Of vitamin D analogues

Vitamin rarely occurs in plants. However, Solanumglaucophjllum Solanum malacoyyhn Cestrum diumum and TrinetumJlavescens have been shown to contain water-soluble glycosides of vitamin D analogues with 1 a,25-dihydroxy-vitarnin D activity (16—22). The vitamin D content in various plant and animal materials is shown in Table 3. Vitamin D occurs naturally in all animals (24). 

Scheme 8C.20. Symmetry -assisted enantiospecific synthesis of A-ring of Vitamin D analogues based on asymmetric ene cyclization.

Van de Kerkhof, P.C.M., Biological activity of vitamin D analogues in the skin, with special reference to antipsoriatic mechanisms, Br. J. Dermatol., 132, 675, 1995. 

The first line of treatment is usually the application of topical products, ranging from over-the-counter products to topical steroids. Emollients may be used to reduce dryness and scaling, as well as reducing the hyperproliferation associated with plaque psoriasis. The use of vitamin D analogues, tazarotene, dithranol or coal tar preparations aims to lessen or remove the patient s scaly plaques. However, excess use can irritate the skin and their use is not recommended for the more irritant forms of psoriasis. Tar baths and tar shampoos (containing coal tar) may help with managing the condition. Treatment, if nonirritating, should be continued for 4-6 weeks and thereafter assessed. Emollients... 

Brown AJ (2001) Therapeutic uses of vitamin D analogues. American Journal of Kidney Disease 38, S3-S19. 

Of 19 chronic hemodialysis patients taking a combination of alfacalcidol and calcitriol for 12 months, six had increased bone resorption, six had reduced bone resorption, and seven had no change. Histologically documented aggravation of hyperparathyroidism was associated with a statistically significant increase in plasma concentrations of phosphate and parathyroid hormone. The administration of vitamin D analogues may therefore be either beneficial or noxious depending on whether or not induced hyperphosphatemia is adequately prevented (55). 

Other recent studies have examined the effects of substituents on the photochemistry of vitamin D analogues - . ... 

Verstuyf, A. (2000) Recent developments in the use of vitamin D analogues. Expert Opinion on Investigational Drugs, 9, 443—455. 

Carlberg, C. (2003) Molecular basis of the selective activity of vitamin D analogues. Journal of Cellular Biochemistry, 88, 274-281. 

Reviews on the synthesis and structure-function relationships of vitamine D analogues Bouillon R, Okamura WH, Norman AW (1995) Endocrine Reviews 16 200 Dai H, Posner GH (1994) Synthesis 1383... 

STRUCTURE-ACTIVITY RELATIONSHIPS OF NATURALLY OCCURRING ACTIVE FORMS OF VITAMIN D ANALOGUES... 

D2 and D ) on 1 (X(OH)2 D3 and 1 (X,25(OH)2 D3 may induce remarkable changes in the biological activities and the analysis of structure-activity relationships among these compounds should be important to develop vitamin D analogues for clinical use. The chemical structures of active forms of vitamin D analogues are illustrated in Fig. (1). 

We report here the synthesis, biological activities and metabolism of the active forms of naturally occurring vitamin D analogues, especially active form of vitamin D4 (1comparison with those of l(X,25(OH)2D3. In addition, we introduce application of the synthetic procedure developed for the preparation of active forms of vitamin D analogues described here to the synthesis of biologically active natural steroids and the intermediates in ergosterol biosynthesis. 

The active forms of vitamin D analogues (1-14) were synthesized by the coupling of the steroid moiety [20] with the corresponding phenyl sulfone derivatives [21] to constitute the side chain part followed by the UV irradiation of the provitamins and the subsequent thermal isomerization of the previtamin D derivatives [22], These active forms of vitamin D analogues were also prepared through the cyclovitamin D derivatives [23]. 

Okano et al. assessed the structure-activity relationships of the active forms of vitamin D analogues especially with respect to the structural differences in the configuration of the methyl group at C-24 position and the role of a double bond between C-22/C-23 in the side chain of la,25(OH)2D analogues [33]. 

The synthetic procedure developed for the preparation of active fonns of vitamin D analogues was applied to the synthesis of various natural steroids by the reaction of steroid moieties with phenyl sulfone derivatives described here. 

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