1α,25-dihydroxy-6,19-dihydro-6,19-epidioxyvitamin D₃

• 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: 1α,25-dihydroxy-6,19-dihydro-6,19-epidioxyvitamin D₃
• 英文别名: (6R)-6,19-epidioxy-1alpha,25-dihydroxy-6,19-dihydrovitamin D3/(6R)-6,19-epidioxy-1alpha,25-dihydroxy-6,19-dihydrocholecalciferol；(5S,7R)-1-[(E)-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]methyl]-1,4,5,6,7,8-hexahydro-2,3-benzodioxine-5,7-diol
• 化学式: C₂₇H₄₄O₅
• 分子量: 448.643
• InChiKey: JIYDMMUJCNTFKM-SRQHBZITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  79.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  骨化三醇 在 氧气 、 rose bengal 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 1α,25-dihydroxy-6,19-dihydro-6,19-epidioxyvitamin D₃
  参考文献：
  名称：

  Syntheses and differentiating action of vitamin D endoperoxides. Singlet oxygen adducts of vitamin D derivatives in human myeloid leukemia cells (HL-60)

  摘要：

  Singlet oxygen adducts of various vitamin D derivatives, 6,19-dihydro-6,19-epidioxyvitamin D (vitamin D endoperoxides, 2 and 2'), were chemically synthesized, and their biological activity in inducing differentiation of a human myeloid leukemia cell line (HL-60 cells) was examined. The potency of the endoperoxides derived from vitamin D derivatives possessing the 1 alpha-hydroxyl group such as 1 alpha, 25-dihydroxyvitamin D3 endoperoxides (2b and 2b') was markedly (10(-2)) diminished relative to the respective parent vitamin D compounds. In contrast, 25-hydroxyvitamin D3 endoperoxides [25-(OH)D3 endoperoxides, 2a and 2a'] and their analogues fluorinated at the 24- or 26- and 27-positions were 2.5-10 times more potent than 25-hydroxyvitamin D3 (1a) in spite of the absence of the conjugated triene structure typical of vitamin D compounds. The potency of these vitamin D endoperoxides (2 and 2'), especially those lacking the 1 alpha-hydroxyl group, in inducing differentiation of HL-60 cells was not correlated with their activity in binding to the cytosol receptor for 1 alpha, 25-dihydroxyvitamin D3 (1b). The binding efficiency to the receptor was relatively lower than the differentiating activity. To examine the action of vitamin D endoperoxides, carbon analogues of 25-(OH)D3 endoperoxides, two C-6 epimers of 25-hydroxy-6,19-dihydro-6,19-ethanovitamin D3 (6 and 6'), were synthesized. The carbon analogues (6 and 6') had no potential to induce differentiation of HL-60 cells. These results suggest that vitamin D endoperoxides (2 and 2') express their biological activity probably after being converted to some other compounds.

  DOI：

  10.1021/jm00147a005

文献信息

• Novel vitamin D3 derivatives and process for producing the same
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP0081793A1

  公开（公告）日：1983-06-22

  There are disclosed 6,19-epidioxyvitamin D3 derivatives which are represented by the formula wherein R1, R2 and R3 are each a hydrogen atom or a hydroxyl group; when R1 is a hydrogen atom, R2 represents a hydroxyl group and R3 is a hydrogen atom or a hydroxyl group; when both R1 and R2 represent a hydroxyl group, R3 is a hydrogen atom or a hydroxyl group; and when R1 is a hydroxyl group and R2 is a hydrogen atom, R3 represents a hydroxyl group. The compounds are highly capable of inducing differentiation of human myeloid leukemia cells with minimum effects on calcium metabolism and are useful as an agent to treat leukemia.

  已公开的 6,19-epidioxyvitamin D3 衍生物由式表示，其中 R1、R2 和 R3 各为氢原子或羟基；当 R1 为氢原子时，R2 代表羟基，R3 为氢原子或羟基；当 R1 和 R2 均代表羟基时，R3 为氢原子或羟基；当 R1 为羟基，R2 为氢原子时，R3 代表羟基。 这些化合物具有很强的诱导人类髓性白血病细胞分化的能力，对钙代谢的影响最小，可用作治疗白血病的药物。
• US4517125A
  申请人：——

  公开号：US4517125A

  公开（公告）日：1985-05-14
• Syntheses and differentiating action of vitamin D endoperoxides. Singlet oxygen adducts of vitamin D derivatives in human myeloid leukemia cells (HL-60)
  作者：Sachiko Yamada、Keiko Yamamoto、Hiroyuki Naito、Takayoshi Suzuki、Masayuki Ohmori、Hiroaki Takayama、Yoshiko Shiina、Chisato Miyaura、Hirofumi Tanaka

  DOI：10.1021/jm00147a005

  日期：1985.9

  Singlet oxygen adducts of various vitamin D derivatives, 6,19-dihydro-6,19-epidioxyvitamin D (vitamin D endoperoxides, 2 and 2'), were chemically synthesized, and their biological activity in inducing differentiation of a human myeloid leukemia cell line (HL-60 cells) was examined. The potency of the endoperoxides derived from vitamin D derivatives possessing the 1 alpha-hydroxyl group such as 1 alpha, 25-dihydroxyvitamin D3 endoperoxides (2b and 2b') was markedly (10(-2)) diminished relative to the respective parent vitamin D compounds. In contrast, 25-hydroxyvitamin D3 endoperoxides [25-(OH)D3 endoperoxides, 2a and 2a'] and their analogues fluorinated at the 24- or 26- and 27-positions were 2.5-10 times more potent than 25-hydroxyvitamin D3 (1a) in spite of the absence of the conjugated triene structure typical of vitamin D compounds. The potency of these vitamin D endoperoxides (2 and 2'), especially those lacking the 1 alpha-hydroxyl group, in inducing differentiation of HL-60 cells was not correlated with their activity in binding to the cytosol receptor for 1 alpha, 25-dihydroxyvitamin D3 (1b). The binding efficiency to the receptor was relatively lower than the differentiating activity. To examine the action of vitamin D endoperoxides, carbon analogues of 25-(OH)D3 endoperoxides, two C-6 epimers of 25-hydroxy-6,19-dihydro-6,19-ethanovitamin D3 (6 and 6'), were synthesized. The carbon analogues (6 and 6') had no potential to induce differentiation of HL-60 cells. These results suggest that vitamin D endoperoxides (2 and 2') express their biological activity probably after being converted to some other compounds.