Vitamin synthetic analogs

It seems worthy to comment on the name second generation lazaroid. Fooking at the structure of U-83836E, one may wonder why this compound is associated with 12-amino steroids at all, whereas it is just another model of a-tocopherol and should be compared not with first generation lazaroids but with the synthetic analogs of vitamin E (see above). 

Calcipotriene (Dovonex) is a synthetic vitamin D analog used for mild to moderate plaque psoriasis. Improvement is usually seen within 2 weeks of treatment, and approximately 70% of patients demonstrate marked improvement after 8 weeks. Adverse effects occur in about 10% of patients and include lesional and perilesional burning and stinging. Calcipotriene 0.005% cream, ointment, or solution is applied one or two times a day (no more than 100 g/wk). 

Phytonadione (vitamin K- ) is a lipid-soluble synthetic analog of vitamin K. 

Mechanism of Action A synthetic vitamin Dj analog that regulates skin cell (kerat-inocyte) production and development. Therapeutic Effect Preventing abnormal growth and production of psoriasis (abnormal kerafinocyte growth). Pharmacokinetics Minimal absorption through intact skin. Metabolized in liver. 

Doxercalciferol, the active ingredient in Hectorol, is a synthetic vitamin D analog that undergoes metabolic activation in vivo to form 1 (alpha),25-dihydroxyvitamin D2 (l(alpha),25-(OH)2D2), anaturally occurring, biologically active form of vitamin D2. Hectorol is available as soft... 

The examples discussed in this paper demonstrate that Pd-catalyzed coupling reactions can be successfully utilized in the convergent (modular) synthesis of vitamin D-active compounds. The new synthetic routes open an efficient and highly selective access to a variety of vitamin D analogs. While reliable methods exist today for the construction of the triene system and for the synthesis of the ring A precursors, the search for efficient total synthetic approaches to the CD building blocks still remain a challenging task for the future. 

In vitro, and in experimental animals, vitamin A has anticancer action related to its role in modulating gene expression and tissue differentiation. It retards the initiation and growth of some experimental tumors. However, it only shows these effects at toxic levels, and a number of synthetic analogs. 

Figure 4.1. Vitamin E vitamers, tocopherois and tocotrienois, and the synthetic water-soluble vitamin E analog, Trolox. Relative molecular masses (Mr) a-tocopherol, 430.7 (acetate 488.8, succinate 546.8) , 6-tocopherol, 419.7 y-tocopherol, 416.7 5-tocopherol, 402.7 a-tocotrienol, 424.7 , 6-tocotrienol, 410.7 y-tocotrienol, 410.7 5-tocotrienol, 396.7 and Trolox, 250.3.

Guyton KZ, Kensler TW, and Posner GH (2001) Cancer chemoprevention using natural vitamin D and synthetic analogs. Annual Reviews ofPharmacology and Toxicology 41, 421-42. 

Interest in vitamin A and its synthetic analogs as a potential factor in the prevention and treatment of certain types of cancer has been growing. In addition, there is evidence that vitamin A may be related to pollutant toxicity. Recent epidemiological studies in humans with a sample of 8000 men in Chicago showed a low lung cancer incidence in those with a high vitamin A level in the diet, while the incidence was higher in those people with a low dietary vitamin A. Experimental studies show that rats exposed to PCB, DDT, and dieldrin caused a 50% reduction in liver vitamin A store. In another study, rats deficient in retinol were shown to have a lowered liver cytochrome P-450 activity. The effect of vitamin A deficiency on MFO enzymes, however, depends on several factors such as substrate, tissue, and animal species. 

Several synthetic vitamin D analogs have been prepared and their activities investigated. Of particular importance for potential anti-cancer and immune supression drugs, are vitamin D compounds whose bone calcium activity is low and cell differentiation activity is high. Compound 1 and 2 are traditional vitamin D structures with high bone calcemic activity (calcium homeostasis) and only modest cell differentiation activity. 

Steinmeyer, A. et al. (2000) New synthetic vitamin D analogs with antiproliferative activities. Current Pharmaceutical Design, 6, 767-789. 

Whereas retinol and its esters (which are the forms of vitamin A in foods) are toxic at higher intake or supplement levels, synthetic analogs may avoid this toxicity, examples being derivatives of retinoic acid. A componnd known as 13-cis-retinoic acid has been noted to reverse premahgnant lesions in the case of certain kinds of... 

Calcipotriene is an antipsoriatic agent. It is a synthetic vitamin Dj analog. In a manner similar to vitamin D, calcipotriene regulates skin cell production and development, thereby modifying the abnormal growth and production of kerati-nocytes, responsible for the scaly red patches characteristic of psoriasis (see Figure 105). Calcipotriene is indicated in the treatment of plaque psoriasis. Scalp solution topical treatment of chronic, moderately severe psoriasis of the scalp. 

Secocholesia-5,7,10(19)-iriene-I,3-diol lo-hydroxyvi tamin D3 la-OH-CC aifacalcidot Alfarol Alpha D EinsAlpha Etalpha One-Alpha. C H Ogl mol wt 400.65. C 80.94%, H 11,07%, O 7.99%, Synthetic analog of calcitriol, q.v.. the hormonal form of vitamin D3, which shows identical potency with respect to stimulation of intestinal calcium absorp-... 

The elucidation of the biochemistry of the vitamin D endocrine system has led to a renewed interest in the synthetic aspects of the field. Because of the limited availability of vitamin D metabolites from natural sources, the production of large quantities of metabolites and analogs is essential for detailed biomedical experimentation. Vitamin D analog synthesis has not only aided in determining the structural and stereochemical parameters of the natural metabolites, but has also helped to establish a foundation for structure-activity theories. 

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