De-A,B-24-oxo-25-hydroxy-cholestan-8-benzyloxymethyl ether | 271796-45-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: De-A,B-24-oxo-25-hydroxy-cholestan-8-benzyloxymethyl ether
• CAS: 271796-45-3
• 化学式: C₂₆H₄₀O₄
• 分子量: 416.601
• InChiKey: MDSKUKWDIWUNDP-FXCZLNNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.52
• 重原子数：
  30.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  55.76
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  De-A,B-24-oxo-25-hydroxy-cholestan-8-benzyloxymethyl ether 在 palladium on activated charcoal 氢气 、 4-甲基苯磺酸吡啶 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 55.58h， 生成 De-A,B-24-oxo-23,25-(isopropylidenedioxy)cholestan-8-ol
  参考文献：
  名称：

  Synthesis and biological activities of the two C(23) epimers of 1α,23,25-trihydroxy-24-oxo-19-nor-vitamin D3: novel analogs of 1α,23(S),25-trihydroxy-24-oxo-vitamin D3, a natural metabolite of 1α,25-dihydroxyvitamin D3

  摘要：

  In a previous report. we indicated that 1 alpha,23(S).25-trihydroxy-23-oxovitamin D-3 [1 alpha,23(S).25(OH)(3)-24-oxo-D-3], a natural metabolite of 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] is almost equipotent to 1 alpha,25(OH)(2)D-3 in suppressing parathyroid hormone (PTH) secretion (Lee et al., 1997. Biochemistry 36, 9429-9437). Also, 1 alpha,23(S),25(OH)(3)-24-oxo-D-3 has been shown to possess only weak in vivo calcemic actions. Thus. vitamin D-3 analogs structurally related to 1 alpha,23(S),25(OH)(3)-24-oxo-D-3 may have therapeutic value. Furthermore. biologic activity studies of various synthetic analogs of 1 alpha,25(OH)(2)D-3 showed that the removal of carbon-19 (C-19) reduces the calcemic activity of 1 alpha,25(OH)(2)D-3. Therefore, in an attempt to produce vitamin D-3 analogs with a better therapeutic index, we synthesized C(23) epimers of 1 alpha,23,25(OH)(3)-24-oxo-19-nor-vitamin D-3 1 alpha,23,25(OH)(3)-24-oxo-19-nor-D-3]. The two epimers were compared to 1 alpha,25(OH)(2)-19-nor-D-3 and 1 alpha.25(OH)(2)D-3 in their ability to generate biologic activities in several in vitro assay systems. In the assay measuring the suppression of parathyroid hormone (PTH) secretion in bovine parathyroid cells, 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 was as potent as 1 alpha,25(OH)(2)-19-nor-D-3 but was less potent than 1 alpha,25(OH)(2)D-3. In the same assay 1 alpha,23(R)25(OH)(3)-24-oxo-19-nor-D-3 exhibited greater potency than 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3. In the assays measuring the ability of vitamin D compounds to inhibit clonal growth and to induce differentiation of human promyelocytic leukemia (HL60) cells, 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 was less potent than 1 alpha,25(OH)(2)-19-nor-D-3 but was equipotent to 1 alpha,25(OH)(2)D-3. More importantly, in the same assays, 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3 was more potent than 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 and was equipotent to 1 alpha,25(OH)(2)-19-nor-D-3. Also, the vitamin D receptor-mediated transcriptional activity or 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3 was almost equal to that of 1 alpha,25(OH)(2)-19-nor-D-3, but higher than that of 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3. This finding explains in part the greater in vitro biologic activities of 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3. In summary, our results indicate that 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3 and to a lesser extent 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 are potent 19-nor vitamin D-3 analogs, which suppress PTH secretion in bovine parathyroid cells and strongly inhibit clonal growth and induce differentiation of HL-60 cells in vitro. (C) 2000 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(99)00110-5
• 作为产物：
  描述：

  De-A,B-22-benzenesulphonyl-24,25-diol-cholestan-8-benzyloxymethyl ether 在 disodium hydrogenphosphate 、 sodium amalgam 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.25h， 生成 De-A,B-24-oxo-25-hydroxy-cholestan-8-benzyloxymethyl ether
  参考文献：
  名称：

  Synthesis and biological activities of the two C(23) epimers of 1α,23,25-trihydroxy-24-oxo-19-nor-vitamin D3: novel analogs of 1α,23(S),25-trihydroxy-24-oxo-vitamin D3, a natural metabolite of 1α,25-dihydroxyvitamin D3

  摘要：

  In a previous report. we indicated that 1 alpha,23(S).25-trihydroxy-23-oxovitamin D-3 [1 alpha,23(S).25(OH)(3)-24-oxo-D-3], a natural metabolite of 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] is almost equipotent to 1 alpha,25(OH)(2)D-3 in suppressing parathyroid hormone (PTH) secretion (Lee et al., 1997. Biochemistry 36, 9429-9437). Also, 1 alpha,23(S),25(OH)(3)-24-oxo-D-3 has been shown to possess only weak in vivo calcemic actions. Thus. vitamin D-3 analogs structurally related to 1 alpha,23(S),25(OH)(3)-24-oxo-D-3 may have therapeutic value. Furthermore. biologic activity studies of various synthetic analogs of 1 alpha,25(OH)(2)D-3 showed that the removal of carbon-19 (C-19) reduces the calcemic activity of 1 alpha,25(OH)(2)D-3. Therefore, in an attempt to produce vitamin D-3 analogs with a better therapeutic index, we synthesized C(23) epimers of 1 alpha,23,25(OH)(3)-24-oxo-19-nor-vitamin D-3 1 alpha,23,25(OH)(3)-24-oxo-19-nor-D-3]. The two epimers were compared to 1 alpha,25(OH)(2)-19-nor-D-3 and 1 alpha.25(OH)(2)D-3 in their ability to generate biologic activities in several in vitro assay systems. In the assay measuring the suppression of parathyroid hormone (PTH) secretion in bovine parathyroid cells, 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 was as potent as 1 alpha,25(OH)(2)-19-nor-D-3 but was less potent than 1 alpha,25(OH)(2)D-3. In the same assay 1 alpha,23(R)25(OH)(3)-24-oxo-19-nor-D-3 exhibited greater potency than 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3. In the assays measuring the ability of vitamin D compounds to inhibit clonal growth and to induce differentiation of human promyelocytic leukemia (HL60) cells, 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 was less potent than 1 alpha,25(OH)(2)-19-nor-D-3 but was equipotent to 1 alpha,25(OH)(2)D-3. More importantly, in the same assays, 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3 was more potent than 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 and was equipotent to 1 alpha,25(OH)(2)-19-nor-D-3. Also, the vitamin D receptor-mediated transcriptional activity or 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3 was almost equal to that of 1 alpha,25(OH)(2)-19-nor-D-3, but higher than that of 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3. This finding explains in part the greater in vitro biologic activities of 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3. In summary, our results indicate that 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3 and to a lesser extent 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 are potent 19-nor vitamin D-3 analogs, which suppress PTH secretion in bovine parathyroid cells and strongly inhibit clonal growth and induce differentiation of HL-60 cells in vitro. (C) 2000 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(99)00110-5