Previtamin D | 163011-08-3

• 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: Previtamin D
• CAS: 163011-08-3
• 化学式: C₂₈H₄₆O₃
• 分子量: 430.671
• InChiKey: QBEUYDPJMWCIEY-FOZZKVSRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.09
• 重原子数：
  31.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  60.69
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  Previtamin D 以 乙醇 为溶剂， 反应 288.0h， 生成 1α,25-Dihydroxy-1β-methylvitamin 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
• 作为产物：
  描述：

  Provitamin D 以 乙醇 为溶剂， 反应 0.08h， 以79%的产率得到(4R)-4-hydroxy-5-[(1S,10R,11R)-11-[(2R)-6-hydroxy-6-methylheptan-2-yl]-6,10-dimethyl-5-tetracyclo[8.3.0.02,4.03,7]tridec-5-enyl]pentan-2-one
  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

• New photoisomerization of provitamin D caused by hydroxylation at C(1)
  作者：Sachiko Yamada、Hironobu Ishizaka、Hiroki Ishida、Keiko Yamamoto

  DOI：10.1039/c39950000423

  日期：——

  1α-Hydroxyprovitamin D is found to undergo a new photochemical isomerization cascade initiated by the 1,10-bond cleavage in addition to the normal electrocyclic B-ring opening and this new isomerization becomes the major pathway when a methyl group is present in the 1β-position.

  1α-羟基维生素D被发现会经历新的光化学异构化级联反应，该反应由1,10键断裂引发，此外还有正常的电循环B环打开，当1β位存在甲基时，这种新的异构化反应成为主要途径。