Vitamin D synthesis

An important application of the allylic bromination-dehydrobromination approach is the formation of the A -diene system e.g. 110) in vitamin D synthesis. Dehydrobromination of the A -7-bromo system in the presence of mercuric chloride gives a high yield of A -diene. ... 

For example, elderly patients living in musing homes will not be able to meet vitamin D requirements and will need supplementation. Vitamin D deficiency is common in elderly patients owing to decreased exposure to sunlight and subsequent decreased vitamin D synthesis in the skin, decreased gastrointestinal absorption of vitamin D, and reduction in vitamin D3 synthesis. Individuals living in northern climates also have decreased exposure to sunlight and are less likely to achieve vitamin D requirements. 

Vitamin D is a secosteroid present in the diet but is mainly produced non-enzymatically in the skin from cholesterol under the influence of ultraviolet light. Vitamin D synthesis is promoted by PTH. This is vitamin D3 or cholecalciferol. Vitamin D2, ergocalcif-erol is found in vegetables. Both forms of vitamin D... 

Vitamin D is synthesized in the skin in the presence of ultraviolet light, and it is unusual to become dependent on dietary intake except when exposed to inadequate UV light. The active form of vitamin D is 1,25-dihydroxycholecalciferol (1,25-OHCC), also termed calcitriol. For vitamin D synthesis, cholecal-ciferol (also termed vitamin D3) is synthesized in the skin from cholesterol via 7-dehydrocholesterol, and is 25-hydroxylated in the liver and 1-hydroxylated in the kidney. Dietary vitamin D is actually a mixture of sterols which includes 7-dehydrocholesterol, and is mainly found in fish and eggs. 

Figure 26.29. Vitamin D Synthesis. The pathway for the conversion of 7-dehydrocholesterol into vitamin D3 and then into calcitriol, the active hormone.

The most common cause of hyperphosphatemia is a decrease in urinary phosphorus excretion secondary to decreased glomerular filtration rate. ° Retention of phosphorus decreases vitamin D synthesis and induces hypocalcemia, which leads to an increase in PTH. This physiologic response inhibits further tubular reabsorption of phosphorus to correct hyperphosphatemia and normalize serum calcium concentrations. Patients with excessive exogenous phosphorus administration or endogenous intracellular phosphorus release in the setting of acute renal failure may develop profound hyperphosphatemia. Severe hyperphosphatemia is commonly encountered in patients with chronic kidney disease, especially those with GFRs less than 15 mL/ min per 1.73 m (see Chap. 44). 

Renal disease with deficient 1,25(OH) vitamin D synthesis can be treated with calcitriol, with careful monitoring of serum calcium and creatinine. This compound has a 6-hour half-life and a rapid onset of action. Patients with renal dysfunction should decrease oral... 

PTH also acts to increase absorption of calcium ion by the small intestine. It does this indirectly by promoting the formation of active vitamin D in the kidney. PTH acts on the final, rate-limiting step in vitamin D synthesis, the formation of 1,25-dihydroxycholecalciferol in the kidney. If PTH is low, formation of the inactive derivative, 24,25-dihydroxycholecalciferol, is stimulated instead. Vitamin D acts on intracellular receptors in the small intestine to increase transcription of genes encoding calcium uptake systems, to up-regulate their expression. 

J. Yanagisawa, and S. Kato (1997). 25-Hydroxy vitamin Dj la-hydroxylase and vitamin D synthesis. Science 111, 1827-1830. 

The Wittig reaction published in 1954 [56] played a fundamental role in the Braunschweig synthesis of vitamin D3. 7t seems appropriate to point out that, without the Wittig reaction, no completed vitamin-D synthesis would lie before us today [57]. 

A useful building block 519 for vitamin D synthesis was prepared by reaction of the alkenyloxirane 517 [195], Under usual conditions of the elimination, both the dienyl alcohol 519 and the unsaturated ketone 520 were formed in equal amounts. Radinov and co-workers discovered an interesting and remarkable effect of the addition of fluorinated alcohols, such as l,3-bis-(l,l,l,3,3,3-hexafluoro-2-hydroxypropyl)benzene or perfluoro-t-butyl alcohol as a proton source, on the chemoselectivity, and the desired 519 was obtained with nearly complete chemos-electivity with these additives [195], They suggest that rapid protonation of the intermediate alkoxide 518 with these alcohols seems to be important. 

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