(6S)-25-hydroxy-6,19-dihydro-6,19-epidioxyvitamin D₃ | 73249-00-0

• 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: (6S)-25-hydroxy-6,19-dihydro-6,19-epidioxyvitamin D₃
• 英文别名: (7E)-(3S,6S)-6,19-epidioxy-9,10-seco-5(10),7-cholestadiene-3,25-diol；(4S,6S)-4-[(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-benzodioxin-6-ol
• CAS: 73249-00-0；96999-64-3
• 化学式: C₂₇H₄₄O₄
• 分子量: 432.644
• InChiKey: UDKXRKKPBOEFRD-XTDVUYCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 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：
  58.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6S)-25-hydroxy-6,19-dihydro-6,19-epidioxyvitamin D₃ 在 氢氧化钾 作用下， 以 氘代氯仿 、 氯仿 为溶剂， 反应 3.92h， 生成 25-hydroxy-6,19-epoxyvitamin D₃
  参考文献：
  名称：

  25-羟基维生素D3内过氧化物在人类髓样白血病细胞（HL-60）中的分化作用机理。

  摘要：

  研究了25-羟基-6,19-二氢-6,19-二氧合维生素D3 [25-（OH）D3内过氧化物2a和3a]在诱导人骨髓白血病细胞（HL-60）分化中的作用。放射性衍生物（2a'和3a'）。当HL-60细胞与标记的过氧化物（2a'和3a'）在无血清RPMI 1640培养基中孵育时，没有放射性掺入细胞的细胞溶质或染色质部分。在有或没有HL-60细胞的情况下，将放射性过氧化物（2a'）在培养基中培养3天时，大约有45％的化合物类似地转化为19,25-二羟基-6,19-二氢-6， 19-环氧维生素D3（4a）和约10％的25-羟基-6,19-环氧维生素D3（6a）。这两种新的维生素D衍生物是化学合成的，并对其生物学活性进行了测试。在诱导HL-60细胞分化中，两种化合物（4a和6a）的活性是25-（OH）D3内过氧化物（2a和3a）的活性的约2倍，是25-羟基维生素D3（1a）的活性的约7倍。这些化合

  DOI：

  10.1021/jm00147a006
• 作为产物：
  描述：

  骨化二醇 在 氧气 、 rose bengal 作用下， 以 乙醇 为溶剂， 以28%的产率得到(6R)-25-hydroxy-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

• 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.
• Mechanism of the differentiating action of 25-hydroxyvitamin D3 endoperoxides in human myeloid leukemia cells (HL-60)
  作者：Yoshiko Shiina、Chisato Miyaura、Hirofumi Tanaka、Etsuko Abe、Sachiko Yamada、Keiko Yamamoto、Eiichi Ino、Hiroaki Takayama、Isao Matsunaga

  DOI：10.1021/jm00147a006

  日期：1985.9

  The action of 25-hydroxy-6,19-dihydro-6,19-epidioxyvitamin D3 [25-(OH)D3 endoperoxides, 2a and 3a] in inducing differentiation of human myeloid leukemia cells (HL-60) was studied by using their radioactive derivatives (2a' and 3a'). When HL-60 cells were incubated with the labeled endoperoxides (2a' and 3a') in serum-free RPMI 1640 medium, no radioactivity was incorporated into either the cytosol or

  研究了25-羟基-6,19-二氢-6,19-二氧合维生素D3 [25-（OH）D3内过氧化物2a和3a]在诱导人骨髓白血病细胞（HL-60）分化中的作用。放射性衍生物（2a'和3a'）。当HL-60细胞与标记的过氧化物（2a'和3a'）在无血清RPMI 1640培养基中孵育时，没有放射性掺入细胞的细胞溶质或染色质部分。在有或没有HL-60细胞的情况下，将放射性过氧化物（2a'）在培养基中培养3天时，大约有45％的化合物类似地转化为19,25-二羟基-6,19-二氢-6， 19-环氧维生素D3（4a）和约10％的25-羟基-6,19-环氧维生素D3（6a）。这两种新的维生素D衍生物是化学合成的，并对其生物学活性进行了测试。在诱导HL-60细胞分化中，两种化合物（4a和6a）的活性是25-（OH）D3内过氧化物（2a和3a）的活性的约2倍，是25-羟基维生素D3（1a）的活性的约7倍。这些化合