La -hydroxycholecalciferol

Therapeutic Function Calcium Regulator, Vitamin D Chemical Name 9,10-Secocholesta-5,7,10(19)-triene-1,3-diol Common Name la-Hydroxycholecalciferol 1a-Hydroxyvitamin D3 Structural Formula ... 

Preparation of la-hydroxycholecalciferol a solution of 13.5 mg of 1a,3/3-dihydroxypro-vitamin D3 in 200 ml of ether is allowed to stand still in the dark at room temperature in an argon gas atmosphere for 2 weeks. During this period, the position of the maximum ultraviolet absorption is shifted from 260 m/u to 264 m/u, and the absorption intensity becomes... 

Vitamin D preparations that are available include er-gocalciferol (also termed calciferol, or vitamin D2), cholecalciferol (vitamin D3), alfa-calcidol (la-hydroxycholecalciferol) and calcitriol (1,25-hydroxycholcalciferol). 

The term vitamin D is used for a range of compounds which possess the property of preventing or curing rickets. They include ergocalciferol (calciferol, vitamin D ), chole-calciferol (vitamin Dg), dihydrotachysterol, alfacalcidol (la-hydroxycholecalciferol) and calcitriol (1,25-dihydroxycholecalciferol). 

Cholecalciferol 25-hydroxylase is not restricted to the liver kidneys, skin, and gut microsomes also have a cytochrome P450 -dependent enzyme that catalyzes the 25-hydroxylation of cholecalciferol and la-hydroxycholecalciferol, hut not ergocalciferol. Although there is some evidence that calcitriol can reduce the activity of calciferol 25-hydroxylase, it is not known whether this is physiologically important the major factor controlling 25-hydroxylation is the rate of uptake of cholecalciferol into the liver. It is the fate of calcidiol in the kidneys that provides the most important regulation of vitamin D metabolism (Wikvall, 2001). 

Three conditions associated with defective 1-hydroxylation of calcidiol can aU be treated by the administration of either calcitriol itself or la-hydroxycholecalciferol, which is a substrate for 25-hydroxylation in the liver forming calcitriol ... 

A mixture of 25-fluoro-la-hydroxycholecalciferol and the 1 a-hydroxy-A -and -A -compounds (270) was obtained from the reaction of the diacetate (269)... 

Subsequently there was introduced a la-hydroxylated form (la-hydroxycholecalciferol) alfacalcidol (One-Alpha), that requires only hepatic hydroxylation to become the highly active la-25-dihydroxycholecalciferol (calcitriol). Alfacalcidol (and of course calcitriol) is therefore effective in renal failure since the defective renal hydroxylation stage is bypassed. Its extraordinary potency and efficacy is indicated by the usual adult maintenance dose, often only 0.25-1 micrograms/d. 

A new synthesis of la-hydroxycholecalciferol (la-hydroxy-vitamin D3) from cholesterol employs transformations in rings A and B which differ only in detail from an earlier sequence for introduction of the la-hydroxy-group the la,2a-epoxy-3j8,6j8-diol derivative (382) was the key intermediate, allowing regeneration of... 

Oxidation of la-hydroxycholecalciferol and la,25-dihydroxycholecalciferol with Mn02 gave the corresponding 1 -oxo-previtamins which could be reduced with LiAlH4 at —25 °C in each case to give a mixture of la-hydroxy- and IjS-hydroxy-previtamins in which the IjS-epimers (285) and (286) predominated. Thermal equilibration allowed the isolation of the 1/3-hydroxy-cholecalciferol and l/ ,25-dihydroxycholecalciferol. A similar independent synthesis of 1/3-hydroxycholecalciferol employed NaBH4 for the reduction... 

Recent advances in the chemistry and biology of vitamin D have been reviewed.The C,D-fragment (208) became readily available from the degradation of cholesterol through the A -compK)und (207). Syntheses (formally total) of la-hydroxycholecalciferol and la-hydroxyprecholecal-ciferol employed the key intermediate (208). A key step in the degradation... 

A synthesis of 26,26,26,27,27,27-hexafluoro-25-hydroxychoIecalciferoI has been reported, and the two side-chain constructions used are shown in Scheme 7 188 2/3-Fluoro-la-hydroxycholecalciferol was synthesized by standard procedures from the dihydroxyfluorocholest-5-ene (216) which was obtained from the epoxide (215) by treatment with KHF2-ethylene glycol. Syntheses of... 

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