for the calf thymus vitamin D receptor and significant antiproliferative and differentiation-inducing potencies in HL-60 cells.