butyl (22E)-(8S)-de-A,B-8-(tert-butyldimethylsilyl)oxy-26,27-cyclo-24-oxo-22-cholestene-25-carboxylate | 651738-11-3

• 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: butyl (22E)-(8S)-de-A,B-8-(tert-butyldimethylsilyl)oxy-26,27-cyclo-24-oxo-22-cholestene-25-carboxylate
• CAS: 651738-11-3
• 化学式: C₂₉H₅₀O₄Si
• 分子量: 490.799
• InChiKey: LZSNBWPHEPQSKH-FGMWMLCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.48
• 重原子数：
  34.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  butyl (22E)-(8S)-de-A,B-8-(tert-butyldimethylsilyl)oxy-26,27-cyclo-24-oxo-22-cholestene-25-carboxylate 在 四(三苯基膦)钯 sodium tetrahydroborate 、 cerium(III) chloride 、 四丙基高钌酸铵 、 4 A molecular sieve 、 四丁基氟化铵 、 sodium hexamethyldisilazane 、 二甲基氯化铝 、 4-甲基苯磺酸吡啶 、 N-甲基吗啉氧化物 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 133.75h， 生成 24-epi-3,5-Bis(O-tert-butyldimethylsilyl) ZK 159222
  参考文献：
  名称：

  Design and synthesis of potent vitamin D receptor antagonists with A-ring modifications: remarkable effects of 2α-methyl introduction on antagonistic activity

  摘要：

  Novel A-ring analogues of the vitamin D receptor (VDR) antagonist (3a), ZK-159222, and its 24-epimer (3b) were convergently synthesized. Preparation of the CD-ring portions with the side chains of 3a,b, followed by palladium-catalyzed cross-coupling with the A-ring enyne precursors (15a,b), (3S,4S,5R)- and (3S,4S,5S)-bis[(tert-butyldimethylsilyl)oxy]-4-methyloct-1-en-7-yne, afforded the 2alpha-methyl-introduced analogues (4a,b) and their 3-epimers (5a,b). The biological profiles of the hybrid analogues were assessed in terms of affinity for VDR, and antagonistic activity to inhibit HL-60 cell differentiation induced by the natural hormone, 1alpha,25-dihydroxyvitamin D-3. The analogue 4a showed an approximately fivefold higher antagonistic activity compared with 3a. The 2alpha-methyl introduction into 3a increased the receptor affinity, thereby enhancing VDR antagonism. This approach to design potent antagonists based on hybridization of structural motifs in the A-ring and in the side chain may prove to be valuable. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00371-7
• 作为产物：
  描述：

  甲基1-乙酰基环丙烷羧酸酯 、 (S)-2-[(1R,3aR,4S,7aR)-octahydro-4-[(1,1-dimethylethyl)dimethylsilyloxy]-7a-methyl-1H-inden-1-yl]propanal 、 正丁醇 以61%的产率得到butyl (22E)-(8S)-de-A,B-8-(tert-butyldimethylsilyl)oxy-26,27-cyclo-24-oxo-22-cholestene-25-carboxylate
  参考文献：
  名称：

  Design and synthesis of potent vitamin D receptor antagonists with A-ring modifications: remarkable effects of 2α-methyl introduction on antagonistic activity

  摘要：

  Novel A-ring analogues of the vitamin D receptor (VDR) antagonist (3a), ZK-159222, and its 24-epimer (3b) were convergently synthesized. Preparation of the CD-ring portions with the side chains of 3a,b, followed by palladium-catalyzed cross-coupling with the A-ring enyne precursors (15a,b), (3S,4S,5R)- and (3S,4S,5S)-bis[(tert-butyldimethylsilyl)oxy]-4-methyloct-1-en-7-yne, afforded the 2alpha-methyl-introduced analogues (4a,b) and their 3-epimers (5a,b). The biological profiles of the hybrid analogues were assessed in terms of affinity for VDR, and antagonistic activity to inhibit HL-60 cell differentiation induced by the natural hormone, 1alpha,25-dihydroxyvitamin D-3. The analogue 4a showed an approximately fivefold higher antagonistic activity compared with 3a. The 2alpha-methyl introduction into 3a increased the receptor affinity, thereby enhancing VDR antagonism. This approach to design potent antagonists based on hybridization of structural motifs in the A-ring and in the side chain may prove to be valuable. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00371-7