Vitamin A derivatives

The stmcture of vitamin A [11103-57-4] and some of the important derivatives are shown in Figure 1. The parent stmcture is aH-Zra/ j -retinol [68-26-8] and its lUPAC name is (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-l-cyclohexen-l-yl)-2,4,6,8-nonatetraen-l-ol (1). The numbering system for vitamin A derivatives parallels the system used for the carotenoids. In older Hterature, vitamin A compounds are named as derivatives of trimethyl cyclohexene and the side chain is named as a substituent. For retinoic acid derivatives, the carboxyl group is denoted as C-1 and the trimethyl cyclohexane ring as a substituent on C-9. The stmctures of vitamin A and -carotene were elucidated by Karrer in 1930 and several derivatives of the vitamin were prepared by this group (5,6). In 1935, Wald isolated a substance found in the visual pigments of the eye and was able to show that this material was identical with Karrer s retinaldehyde [116-31-4] (5) (7). 

Currently, 13-cis-retinoic acid is the most studied chemopreventive agent that decreases the incidence of second primary tumors in patients with head-and-neck cancer, reverses premalignant lesions, and reduces appearance of nonmelanoma skin cancer in patients with xeroderma pigmentosum. Unfortunately, this vitamin A derivative has a significant clinical toxicity, which limits its utility in a practice setting. 

We see some similarities between the major life processes in plants (growth and differentiation) and the major life processes in animals and humans (proliferation and differentiation). We expect in future to relate this concept to animal production and to human health, to be able to cross the bridge from soil to plant to animal and finally human health. For example, the development in medicine of differentiation therapy in which vitamin A-derivates are used to treat human cancer cells in vitro (De Luca el al., 1995). Cancer is defined by too much uncontrolled growth of cells without enough differentiation. Using treatment with vitamin A-derivatives - a product of differentiation processes in the plant - undifferentiated cancer cells change into differentiated more healthy ones. 

In that way, one of the principal approaches to the preparation of vitamin A derivatives consists of a selection of starting and/or intermediate structures which cannot be rearranged. In contrast, the object of another approach is to search the conditions of the reverse transformation, i.e. a rearrangement of retro-structures to the desirable ionylidene systems. Most frequently, basic reagents (e.g. NaOH, KOH, AcOK, pyridine, AlkONa etc.) are used for this purpose but an application of acid reagents is also known146. 

Kistiakowsky-Fishtine equation puys chem An equation to calculate latent heats of vaporization of pure compounds useful when vapor pressure and critical data are not available., kis-te-a k6f-ske fa shtTn i,kwa-zhan kitol oRG CHEM C40H60O2 One of the provitamins of vitamin A derived from whale liver oil crystallizes from methanol solution. ke,tol ... 

A vitamin A derivative, ll-cw-retinal, is central to the visual process in humans. It is derived from all-trani-retinol by converting the terminal hydroxyl group to an... 

Chemical Class-. Retinoid prodrug vitamin A derivative... 

Tanaka et al. reported a synthesis of vitamin A derivatives from C15 phosphonates [85]. Vitamin A acetate was prepared in 92% yield by reaction of the C15 phosphonate with 2-methyl-4-acetoxy-2-butenal, Fig. (47). 

Science has made remarkable gains in the area of skin care in the past 20 years. The development of vitamin A derivatives brought clinically proven reductions in wrinkles. Fruit acids. Ceramide compounds and a library of plant derivatives diminished the impacts of aging. 

Pd-catalysed decarboxylation-elimination offers a useful method for regioselective generation of conjugated dienes. The polyene system of vitamin A derivative 381 is prepared from the /f-acetoxycarboxylic acid 379 by decarboxypalldation, as shown by 380 [172],... 

The UV radiation causes premature skin aging. This photo-aging is characterized by wrinkles, mottled pigmentation, dry and rough skin, and loss of skin tone. Use of topical vitamin A derivatives like tretinoin can improve photo-aged skin mainly by changing epidermal differentiation.52 However, skin dryness does not improve and even worsens with retinoid therapy, as well known from its systemic and topical use in several diseases in clinical dermatology. 

Impairment of the retinoid signal transduction pathways occurs as a result of prolonged UV exposure. Down regulation of nuclear receptors for Vitamin A occurs,269 resulting in a functional deficiency of Vitamin A. Application of Vitamin A derivatives would appear to be an obvious treatment modality. Topical application of Vitamin A does increase the HA in the epidermal layer, increasing the thickness of the HA meshwork after prolonged treatment.270 Vitamin A thus enhances repair, as can be demonstrated in photo-aged hairless mouse model.271 The decline in GAG, and in particular HA deposition that occurs with UVB irradiation, can be entirely prevented by retinoic acid treatment. 

Vitamin A (Retinol), Retinoids (Vitamin A Derivatives), and Carotenoids. 380... 

Vitamins are essential nutrients, which must be supplied exogenously. They are organic compounds with indispensable biological activities as coenzymes in a multitude of cellular metabolic processes. Vitamin A, retinoids (vitamin A-derivatives), carotenoids, vitamin D, vitamin E, and vitamin K are fat-soluble, vitamin C and vitamins of the B-complex are water-soluble. This is of importance for gastrointestinal absorption in oral supplementation as well as the transdermal penetration for topical applications. 

VITAMIN A (RETINOL), RETINOIDS (VITAMIN A DERIVATIVES), AND CAROTENOIDS... 

The first synthesis of a vitamin A derivative was described by H. H. Inhoffen, D. A. von Dorp and J. F. Arens in 1944 for the vitamin A acid (retinoic acid 5)2). The first syntheses 3) of vitamin A (2), discovered independently of one another, became known in 1947, and were followed as early as 1948 by an industrial... 

Figure 6.6 Biosynthesis of various vitamin A derivatives from /3-carotene and their role in human physiology.

Vitamin A (retinols) plays a role in epithelial function and the retinoic acid derivative, acitretin (Neotigason, orally), inhibits psoriatic hyperkeratosis over 4-6 weeks. Acitretin should be used in courses (6-9 months) with intervals (3-4 months). It is teratogenic, like the other vitamin A derivatives. Rigorous precautions for use in women of childbearing potential are laid down by the manufacturer and must be followed, including contraception for 2 years after cessation, because the drug is stored in the liver and in fat and released over many months. The plasma t) is 3 months. It can cause other serious toxicity (see Vitamin A, p. 739). Tazarotene, a topical retinoid, is of some benefit in mild psoriasis, but is irritant. 

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