scholarly journals Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D3 Analogues and Their Stability to hCYP24A1-Dependent Catabolism

2021 ◽  
Vol 22 (21) ◽  
pp. 11863
Author(s):  
Fumihiro Kawagoe ◽  
Sayuri Mototani ◽  
Kaori Yasuda ◽  
Hiroki Mano ◽  
Toshiyuki Sakaki ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
Stereoselective Synthesis ◽  
Side Chain ◽  
Synthetic Route ◽  
Main Metabolite ◽  
Dihydroxyvitamin D3 ◽  
Synthetic Intermediates ◽  
24,25 Dihydroxyvitamin D3

Two 24-fluoro-25-hydroxyvitamin D3 analogues (3,4) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D3 side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24R)- and (24S)-24-fluoro-25-hydroxyvitamin D3 revealed that the C24-R-configuration isomer 4 was more resistant to CYP24A1-dependent metabolism than its 24S-isomer 3. The new synthetic route of the CYP24A1 main metabolite (24R)-24,25-dihydroxyvitamin D3 (6) and its 24S-isomer (5) was also studied using synthetic intermediates (30,31) in parallel.

scholarly journals Metabolism and pharmacokinetics of 24,25-dihydroxyvitamin D3 in the vitamin D3-replete rat.

1985 ◽  
Vol 260 (25) ◽  
pp. 13625-13630
Author(s):  
K Jarnagin ◽  
S Y Zeng ◽  
M Phelps ◽  
H F DeLuca
Keyword(s):  
Vitamin D3 ◽  
Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

The Effect of Vitamin D and Its Metabolites on Fracture Repair in Chicks

1983 ◽  
Vol 65 (4) ◽  
pp. 429-436 ◽  
Author(s):  
S. Dekel ◽  
R. Salama ◽  
S. Edelstein
Keyword(s):  
Vitamin D ◽  
Bone Formation ◽  
Vitamin D3 ◽  
Fracture Repair ◽  
Control Group ◽  
Clinical Implications ◽  
Torsional Stress ◽  
Active Vitamin ◽  
Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

1. One-day-old chicks were depleted of vitamin D. At 3 weeks their right tibiae, and those of a control group given vitamin D3, were fractured and pinned. After fracture the controls were kept on vitamin D3. Another group was left vitamin D-deficient. The remaining depleted chicks, divided into four groups, were given vitamin D3, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or a combination of 24,25(OH)2D3 and 1,25(OH)2D3. 2. The callus obtained after 9 and 14 days was subjected to torsional stress. The callus of chicks given vitamin D continuously showed the greatest resistance, whereas that of vitamin D-deficient chicks showed the smallest resistance. Repletion with either vitamin D3 or its metabolites increased the strength of the callus. Repletion with the combination of 24,25(OH)2D3 and 1,25(OH)2D3 produced the most marked results, in that the callus was even stronger than that of chicks replete with vitamin D3. 3. It is concluded that 24,25(OH)2D3 is essential for bone formation in addition to the known active vitamin D metabolite 1,25(OH)2D3, and the possible clinical implications of these findings are discussed.

Effects of vitamin D and diet magnesium on magnesium metabolism

1980 ◽  
Vol 239 (6) ◽  
pp. E515-E523 ◽  
Author(s):  
B. S. Levine ◽  
N. Brautbar ◽  
M. W. Walling ◽  
D. B. Lee ◽  
J. W. Coburn
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Tubular Reabsorption ◽  
Transport Processes ◽  
Separate Experiment ◽  
Dihydroxyvitamin D3 ◽  
Magnesium Metabolism ◽  
1,25 Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

Effects of 6-9 days of vitamin D3 (D3), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], or 1,24,25-trihydroxyvitamin D3 [1,24,25(OH)3D3] on Mg metabolism were studied in vitamin D-deficient (-D) rats. Mg absorption expressed as percent intake increased with 1,25(OH)2D3 and 1,24,25(OH)3D3. Urinary Mg (UMg) increased with no change in serum Mg (SMg) or Mg balance. 1,25(OH)2D3 was threefold more potent than 1,24,25(OH)3D3 in raising serum Ca and Mg absorption. In a separate experiment in pair-fed rats given D3, 1,25-(OH)2D3, or 1,24,25(OH)3D3, the diet contained either 0.03 or 0.2% Mg; 1,25(OH)2D3 and D3 lowered SMg after 3 days; UMg increased after 24 h to remain elevated. D3 and 1,25(OH)2D3 augmented Mg absorption; feeding 0.2% Mg lowered Mg absorption in -D animals. All sterols augmented Mg absorption in -D rats; both the earlier action of 1,25(OH)2D3 and 1,24,25(OH)3D3 suggests that 1-hydroxylation is necessary. Suppressed Mg absorption with 0.2% Mg in -D rats suggests two transport processes, with one vitamin D dependent. Higher UMg with decreased SMg with 1,25(OH)2D3 suggests reduced tubular reabsorption.

The ratio of serum 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 is predictive of 25-hydroxyvitamin D3 response to vitamin D3 supplementation

2011 ◽  
Vol 126 (3-5) ◽  
pp. 72-77 ◽  
Author(s):  
Dennis Wagner ◽  
Heather E. Hanwell ◽  
Kareena Schnabl ◽  
Mehrdad Yazdanpanah ◽  
Samantha Kimball ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
Dihydroxyvitamin D3 ◽  
Vitamin D3 Supplementation ◽  
24,25 Dihydroxyvitamin D3

Effect of vitamin D3, 25-hydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 on parathyroid hormone secretion

1987 ◽  
Vol 41 (1) ◽  
pp. 48-51 ◽  
Author(s):  
Larry K. Cantley ◽  
John B. Russell ◽  
Deborah S. Lettieri ◽  
Louis M. Sherwood
Keyword(s):  
Parathyroid Hormone ◽  
Vitamin D3 ◽  
Hormone Secretion ◽  
Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

Effect of vitamin D3 metabolites on calcium and phosphorus metabolism in chick embryos

1985 ◽  
Vol 248 (3) ◽  
pp. E281-E285 ◽  
Author(s):  
L. E. Hart ◽  
H. F. DeLuca
Keyword(s):  
Vitamin D ◽  
Embryonic Development ◽  
Vitamin D3 ◽  
Chorioallantoic Membrane ◽  
Sole Source ◽  
Chick Embryos ◽  
Dihydroxyvitamin D3 ◽  
Total Body Calcium ◽  
1,25 Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

The biochemical nature of the physiological defect found in chick embryos from hens supported on 1,25-dihydroxyvitamin D3 as their sole source of vitamin D is described. Vitamin D-deficient hens (44-wk-old) were divided into six groups of five and dosed daily for 19 wk with either 2.0 micrograms of 25-hydroxyvitamin D3, 2.0 micrograms of 24,24-difluoro-25-hydroxy-vitamin D3, 0.4 micrograms of 1,25-dihydroxyvitamin D3, 2.0 micrograms of 24,25-dihydroxyvitamin D3, 0.4 micrograms of 1,25-dihydroxyvitamin D3 plus 2.0 micrograms of 24,25-dihydroxyvitamin D3, or vehicle only. Normal embryonic development was found in eggs from hens given 25-hydroxyvitamin D3 or 24,24-difluoro-25-hydroxyvitamin D3, whereas embryos from hens given 1,25-dihydroxyvitamin D3, 24,25-dihydroxyvitamin D3, or their combination were abnormal and failed to hatch. Embryos from hens fed 1,25-dihydroxyvitamin D3 and/or 24,25-dihydroxyvitamin D3 had vitamin D deficiency: low bone ash, low plasma calcium, low total body calcium, and extremely high plasma phosphorus. Because the shell is the major source of calcium for the developing embryo, calcium transport from the shell to the embryos across the chorioallantoic membrane apparently fails, giving rise to the observed defects in embryonic development.

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