2β-methoxy-cholesta-5,7-diene-1α,3β,25-triol | 220294-62-2

• 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: 2β-methoxy-cholesta-5,7-diene-1α,3β,25-triol
• CAS: 220294-62-2
• 化学式: C₂₈H₄₆O₄
• 分子量: 446.671
• InChiKey: USOSDDZRAHQKHP-FLLSWAELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.02
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  69.92
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2β-methoxy-cholesta-5,7-diene-1α,3β,25-triol 生成 2β-methoxy-calcitriol
  参考文献：
  名称：

  Synthesis and biological activities of 2β-chloro-, 2β-fluoro-, and 2β-methoxy-1α,25-dihydroxyvitamin D3

  摘要：

  Using 1 alpha,2 alpha-oxido-cholesta-5,7-diene-3 beta,25-diol (2) as a starting material, the provitamins of calcitriol with an additional 2 beta-chloro-, 2 beta-flouro, and 2 beta-methoxy-substituent (3,4,5) are obtained by transdiaxial opening of the oxirane ring with nucleophiles. An efficient irradiation process is described and used for the synthesis of the 2 beta-substituted calcitriols NS2, (2 beta-Cl), NS6 (2 beta-F), and NS7 (2 beta-OCH3). The affinity of these three vitamin D-3 derivatives to the vitamin D receptor (VDR) and was determined. These three A-ring derivatives of 1,25(OH)(2)D-3 were further tested for their proliferation-inhibitory and anti-adipogenic activity and gene regulatoric activity in the vitamin D-3-sensitive, murine, mesenchymal cell line C3H10T1/2. The VDR-affinity of the 2 beta-chloro derivative, NS2 (2 beta-Cl), was identical to 1,25(OH)(2)D-3 and its vitamin D binding protein (DBP)-affinity was in the range of 1,25(OH)(2)D-3. NS2 inhibited the proliferation of C3H10T1/2(BMP-4)-cells in the presence of fetal calf serum (FCS) 9 times, and, in the absence of FCs, 111 times lower, as compared with 1,25(OH)(2)D-3. The ID50 dose of adipogenesis-inhibition of NS2 was 13 times higher than the ID50 dose of 1,25(OH)(2)D-3. NS6 (2 beta-F) displayed a slightly higher affinity than 1,25(OH)(2)D-3 to the VDR and the DBP-affinity. The proliferation-inhibitory activity in the presence of FCS was 90 times higher, as compared with 1,25(OH)(2)D-3. NS6 showed an 5 times higher potency to inhibit (pre)adipocyte-differentiation in C3H10T1/2(BMP-4)-cells than 1,35(OH)(2)D-3. NS7 (2 beta-OCH3) showed the lowest VDR-affinity and the highest DBP-affinity of the tested substances, as compared with 1,25(OH)(2)D-3 (11 times lower and 35 times higher respectively). Its proliferation-inhibitory activity in the FCS-free medium was 9 times and in the FCS-containing assay 67 times lower in comparison with 1,25(OH)(2)D-3. A 1250 times higher NS7-dose was needed to reach the anti-adipogenic potency of 1,25(OH)(2)D-3. All tested substances displayed a similar ability to activate a vitamin D responsive element-regulated reporter gene compared to 1,25(OH)(2)D-3 (NS2 and NS6: 1.3 times higher activity; NS7: 1,4 times lower activity). (Steroids 63:633-643, 1998). (C) 1998 by Elsevier Science Inc.

  DOI：

  10.1016/s0039-128x(98)00072-5
• 作为产物：
  描述：

  3β-acetoxy-1α,2α-oxido-cholesta-5,7-dien-25-ol 在 potassium carbonate 、 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 1.17h， 生成 2β-methoxy-cholesta-5,7-diene-1α,3β,25-triol
  参考文献：
  名称：

  Synthesis and biological activities of 2β-chloro-, 2β-fluoro-, and 2β-methoxy-1α,25-dihydroxyvitamin D3

  摘要：

  Using 1 alpha,2 alpha-oxido-cholesta-5,7-diene-3 beta,25-diol (2) as a starting material, the provitamins of calcitriol with an additional 2 beta-chloro-, 2 beta-flouro, and 2 beta-methoxy-substituent (3,4,5) are obtained by transdiaxial opening of the oxirane ring with nucleophiles. An efficient irradiation process is described and used for the synthesis of the 2 beta-substituted calcitriols NS2, (2 beta-Cl), NS6 (2 beta-F), and NS7 (2 beta-OCH3). The affinity of these three vitamin D-3 derivatives to the vitamin D receptor (VDR) and was determined. These three A-ring derivatives of 1,25(OH)(2)D-3 were further tested for their proliferation-inhibitory and anti-adipogenic activity and gene regulatoric activity in the vitamin D-3-sensitive, murine, mesenchymal cell line C3H10T1/2. The VDR-affinity of the 2 beta-chloro derivative, NS2 (2 beta-Cl), was identical to 1,25(OH)(2)D-3 and its vitamin D binding protein (DBP)-affinity was in the range of 1,25(OH)(2)D-3. NS2 inhibited the proliferation of C3H10T1/2(BMP-4)-cells in the presence of fetal calf serum (FCS) 9 times, and, in the absence of FCs, 111 times lower, as compared with 1,25(OH)(2)D-3. The ID50 dose of adipogenesis-inhibition of NS2 was 13 times higher than the ID50 dose of 1,25(OH)(2)D-3. NS6 (2 beta-F) displayed a slightly higher affinity than 1,25(OH)(2)D-3 to the VDR and the DBP-affinity. The proliferation-inhibitory activity in the presence of FCS was 90 times higher, as compared with 1,25(OH)(2)D-3. NS6 showed an 5 times higher potency to inhibit (pre)adipocyte-differentiation in C3H10T1/2(BMP-4)-cells than 1,35(OH)(2)D-3. NS7 (2 beta-OCH3) showed the lowest VDR-affinity and the highest DBP-affinity of the tested substances, as compared with 1,25(OH)(2)D-3 (11 times lower and 35 times higher respectively). Its proliferation-inhibitory activity in the FCS-free medium was 9 times and in the FCS-containing assay 67 times lower in comparison with 1,25(OH)(2)D-3. A 1250 times higher NS7-dose was needed to reach the anti-adipogenic potency of 1,25(OH)(2)D-3. All tested substances displayed a similar ability to activate a vitamin D responsive element-regulated reporter gene compared to 1,25(OH)(2)D-3 (NS2 and NS6: 1.3 times higher activity; NS7: 1,4 times lower activity). (Steroids 63:633-643, 1998). (C) 1998 by Elsevier Science Inc.

  DOI：

  10.1016/s0039-128x(98)00072-5