(R)-5-{(R)-2-[(1R,4E,3aR,7aR)-4-bromomethylene-7a-methylperhydroinden-1-yl]propyl}-4,4-dimethyl-3-methylenedihydrofuran-2-one | 737783-31-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (R)-5-{(R)-2-[(1R,4E,3aR,7aR)-4-bromomethylene-7a-methylperhydroinden-1-yl]propyl}-4,4-dimethyl-3-methylenedihydrofuran-2-one
• 英文别名: (5R)-5-[(2R)-2-[(1R,3aR,4E,7aR)-4-(bromomethylidene)-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]propyl]-4,4-dimethyl-3-methylideneoxolan-2-one
• CAS: 737783-31-2
• 化学式: C₂₁H₃₁BrO₂
• 分子量: 395.38
• InChiKey: OWSTXHJJZJQPSY-ALGOAALVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-5-{(R)-2-[(1R,4E,3aR,7aR)-4-bromomethylene-7a-methylperhydroinden-1-yl]propyl}-4,4-dimethyl-3-methylenedihydrofuran-2-one 在 四(三苯基膦)钯 氢氟酸 、 三乙胺 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 3.0h， 生成 (23R)-25-dehydro-1α-hydroxy-2α-(3-hydroxypropoxy)-24,24-dimethyl-vitamin D₃-26,23-lactone
  参考文献：
  名称：

  24,24-Dimethylvitamin D3-26,23-lactones and their 2α-functionalized analogues as highly potent VDR antagonists

  摘要：

  Novel vitamin D receptor (VDR) antagonists, 24,24-dimethyl-1alpha-hydroxyvitamin D-3-26,23-lactones (8 and 9) and their C2alpha functionalized analogues (8a-c and 9a-c) were efficiently synthesized and their biological activities were evaluated. The construction of vitamin D-3 triene skeleton was achieved by palladium-catalyzed alkenylative cyclization of A-ring precursor enyne (22 and 22a-c) with CD-ring bromoolefin having a 24,24-dimethyl-alpha-methylene-gamma-lactone unit on the side chain (13 and 14). The CD-ring precursors 13 and 14 were prepared by using chromium-mediated allylation of the aldehyde 10 derived from vitamin D-2. On the other hand, the A-ring enyne having 2alpha-(3-hydroxypropyl) group (22b) was newly synthesized from epoxide 15 using regio- and stereoselective alkylation methodology. The potency of the antagonistic activity of the newly designed analogues (8 and 9) increased up to 12 times that of TEI-9647 (2). Furthermore, introduction of the three motifs, that is, a methyl (8a and 9a), an omega-hydroxypropyl (8b and 9b) or an omega-hydroxypropoxyl group (8c and 9c) into the C2alpha position of 8 and 9, respectively, resulted in remarkable enhancement, up to 89 times, of the antagonistic activity on VDR. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.05.113
• 作为产物：
  描述：

  methyl 3-hydroxy-3-methyl-2-methylenebutanoate 在 chromium chloride 、 lithium aluminium tetrahydride 、 三溴化磷 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 2.0h， 生成 (R)-5-{(R)-2-[(1R,4E,3aR,7aR)-4-bromomethylene-7a-methylperhydroinden-1-yl]propyl}-4,4-dimethyl-3-methylenedihydrofuran-2-one
  参考文献：
  名称：

  24,24-Dimethylvitamin D3-26,23-lactones and their 2α-functionalized analogues as highly potent VDR antagonists

  摘要：

  Novel vitamin D receptor (VDR) antagonists, 24,24-dimethyl-1alpha-hydroxyvitamin D-3-26,23-lactones (8 and 9) and their C2alpha functionalized analogues (8a-c and 9a-c) were efficiently synthesized and their biological activities were evaluated. The construction of vitamin D-3 triene skeleton was achieved by palladium-catalyzed alkenylative cyclization of A-ring precursor enyne (22 and 22a-c) with CD-ring bromoolefin having a 24,24-dimethyl-alpha-methylene-gamma-lactone unit on the side chain (13 and 14). The CD-ring precursors 13 and 14 were prepared by using chromium-mediated allylation of the aldehyde 10 derived from vitamin D-2. On the other hand, the A-ring enyne having 2alpha-(3-hydroxypropyl) group (22b) was newly synthesized from epoxide 15 using regio- and stereoselective alkylation methodology. The potency of the antagonistic activity of the newly designed analogues (8 and 9) increased up to 12 times that of TEI-9647 (2). Furthermore, introduction of the three motifs, that is, a methyl (8a and 9a), an omega-hydroxypropyl (8b and 9b) or an omega-hydroxypropoxyl group (8c and 9c) into the C2alpha position of 8 and 9, respectively, resulted in remarkable enhancement, up to 89 times, of the antagonistic activity on VDR. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.05.113

文献信息

• VITAMIN D3 LACTONE DERIVATIVE
  申请人：Teijin Pharma Limited

  公开号：EP1589009B1

  公开（公告）日：2014-10-08
• US9073885B2
  申请人：——

  公开号：US9073885B2

  公开（公告）日：2015-07-07
• 24,24-Dimethylvitamin D3-26,23-lactones and their 2α-functionalized analogues as highly potent VDR antagonists
  作者：Nozomi Saito、Manami Masuda、Toshihiro Matsunaga、Hiroshi Saito、Miyuki Anzai、Kazuya Takenouchi、Daishiro Miura、Seiichi Ishizuka、Midori Takimoto-Kamimura、Atsushi Kittaka

  DOI：10.1016/j.tet.2004.05.113

  日期：2004.8

  Novel vitamin D receptor (VDR) antagonists, 24,24-dimethyl-1alpha-hydroxyvitamin D-3-26,23-lactones (8 and 9) and their C2alpha functionalized analogues (8a-c and 9a-c) were efficiently synthesized and their biological activities were evaluated. The construction of vitamin D-3 triene skeleton was achieved by palladium-catalyzed alkenylative cyclization of A-ring precursor enyne (22 and 22a-c) with CD-ring bromoolefin having a 24,24-dimethyl-alpha-methylene-gamma-lactone unit on the side chain (13 and 14). The CD-ring precursors 13 and 14 were prepared by using chromium-mediated allylation of the aldehyde 10 derived from vitamin D-2. On the other hand, the A-ring enyne having 2alpha-(3-hydroxypropyl) group (22b) was newly synthesized from epoxide 15 using regio- and stereoselective alkylation methodology. The potency of the antagonistic activity of the newly designed analogues (8 and 9) increased up to 12 times that of TEI-9647 (2). Furthermore, introduction of the three motifs, that is, a methyl (8a and 9a), an omega-hydroxypropyl (8b and 9b) or an omega-hydroxypropoxyl group (8c and 9c) into the C2alpha position of 8 and 9, respectively, resulted in remarkable enhancement, up to 89 times, of the antagonistic activity on VDR. (C) 2004 Elsevier Ltd. All rights reserved.