FARMAKOGNOSI ANALITIK

STEROIDS

What is steroids ?

Steroids form an important group of compounds based on the fundamental saturated tetracyclic hydrocarbon : 1,2-cyclopentanoperhydrophenanthrene (sterane or gonane).

 All steroids are derivatives of the hypothetical hydrocarbon sterane (I, where R = H); biogenetically, the steroids derive from squalene, which is converted into the immediate polycyclic steroid precursors lanosterol (in animals) or cycloartenol (in plants). These precursors contain 30 carbon atoms (C30). Nearly all steroids are crystalline substances that possess optical activity and dissolve more readily in organic solvents than in water.

 Steroids are widely distributed in animals and plants. The steroid group includes all the sex hormones, adrenal cortical hormones, bile acids, and sterols of vertebrates, as well as the molting hormones of insects and many other physiologically active substances of animals and plants. Among the synthetic steroids of therapeutic value are a large number of antiinflammatory agents, anabolic (growth-stimulating) agents, and oral contraceptives.

 Sterols occur in animal and Plant oils and fats, They are crystalline compound and contain an alcoholic group; they occur free or as esters of the higher fatty acids, and are isolated from the unsaponifiable portion of oils and fats. Cholesterol, 5-cholestanol-3-ol (cholestanol) and 5cholestanol-3-ol ol (coprostanol) are the animal sterols. ergosterol and stigmasterol are the plant sterols. The steroids that are obtained from animal sources are often referred to as Zoosterols and those obtained from plant sources as the phytosterols. A third group of sterols obtained from yeast and fungi are referred to as the mycosterols.

Classification of steroids

The classification of steroids is based on chemical structure and on the nature of the physiological effect or function. There are eight groups of steroids : The first group comprises the sterols, which contain a branched side chain R made up of 810 carbon atoms. Sterols are components of plant and animal lipids, and the most important sterol cholesterolparticipates in the biosynthesis of steroid hormones.

 The second groupD vitaminsis made up of unsaturated isomers of sterols (with ring B open). These isomers act to regulate calcium metabolism and the formation of the skeleton in vertebrates. The third group includes the bile alcohols and bile acids, which contain a hydroxyl or carboxylic group in the side chain (consisting of eight or five carbon atoms). These substances aid in the digestion of food in the intestines of vertebrates.

 The fourth group is that of the aglycones (genins) of steroid saponins and steroid glycoalkaloids. Typical representatives of this group are diosgenin (II, where X = O) and solasodine (II, where X = NH). Both groups of aglycones are characteristic of plants of the Liliaceae, Scrophulariaceae, and Solanaceae families, and in the form of glycosides, they have surface-active and hemolytic properties. The fifth group comprises steroid alkaloids of other types. Among them are C27 alkaloids with modified steroid skeletons (jerveratrum, ceveratrum), which stimulate the contraction of striated muscle, C21 alkaloids, which possess bactericidal and amebicidal action, and modified C21 alkaloids from the glands of amphibians (samandarine, toad poisons), which are cardiotox-ic, as well as highly toxic to the central nervous system.

 The sixth group is that of the cardiac genins, containing a side chain in the form of an unsaturated five-membered ring (C23 car-denolides) or six-membered lactone ring (C24 bufodienolides). These substances can strengthen the contraction of cardiac muscles by inhibiting the enzyme ATPase in the membrane of the heart cells. Cardenolides are found in many plants, while bufodienolides are found primarily in the venom from the cutaneous glands of toads. The seventh group comprises the steroid sex hormones and the products of the hormones conversions. These substances determine the development and operation of the sexual system in animals. They include progesterone and related C21 compounds, in which the side chain R contains two carbon atoms, as well as the male sex hormones androgenswhich contain 19 carbon atoms, and the female sex hormonesestrogenswhich contain 18 carbon atoms. A hydroxyl or carbonylic group replaces the side chain in androgens and estrogens.

 The last group includes the hormones of the adrenal cortexcorticosteroids (where R = COCH2OH)which regulate the balance of electrolytes and the metabolism of carbohydrates in vertebrates. Certain triterpene antibiotics (fusidic acid, cephalosporin P]) and other triterpenes are similar to steroids.

Biosynthesis of steroids
biosintesis kolestrol dibagi dalam tiga tahap deretan reaksi pembentukan antara lain : Pembentukan senyawa intermediate mevalonat. Diawali dengan reaksi pengabunggan 2 molekul asetilSKoA, yang dikatalis oleh enzim tiolase, dan dihasilkan asetoasetil-SKoA. Selanjutnya, asetoasetil-SKoA bereaksi dengan 1 molekul asetil-SKoA lagi membentuk senyawa OH, -CH3-SKoA (HMG-SKoA). Reaksi ini dikatalis oleh enzim HMG-SKoA sintesis. Akhirnya HMG-SKoA direduksi oleh NADPH + H+, yang dikatalis oleh enzim HMG-SKoA reduktase, dan terbentuklah mavelonat. Pembentukan kolestrol (sterol) Perubahan mevalonat menjadi senyawa sterol pertama berupa lenosterol, berlangsung melelui pembentukan dua senyawa intermediate, berturut-turut berupa senyawa unit isoprenoid dan skualen. Kolestrol diturunkan dari lenosterol melalui pembentukan senyawa intermediate berupa senyawa 14-desmetillano-sterol, zimosterol, 7, 24 kolestadienol, desmosterol dan pada akhirnya terbentuklah kolestrol.

 Pembentukan kolestrol dari skualin Pada tahap terakhir proses biosintesis kolestrol, skualin bereaksi dengan oksigen menghasilkan skualin-2,3-epoksida. Reaksi ini dikatalis oleh skualin monooksigenase. Selanjutnya skualin-2.3-epoksida mengalami proses suklisasi, yang dikatalis oleh enzim skualin epoksida lanosterol-siklase, menghasilkan lenosterol. [erubahan linosterol menjadi kolestrol berlangsung dengan pelepasan tiga gugus metal (dua atom karbon nomor empat dan satu dari atom karbon nomor 14), reduksi ikatan rangkap dari rantai samping kolestrol, dan perpindahan ikatan rangkap dari posisi-8,9 ke posisi-5,6 dalam cincin B. perubahan linosterol dapat berlangsung melalui salah satu dari dua jalur reaksi, yaitu melalui pembentukan desmoserol atau melalui 7dehidroksikolestrol.

The biosynthesis of steroids is an operation more characteristic of higher vertebrates. Insects do not produce steroids and instead obtain these compounds from their food. However, the critical function of molting is controlled by a special type of C27 sterol known as ecdysone. Derivatives of progesterone serve as a means of chemical protection for a number of species of insects. Sexual reproduction in certain lower fungi (Achlya) is also induced by steroids. Steroids may participate in the morphogenesis of vascular plants. Inhibitors of the biosynthesis of steroids prevent the reproduction of certain fungi and the flowering of higher plants.

Nomenclature of steroids
When some of the carbon atoms are missing, the numbering of the remainder remains unchanged. Solid lines (preferably thickened) denote groups above the plane of the nucleus (- configuration), and dotted or broken lines denote groups below the plane (-configuration), if the configuration of the substituent is unknown, its bond to the nucleus is drawn as a wavy line and this is indicated by in the name. Wherever possible, the name of the steroid should specify stereochemical configuration. Trivial names have been retained for steroid hormones and closely related compounds. Because of the introduction of these rules of nomenclature, some names used in the earlier literature are now discarded, e.g. coprostane is now named as 5-cholestane ; isocompounds; (i-compounds) are now called cyclo-compounds.

Cholesterol

This is the sterol of' the higher animals, occurring free or as fatty esters in all animals in the brain and spinal cord. Cholesterol was first isolated from human gallstone. The main sources of cholesterol are the fishliver oils. Cholesterol is a white crystalline solid, which is optically active.

 Colour Reactions of Cholesterol (i) The Salkowaski reaction (1908) : (ii) When concentrated sulphuric acid is added to cholesterol in chloroform, a red colour is produced in the chloroform layer. (ii) The Liebermann- Burchard reaction (1885, 1890): A greenish colour is developed when the solution of cholesterol in chloroform is treated with concentrated sulphuric acid and acetic anhydride. When an ethanolic solution of cholesterol is treated with an ethanolic solution of digitonin, a large white precipitate of cholesterol digitonide is formed, a complex containing one molecule of cholesterol and one of digitonin, from which component may be recovered by dissolving the complex in pyridine.

Stigmasterol