Taxus brevifolia and Taxol Paclitaxel

Taxol Production

A note on nomenclature the name taxol was given to a diterpene ester with anticancer properties when it was first isolated in 1971 from Taxus brevifolia. When the compound was subsequently exploited commercially as a drug, Taxol was registered as a trademark. Accordingly, the generic name paclitaxel has been assigned to the compound. The literature now contains an unhappy mixture of the two names, though the original name taxol is most often employed. The anticancer drug taxol Figure 5.43 is...

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...

Unsaturated Fatty Acids

Animal fats contain a high proportion of glyc-erides of saturated fatty acids and tend to be solids, whilst those from plants and fish contain predominantly unsaturated fatty acid esters and tend to be liquids. Some of the common naturally occurring unsaturated fatty acids are also included in Table 3.1. A convenient shorthand representation for fatty acids indicating chain length with number, position and stereochemistry of double bonds is also presented in Table 3.1. A less systematic...

Semi Synthesis of Corticosteroids

Synthesis Betamethasone

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....

Oxidative Cleavage of Aromatic Rings

Perhaps the most drastic modification which can happen to an aromatic ring is ring cleavage brought about by oxidative enzymes called dioxygenases see page 27 . These enzymes typically use catechol 1,2-dihydroxy or quinol 1,4-dihydroxy substrates, require molecular oxygen and Fe2 cofactors, and incorporate both the oxygen atoms into the ring-cleaved product. In the case of catechols, cleavage may be between or adjacent to the two hydroxyls, giving products containing aldehyde and or carboxylic...