Bile Acids

Cholesterol Bile

The bile acids are C24 steroidal acids that occur in salt form in bile, secreted into the gut to emulsify fats and encourage digestion. They act as detergents by virtue of their relatively non-polar steroid nucleus and the polar side-chain, which contains a carboxylic acid group, that is typically bound via an amide linkage to glycine or taurine. Thus, for example, cholic acid Figure 5.108 is found as sodium glycocholate and sodium tauro-cholate. Metabolism to bile acids is also the principal...

Mevastatin and other Statins

Mevastatin Hydrolysed Form

Mevastatin formerly compactin Figure 3.83 is produced by cultures of Penicillium citrinum and P. brevicompactum, and was shown to be a reversible competitive inhibitor of HMG-CoA reductase, dramatically lowering sterol biosynthesis in mammalian cell cultures and animals, and reducing total and low density lipoprotein cholesterol levels see page 236 . Mevastatin in its ring-opened form Figure 3.84 mimics the half-reduced substrate mevaldate hemithioacetal during the two-stage reduction of...

Phytosterols

The major sterol found in mammals is the C27 compound cholesterol, which acts as a precursor for other steroid structures such as sex hormones and corticosteroids. The main sterols in plants, fungi, and algae are characterized by extra one-carbon or two-carbon substituents on the side-chain, attached at C-24. These substituent carbons are numbered 241 and 242 Figure 5.77 some older publications may use 28 and 29. The widespread plant sterols campesterol and sitosterol Figure 5.100 are...

Tetraterpenes C40

Tetraterpene

The tetraterpenes are represented by only one group of compounds, the carotenoids, though several hundred natural structural variants are known. These compounds play a role in photosynthesis, but they are also found in non-photosynthetic plant tissues, in fungi and bacteria. Formation of the tetraterpene skeleton, e.g. phytoene, involves tail-to-tail coupling of two molecules of ger-anylgeranyl diphosphate GGPP in a sequence essentially analogous to that seen for squalene and triterpenes Figure...

Semi Synthesis of Corticosteroids

Synthesis Beclometasone Propionate

The medicinal use of corticosteroids was stimulated by reports of the dramatic effects of cortisone on patients suffering from rheumatoid arthritis in the late 1940s and early 1950s. The cortisone employed was isolated from the adrenal glands of cattle, and later was produced semi-synthetically by a laborious process from deoxycholic acid see page 260 isolated from ox bile and necessitating over 30 chemical steps. Increased demand for cortisone and hydrocortisone cortisol it had been shown that...

Forskolin

In a screening programme of Indian medicinal plants, extracts from the roots of Coleus forskohlii Labiatae Lamiaceae were discovered to lower blood pressure and have cardioactive properties. This led to the isolation of the diterpene forskolin coleonol Figure 5.51 as the active principle in yields of about 0.1 . Forskolin has been shown to exert its effects by direct stimulation of adenylate cyclase, and has become a valuable pharmacological tool in the study of this enzyme and its functions....