R. Rüegg

Retinoids, a new class of compounds with prophylactic and therapeutic activities in oncology and dermatology.

A review of recent investigations in the retinoid field is presented. Retinoic acid exerts a prophylactic and a therapeutic effect on chemically induced benign and malignant epithelial tumors in mice. In clinical studies positive therapeutic results have been obtained in patients with preneoplastic and neoplastic epithelial lesions. However, treatment with retinoic acid is limited by serious side effects (hypervitaminosis A syndrome). Therefore, the synthesis of analogs of retinoic acid (retinoids) possessing a more favorable therapeutic ratio has been initiated. Among a large series of synthesized compounds, certain aromatic analogs proved to have a particularly favorable therapeutic ratio. The structure-activity relationship of the most active retinoids is discussed including some biological data concerning prophylaxis and therapy of epithelial tumors. The total synthesis of retinoids according to various building schemes is discussed in detail. Methods for the synthesis of the cyclic end group, of the polyene chain component, and of the full retinoid skeleton are described. Metabolic studies of retinoic acid and of the most active retinoid, as well as the synthesis of some isolated metabolites are outlined. Suggestions concerning the mechanism of action of retinoids are made. Some clinical results on the treatment of acne, psoriasis and precancerous conditions are reported.

Chemistry of Vitamin E

Publisher Summary Vitamin E occurs in vegetable oils and acts as a biological antioxidant. It is distributed throughout the tissues of animals and man, and its deficiency causes a variety of syndromes in the animal organism. This chapter shows the preferred routes to specific labelings of vitamin E and has indicated the chemical research that is necessary for getting a final stereochemical insight into the tocopherol molecules. Similar investigations on related natural chromanols and ohromenols might help to elucidate their mutual biogenetic relationship. Furthermore, the reported chemical interconversions of trimethylphytylbenzoquinone into either α-tocopherol or 3,4-dehydro-α-tocopherol may indicate some biological interrelations, which might also be common to the related natural quinones, chromanols, and chromenols listed in this chapter.

Syntheses of vitamins K and related compounds with special reference to labeling.

Publisher Summary This chapter describes the structural relationships within a group of quinones widely distributed in nature and the art of building up these and similar structures in the laboratory. As many of these procedures are readily adaptable for tracer syntheses, they allow the preparation of molecules labeled at different sites and with different isotopes, thus providing useful tools for biochemical and pharmacological research. The biochemically important vitamins K, the ubiquinones, plastoquinones, and tocoquinones, comprise a series of naphtho- and benzo-quinone derivatives bearing an unsaturated side chain of several isoprene units that are linked together head to tail. The biologically important compounds of the ubiquinone and plastoquinone series are synthesized according to the methods discussed in the chapter. In addition, the conversion of quinones—for example, phylloquinone and ubiquirione-6—into the corresponding chroineriols without affecting the unsaturated side chain can be smoothly performed in boiling pyridine or with sodium hydride.

The Synthesis and Labeling of Vitamin A and Related Compounds

Publisher Summary Ever since the elucidation of the structure of vitamin A by Karrer, the synthesis of this rather unstable pentaene alcohol has been a challenge to chemists. Owing to patient and continuous efforts in many laboratories, there seems to be today an excellent picture of the possible synthetic routes to vitamin A. Although a wealth of information has been gathered on its synthesis, relatively little is known about the functions of vitamin A in the body. Knowledge on this subject broadened beginning with the advent of radioactive tracer methods. It therefore seems justified to take stock of the synthetic methods available, and to examine them as to their usefulness for the preparation of selectively labeled vitamin A compounds. These compounds will undoubtedly help the biochemists in their patient and often laborious investigations of the biological pathways that vitamin A and certain related compounds seem to control.