(23R,24R)-25-dehydro-1α-hydroxy-24-methylvitamin D₃-26,23-lactone

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (23R,24R)-25-dehydro-1α-hydroxy-24-methylvitamin D₃-26,23-lactone
• 英文别名: 20(R)-(tetrahydro-3-methylene-2-furanone-4-methyl-5-yl)methyl-9,10-secopregna-5(Z),7(E),10(19)-triene-1α,3β-diol；(4R,5R)-5-[(2R)-2-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(3S,5R)-3,5-dihydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]propyl]-4-methyl-3-methylideneoxolan-2-one
• 化学式: C₂₈H₄₀O₄
• 分子量: 440.623
• InChiKey: RBARJWNZIPXVBN-MPWBFETKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S)-2-[(1R,3aR,7aR)-octahydro-7a-methyl-4-oxo-4H-inden-1-yl]propyl 4-methylbenzenesulfonate 在 四(三苯基膦)钯 chromium chloride 、 lithium aluminium tetrahydride 、 sodium hexamethyldisilazane 、 二异丁基氢化铝 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 9.25h， 生成 (23R,24R)-25-dehydro-1α-hydroxy-24-methylvitamin D₃-26,23-lactone
  参考文献：
  名称：

  Dramatic Enhancement of Antagonistic Activity on Vitamin D Receptor:  A Double Functionalization of 1α-Hydroxyvitamin D₃ 26,23-Lactones

  摘要：

  [GRAPHICS]The synthesis of novel vitamin D receptor antagonists, 24-methyl-1alpha-hydroxyvitamin D-3 26,23-lactones, is reported. We found that the biological activities of the vitamin D-3 lactones were affected by the structure of the lactone part. Furthermore, introduction of a 2alpha-methyl group into the 24-methylvitamin D-3 lactones dramatically enhanced their anti-vitamin D activity.

  DOI：

  10.1021/ol035922w

文献信息

• Further Synthetic and Biological Studies on Vitamin D Hormone Antagonists Based on C24-Alkylation and C2α-Functionalization of 25-Dehydro-1α-hydroxyvitamin D₃-26,23-lactones
  作者：Nozomi Saito、Toshihiro Matsunaga、Hiroshi Saito、Miyuki Anzai、Kazuya Takenouchi、Daishiro Miura、Jun-ichi Namekawa、Seiichi Ishizuka、Atsushi Kittaka

  DOI：10.1021/jm060797q

  日期：2006.11.30

  on process, and the 23,24-trans lactone derivatives were derived from these via inversion of the C23 stereochemistry. The biological evaluation revealed that both binding affinity for chick vitamin D hormone receptor and antagonistic activity (inhibition of vitamin D hormone induced HL-60 cell differentiation) were affected by the orientation and chain-length of the primary alkyl group on the lactone

  高效合成和生物学评估80种新型25-脱氢-1α-羟基维生素D3-26,23S-内酯2（TEI-9647）及其23R差向异构体（3），其中内酯环通过引入描述了在C24位的C1至C4伯烷基（5组4个非对映异构体），以及它们的C2α-甲基，3-羟丙基和3-羟基丙氧基取代的衍生物。维生素D3的三烯结构是通过A环前体烯炔的钯催化烯基环化和侧链上具有C24烷基化内酯部分的CD环对应的溴烯烃而构建的。具有23,24-顺式内酯的CD环前体是通过使用铬介导的顺-选择性烯丙基化-内酯化工艺制备的，然后将23,24-顺式内酯 通过反式的C23立体化学从中衍生出24反式内酯衍生物。生物学评估表明，对鸡维生素D激素受体的结合亲和力和拮抗活性（抑制维生素D激素诱导的HL-60细胞分化）均受内酯环上伯烷基的取向和链长的影响。此外，C24烷基化的维生素D3内酯的C2alpha官能化大大增强了它们的生物学活性。最有效的化合
• VITAMIN D3 LACTONE DERIVATIVE
  申请人：Teijin Pharma Limited

  公开号：EP1589009B1

  公开（公告）日：2014-10-08
• Dramatic Enhancement of Antagonistic Activity on Vitamin D Receptor:  A Double Functionalization of 1α-Hydroxyvitamin D₃ 26,23-Lactones
  作者：Nozomi Saito、Hiroshi Saito、Miyuki Anzai、Akihiro Yoshida、Toshie Fujishima、Kazuya Takenouchi、Daishiro Miura、Seiichi Ishizuka、Hiroaki Takayama、Atsushi Kittaka

  DOI：10.1021/ol035922w

  日期：2003.12.1

  [GRAPHICS]The synthesis of novel vitamin D receptor antagonists, 24-methyl-1alpha-hydroxyvitamin D-3 26,23-lactones, is reported. We found that the biological activities of the vitamin D-3 lactones were affected by the structure of the lactone part. Furthermore, introduction of a 2alpha-methyl group into the 24-methylvitamin D-3 lactones dramatically enhanced their anti-vitamin D activity.