1-Oxo-25-hydroxyprevitamin D₃ | 66760-28-9

• 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: 1-Oxo-25-hydroxyprevitamin D₃
• 英文别名: 25-Hydroxy-1-oxoprevitamin D3；(5R)-3-[(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]-5-hydroxy-2-methylcyclohex-2-en-1-one
• CAS: 66760-28-9
• 化学式: C₂₇H₄₂O₃
• 分子量: 414.629
• InChiKey: FKHXIOLWTIFLGY-CHGIVTTMSA-N

物化性质

• 沸点：
  566.5±50.0 °C(Predicted)
• 密度：
  1.115±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-Oxo-25-hydroxyprevitamin D₃ 在 sodium tetrahydroborate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 4.0h， 生成 骨化三醇
  参考文献：
  名称：

  Studies of vitamin D (calciferol) and its analogs. 45. Studies on the A-ring diastereomers of 1.alpha.,25-dihydroxyvitamin D3

  摘要：

  The three A-ring diastereomers 3b (compound HL), 4a (compound HJ), and 4b (compound HH), of the steroid hormone 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2-D3, 3a, compound C) have been synthesized and biologically evaluated. (R)-Carvone was converted in seven steps to the enantiomerically pure A-ring enyne 7a. Palladium-catalyzed cross-coupling of the latter with the CD-ring triflate 8 resulted in silyloxy dienyne 10, which was converted in three steps to 1beta,25-(OH)2-3-epi-D3 (4b). Oxidation of the latter with Dess-Martin reagent afforded trienone 6c, which upon reduction with sodium borohydride followed by thermolysis generated the 1alpha-epimer 4a. An identical sequence converted 1alpha,25-(OH)2-D3 to its 1beta-epimer 3b via trienone 5c. Reduction of the latter with sodium triacetoxyborohydride followed by thermal isomerization regenerated the hormone 3a. Relative competitive indices (RCls) of these analogues, which reflect their ability to bind to the chick intestinal nuclear receptor under in vitro conditions, were determined. Analogues 3b, 4a, and 4b had RCI values of 0.8 +/- 0.1 %, 24.0 +/- 4.5 %, and 0.22 +/- 0.01 %, respectively, in comparison to 1alpha,25-(OH)2-D3 whose value is 100% by definition. In addition, in vivo biological evaluation of these analogues was performed to determine their ability to induce intestinal calcium absorption (ICA) and bone calcium mobilization (BCM) in vitamin D deficient chicks. Analogue 4a was effective in stimulating ICA and BCM whereas analogues 3b and 4b exhibited little potency in eliciting these biological effects.

  DOI：

  10.1021/jo00059a048
• 作为产物：
  描述：

  骨化三醇 在 戴斯-马丁氧化剂 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以88%的产率得到1-Oxo-25-hydroxyprevitamin D₃
  参考文献：
  名称：

  Studies of vitamin D (calciferol) and its analogs. 45. Studies on the A-ring diastereomers of 1.alpha.,25-dihydroxyvitamin D3

  摘要：

  The three A-ring diastereomers 3b (compound HL), 4a (compound HJ), and 4b (compound HH), of the steroid hormone 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2-D3, 3a, compound C) have been synthesized and biologically evaluated. (R)-Carvone was converted in seven steps to the enantiomerically pure A-ring enyne 7a. Palladium-catalyzed cross-coupling of the latter with the CD-ring triflate 8 resulted in silyloxy dienyne 10, which was converted in three steps to 1beta,25-(OH)2-3-epi-D3 (4b). Oxidation of the latter with Dess-Martin reagent afforded trienone 6c, which upon reduction with sodium borohydride followed by thermolysis generated the 1alpha-epimer 4a. An identical sequence converted 1alpha,25-(OH)2-D3 to its 1beta-epimer 3b via trienone 5c. Reduction of the latter with sodium triacetoxyborohydride followed by thermal isomerization regenerated the hormone 3a. Relative competitive indices (RCls) of these analogues, which reflect their ability to bind to the chick intestinal nuclear receptor under in vitro conditions, were determined. Analogues 3b, 4a, and 4b had RCI values of 0.8 +/- 0.1 %, 24.0 +/- 4.5 %, and 0.22 +/- 0.01 %, respectively, in comparison to 1alpha,25-(OH)2-D3 whose value is 100% by definition. In addition, in vivo biological evaluation of these analogues was performed to determine their ability to induce intestinal calcium absorption (ICA) and bone calcium mobilization (BCM) in vitamin D deficient chicks. Analogue 4a was effective in stimulating ICA and BCM whereas analogues 3b and 4b exhibited little potency in eliciting these biological effects.

  DOI：

  10.1021/jo00059a048

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.