Steroid side chain problem

Stereocontrolled construction of the natural configuration 327 at C-20 in steroid side-chains is an important problem in steroid synthesis. In addition, preparation of the... 

When using the 5,6-dibromide for protection during the ozonolysis of a steroid side-chain olefin, it was found [46] that reductive work up of the ozonide led to removal of the protecting group. This problem was solved by protection of the olefin by hydrochlorination. The olefin could subsequently be regenerated by treatment with base. Meystre [47, 48] used this method of protection in a sequence which required bromina-tion-dehydrobromination at another part of the molecule. 

The major problem in such conversions is the degradation of the branched carbon side-chain on C-17 which is present in all abundant steroids and lacking in all steroid hormones. The most important starting material used in industry today is diosgenin from the Mexican dioscorea plant. It is degraded by the method of Marker to 16-dehydropregnenolone in 45% total yield. This compound is a key substance in the production of several hormones with anabolic, catabolic, and sexual effects. 

The cheapest of all sterols, however, is cholesterol, followed by ]3-sitos-terol. Both steroids have saturated side chains. Their chemical degradation is complicated and expensive and has no commercial value today. Biotechnology solved this problem. Fermentation with Mycobacterium phlei, Nocardia, or Arthrobacter in the presence of various inhibitors (e.g., nickel sulfate, cobalt chloride, 8-hydroxyquinoline) gives androstadiene-dione. From that point one can get anywhere in steroids by simple chemical modification. Only the degrada-... 

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