Steroid multistep synthesis

Nowadays, many elegant syntheses of steroids, alkaloids and affiliated products are prepared from several five- or six-membered rings. Usually, the preferred steps of such syntheses correspond to the polycyclizations of educts, that contain many multiple bonds, and one or two other functional groups of further educts can often also participate [17]. However, in recent years a new type of the radical chemistry of the isocyanides has been introduced [47].This is illustrated by the one-pot synthesis of (20S)-camptothecin 25 from phenyl isocyanide 13a and 24. Such preparations of cyclopenta-fused quinolines are seldom found in tandem-domino chemistry [16], and this procedure is also closely related to the MCRs of the isocyanides. The previous multistep synthesis of 25 was accomplished by Danishefsky and Volkmann [47b], and uses a large number of linear synthetic steps with only small overall transformations towards the target. 

In pharmaceutical appHcations, the selectivity of sodium borohydride is ideally suited for conversion of high value iatermediates, such as steroids (qv), ia multistep syntheses. It is used ia the manufacture of a broad spectmm of products such as analgesics, antiarthritics, antibiotics (qv), prostaglandins (qv), and central nervous system suppressants. Typical examples of commercial aldehyde reductions are found ia the manufacture of vitamin A (29) (see Vitamins) and dihydrostreptomycia (30). An acyl azide is reduced ia the synthesis of the antibiotic chloramphenicol (31) and a carbon—carbon double bond is reduced ia an iatermediate ia the manufacture of the analgesic Talwia (32). 

Biotransformations are carried out by either whole cells (microbial, plant, or animal) or by isolated enzymes. Both methods have advantages and disadvantages. In general, multistep transformations, such as hydroxylations of steroids, or the synthesis of amino acids, riboflavin, vitamins, and alkaloids that require the presence of several enzymes and cofactors are carried out by whole cells. Simple one- or two-step transformations, on the other hand, are usually carried out by isolated enzymes. Compared to fermentations, enzymatic reactions have a number of advantages including simple instmmentation reduced side reactions, easy control, and product isolation. 

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