butyl (22E)-(24R)-de-A,B-26,27-cyclo-24-hydroxy-8-oxo-22-cholestene-25-carboxylate | 651738-28-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: butyl (22E)-(24R)-de-A,B-26,27-cyclo-24-hydroxy-8-oxo-22-cholestene-25-carboxylate
• 英文别名: butyl 1-[(E,1R,4R)-4-[(1R,3aR,7aR)-7a-methyl-4-oxo-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-1-hydroxypent-2-enyl]cyclopropane-1-carboxylate
• CAS: 651738-28-2
• 化学式: C₂₃H₃₆O₄
• 分子量: 376.536
• InChiKey: ZNAWJIDWXHPUNF-YUUFEXMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  butyl (22E)-(24R)-de-A,B-26,27-cyclo-24-hydroxy-8-oxo-22-cholestene-25-carboxylate 在 四(三苯基膦)钯 四丁基氟化铵 、 sodium hexamethyldisilazane 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.5h， 生成 胆钙化醇杂质21(维生素D3杂质21)
  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：

  butyl (22E)-(8S)-de-A,B-8-(tert-butyldimethylsilyl)oxy-26,27-cyclo-24-oxo-22-cholestene-25-carboxylate 在 sodium tetrahydroborate 、 cerium(III) chloride 、 四丙基高钌酸铵 、 4 A molecular sieve 、 四丁基氟化铵 、 二甲基氯化铝 、 4-甲基苯磺酸吡啶 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 130.25h， 生成 butyl (22E)-(24R)-de-A,B-26,27-cyclo-24-hydroxy-8-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

文献信息

• Process for the synthesis of vitamin d compounds and intermediates for the synthesis of the compounds
  申请人：Kashiwagi Hirotaka

  公开号：US20070135394A1

  公开（公告）日：2007-06-14

  An object of the present invention is to provide a process for synthesizing a vitamin D compound by simple procedures at lower costs. The present invention provides a process for preparing a vitamin D compound and an intermediate thereof, comprising the step of: (a) mixing a ketone or aldehyde, a Wittig reagent, and a base; or (b) mixing a ketone or aldehyde and a Wittig reagent, and then adding a base to the resulting mixture.

  本发明的一个目的是提供一种通过简单程序以更低成本合成维生素D化合物的方法。本发明提供了一种制备维生素D化合物及其中间体的方法，包括以下步骤：(a)混合酮或醛、威蒂格试剂和碱；或者(b)混合酮或醛和威蒂格试剂，然后向所得混合物中加入碱。
• US9221753B2
  申请人：——

  公开号：US9221753B2

  公开（公告）日：2015-12-29
• Design and synthesis of potent vitamin D receptor antagonists with A-ring modifications: remarkable effects of 2α-methyl introduction on antagonistic activity
  作者：Toshie Fujishima、Yoshinori Kojima、Isao Azumaya、Atsushi Kittaka、Hiroaki Takayama

  DOI：10.1016/s0968-0896(03)00371-7

  日期：2003.8

  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.