1α-Butyl-1β,25-dihydroxyvitamin 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-Butyl-1β,25-dihydroxyvitamin D3
• 英文别名: 1alpha-butyl-1beta,25-dihydroxyvitamin D3/1alpha-butyl-1beta,25-dihydroxycholecalciferol；(1R,3R,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-1-butyl-6-methylidenecyclohexane-1,3-diol
• 化学式: C₃₁H₅₂O₃
• 分子量: 472.752
• InChiKey: WWSMOPFEIPRNEI-UODWBYCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (1R,3R)-5-[(Z)-2-[(1R,3aR,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-1,2,3,3a,6,7-hexahydroinden-4-yl]ethenyl]-3-butyl-4-methylcyclohex-4-ene-1,3-diol 以 乙醇 为溶剂， 反应 432.0h， 以45%的产率得到1α-Butyl-1β,25-dihydroxyvitamin D3
  参考文献：
  名称：

  Syntheses of 1-Alkyl-1,25-dihydroxyvitamin D3

  摘要：

  1-Allkylated analogs of 1 alpha,25-(OH)(2)D-3 were synthesized to investigate the effect of the alkyl group on the A-ring conformation and the biological potency. The analogs were synthesized via two routes. In the first approach, alkylation of 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) adduct of 1-oxopro-vitamin D (4) was used as the key step to synthesize 1 beta-methyl-1 alpha,25-dihydroxyprovitamin D-3 (OH)(2)D-3 (16a) efficiently and stereoselectively. The photolysis of the provitamin D (16a), however, gave the desired previtamin D (17a) only as a minor product (<5%) and an unusual 1,10-bond cleavage product (18a) occurred in high yield (79%). As an alternative C(1)-epimeric pairs of 1-alkyl-1,25-(OH)(2)D-3 were synthesized conveniently from 25-hydroxy-1-oxoprevitamin D-3 (19) by reaction with an alkyllithium followed by thermal isomerization. In the alkylation, the alkyllithium attacked the ketone preferentially from the side of the 3 beta-hydroxyl group to afford the 1 beta-alkyl-1 alpha-hydroxy epimer in a 1.6-2.7 to 1 ratio over the 1 alpha-alkyl-1 beta-hydroxy isomer. Introduction of a 1 beta-methyl group to 1 alpha,25-(OH)(2)D-3, shifted the equilibrium between the two chair conformations of the A-ring preferentially to the side of the alpha-form (4:1) and reduced considerably the activity to bind to the VDR.

  DOI：

  10.1021/jo00111a047

文献信息

• Syntheses of 1-Alkyl-1,25-dihydroxyvitamin D3
  作者：Hiroki Ishida、Masato Shimizu、Keiko Yamamoto、Yukiko Iwasaki、Sachiko Yamada、Kentaro Yamaguchi

  DOI：10.1021/jo00111a047

  日期：1995.3

  1-Allkylated analogs of 1 alpha,25-(OH)(2)D-3 were synthesized to investigate the effect of the alkyl group on the A-ring conformation and the biological potency. The analogs were synthesized via two routes. In the first approach, alkylation of 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) adduct of 1-oxopro-vitamin D (4) was used as the key step to synthesize 1 beta-methyl-1 alpha,25-dihydroxyprovitamin D-3 (OH)(2)D-3 (16a) efficiently and stereoselectively. The photolysis of the provitamin D (16a), however, gave the desired previtamin D (17a) only as a minor product (<5%) and an unusual 1,10-bond cleavage product (18a) occurred in high yield (79%). As an alternative C(1)-epimeric pairs of 1-alkyl-1,25-(OH)(2)D-3 were synthesized conveniently from 25-hydroxy-1-oxoprevitamin D-3 (19) by reaction with an alkyllithium followed by thermal isomerization. In the alkylation, the alkyllithium attacked the ketone preferentially from the side of the 3 beta-hydroxyl group to afford the 1 beta-alkyl-1 alpha-hydroxy epimer in a 1.6-2.7 to 1 ratio over the 1 alpha-alkyl-1 beta-hydroxy isomer. Introduction of a 1 beta-methyl group to 1 alpha,25-(OH)(2)D-3, shifted the equilibrium between the two chair conformations of the A-ring preferentially to the side of the alpha-form (4:1) and reduced considerably the activity to bind to the VDR.