Calciferol synthesis

Calcidiol la-hydroxylase is not restricted to the kidney, but is also found in placenta, bone cells (in culture), mammary glands, and keratinocytes. The placental enzyme makes a significant contribution to fetal calcitriol, but it is not clear whether the calcidiol 1-hydroxylase activity of other tissues is physiologically significant or not. Acutely nephrectomized animals given a single dose of calcidiol do not form any detectable calcitriol, but there is some formation of calcitriol in anephric patients, which increases on the administration of cholecalciferol or calcidiol. However, thus extrarenal synthesis is not adequate to meet requirements, so that osteomalacia develops in renal failure (Section 3.4.1). The enzyme is inhibited, or possibly repressed, by strontium ions this is the basis of strontium-induced vitamin D-resistant rickets, which responds to the administration of calcitriol or la-hydroxycalciol, but not calciferol or calcidiol (Omdahl and DeLuca, 1971). 

The Julia reductive elimination is a good choice when trying to prepare mono-, 1,1-di- and E-l,2-disubstituted alkenes. This application has been demonstrated, for example, in the preparation of a key intermediate in the synthesis of calciferol (Eq. 167).305 The alternative Wittig olefination approach failed due to the difficulties encountered in the preparation of the corresponding sterically hindered phosphonium halide.305... 

Chapelo, C. B., P. Hallett, B. Lythgoe, I. Waterhouse, and P. W. Wright Calciferol and its Relatives. Part 19. Synthetic Applications of Cyclic Orthoesters Stereospecific Synthesis of a Bicyclic Alcohol Related to the Vitamins D. J. Chem. Soc. Perkin 11977,1211. 

Harmeyer, J., and H. F. DeLuca Calcium Binding Protein and Calcium Absorption after Vitamin D Administration. Arch. Biochem. Biophys. 133, 247 (1969). Harrison, I. T., and B. Lythgoe Calciferol and its Relatives. Part III. Partial Synthesis of Calciferol and of Epicalciferol. J. Chem. Soc. (London) 1958, 837. Harrison, R. G., B. Lythgoe, and P. W. Wright Calciferol and its Relatives. Part XVIII. Total Synthesis of la-Hydroxyvitamin D3. J. Chem. Soc. Perkin I 1974, 2654. 

A group of fat-soluble vitamins. Cholecalciferol (vitamin D3) can be obtained from dietary sources and can also be produced in the skin by the action of sunlight on 7-dehydrocholesterol. Another vitamin D (ergocalciferol, vitamin Dj) can be obtained from plants. Cholecalciferol undergoes two hydroxylation steps in the body in its conversion to its active form, 1,25-dihydroxy-cholecalciferol. The C-2S hydroxylation takes place in the liver and this is followed by the C-I hydroxylation which takes place in the kidneys. The rate of synthesis of 1,25-dihydroxychole-calciferol is thought to be controlled by the circulating parathyroid hormone levels. 

---