Biotransformation of lipids Although representatives of all of the classes of sterols and steroids are essential to steroids have humans, the biological (pharmacological)activities of the C18, C19 and cz steroids make pharmac vaa these potentially very useful as therapeutic agents. It has long been realised that variations on the structures of naturally occurring steroids lead to products with greatly modified biological activities. Thus we can visualise the situation in which steroids may be modified to produce substances which have enhanced or reduced activities. This has far reaching implications in the healthcare sector. For example, natural and modified corticosteroids have applications as anti-inflammatory agents and may be used where the immune response needs to be moderated. Similarly the ability of C1g and Ci8 steroids to modulate reproductive capabilities makes them useful as fertility agents and as ∏ Which of the groups of compounds shown in Figure 9.1 is(are)likely to be of greatest commercial (and social) value? steroids are of Again, the answer should be fairly obvious. The potential therapeutic value of the great steroid hormones makes these of tremendous commercial value. the commercial commercial valu market for these is of the order of hundreds of millions of dollars per year. There is no comparable market for sterols and bile salts. We are faced with the interesting situation, herefore, that sterols are relatively abundant in natural sources but of relatively low commercial value, whilst steroids occur naturally at very low concentrations but are of great commercial value. Although there are tremendous variations amongst different products, steroids with desirable properties command market prices that are(ten toone thousand fold) greater than their sterol counterparts Bearing in mind the relative abundance of sterols and steroids and their chemical structures, which of the following strategies for producing steroids is most likely to be commercially successful? 1)Extraction from animals. 2) Total chemical synthesis 3)Partial chemical synthesis starting from a natural product. 4) Total biosynthesis 5)Enzymatic transformation of natural products Below we have considered each of these strategies in turn. 1)Although animals produce steroids, the low concentrations of these compounds does not make these commercially (nor ethically)attractive sources of these substances. Furthermore, they could only serve as sources of naturally occurring steroids. Thus we would not have selected this option y The steroid ring structure is complex and contains many chiral carbons(for example at positions 5, 8, 9, 10, 13, 14 and 17) thus many optical isomers are possible. (The actual number of optical isomers is given by 2 where n =the number of chiral carbons). From your knowledge of biochemistry you should have realised that only ne of these optical isomers is likely to be biologically active. Synthesis of such a complex chemical structure to produce a single isomeric form is extremely difficult, especially when it is realised that many chemical reactions lead to the formation of racemic mixtures. Thus, for complete chemical synthesis, we must anticipate thatBiotransformation of lipids 297 Although representatives of all of the classes of sterols and steroids are essential to humans, the biological (pharmacological) activities of the CW, CI~ and Cn steroids make these potentidy very usef~l as therapeutic agents. It has long been realid that variations on the structures of naturally occurring steroids lead to products with greatly modified biological activities. Thus we can visualise the situation in which steroids may be modified to produce substances which have enhanced or reduced activities. This has far reaching implications in the healthcare sector. For example, natural and modified corticosteroids have applications as anti-inflammatory agents and may be used where the immune response needs to be moderated. Similarly the ability of CM and CI~ steroids to modulate reproductive capabilities makes them useful as fertility agents and as contraceptives. Which of the groups of compounds shown in Figure 9.1 is (are) likely to be of n greatest commeraal (and social) value? Again, the answer should be fairly obvious. The potential therapeutic value of the steroid hormones makes these of tremendous commercial value. The commercial market for these is of the order of hundreds of millions of dollars per year. There! is no comparable market for sterols and bile salts. We are faced with the interesting situation, therefore, that sterols are relatively abundant in natural sources but of relatively low commeraal value, whilst steroids occur naturally at very low concentrations but are of great commeraal value. Although there are tremendous variations amongst different products, steroids with desirable properties command market prices that are (ten to one thousand fold) greater than their sterol counterparts. Sbdds have @mamutical value steroids are of gFt commeraal ValUe Bearing in mind the relative abundance of sterols and steroids and their chemical structures, which of the following strategies for producing steroids is most likely to be commercially successful? n 1) Extraction from animals. 2) Total chemical synthesis. 3) Partial chemical synthesis starting from a natural product. 4) Total biosynthesis. 5) Enzymatic transformation of natural products. Below we have considered each of these strategies in turn. 1) Although animals produce steroids, the low concentrations of these compounds does not make these commercially (nor ethically) attractive sources of these substances. Furthermore, they could only serve as sources of naturally occurring steroids. Thus we would not have selected this option. The steroid ring structure is complex and contains many chiral carbons (for example at positions 5,8,9,10,13,14 and 17) thus many optical isomers are possible. (The actual number of optical isomers is given by 2" where n = the number of chiral carbons). From your knowledge of biochemistry you should have realised that only one of these optical isomers is likely to be biologically active. Synthesis of such a complex chemical structure to produce a single isomeric form is extremely difficult, especially when it is realised that many chemical reactions lead to the formation of racemic mixtures. Thus, for complete chemical synthesis, we must anticipate that