Modified steroid skeleton

Terms used to describe modified steroid skeletons include nor (shortening of a side chain or contraction of a ring), homo (expansion of a ring), cyclo (formation of an additional ring), seco (fission of a ring), and abeo (migration of a bond). 

The generxc witha steroids which has been proposed does not seem to have gained much popularity. For compounds with a modified carboxylic skeleton and or side chain, only CA names are being used, along with the trivial names. 

In their total synthesis of 6-methyl-5-androstene-3,l 1,17-trione 3-ethylene acetal, which is a building block for 6a-methylprednisolone, Daniewski and co-workers used a modified Wichterle reaction to install the A-ring of the natural product/ A racemic mixture of 56 was used in a reductive alkylation with Wichterle s reagent to afford the product 57 as a mixture that could be separated by chromatography. Upon treatment of each diastereomer of 57 with formic acid and perchloric acid to induce cyclization, it was observed that both diastereomers resulted in the same enantiopure product 58. This preferred conformation of the steroidal skeleton was confirmed by comparison to an authentic sample of the product that can be obtained directly from natural cortisone. 

Total synthesis is in the mainstream of modern tendencies of the development of steroid chemistry, the main characteristic of which is the synthesis of modified steroid compounds. The methods of total synthesis open up greater possibilities for the modification of molecules than synthesis from natural compounds with the skeleton already formed. It is obvious that the further we depart from natural steroids in the modification process, the better are the prospects for the use of total synthesis. Consequently, at the present time it is possible to outline the field of modification within which total synthesis is the most suitable method, if not the only possible one. This field includes, for example, 18-homo-steroids and the highly unsaturated -steroids. However, here... 

Cholesterol was isolated m the eighteenth century but its structure is so complex that Its correct constitution was not determined until 1932 and its stereochemistry not verified until 1955 Steroids are characterized by the tetracyclic ring system shown m Figure 26 9a As shown m Figure 26 9b cholesterol contains this tetracyclic skeleton modified to include an alcohol function at C 3 a double bond at C 5 methyl groups at C 10 and C 13 and a C Hn side chain at C 17 Isoprene units may be discerned m var lous portions of the cholesterol molecule but the overall correspondence with the iso prene rule is far from perfect Indeed cholesterol has only 27 carbon atoms three too few for It to be classed as a tnterpene... 

Semisystematic names. Examples of semisystematic parents are corynoxan and labdane. DNP makes widespread use of semisystematic names for terpenoids and steroids (where skeletons such as labdane have not been used in CAS nomenclature since 8C1). lUPAC gives tables of recognised semisystematic parent skeletons and directions for introducing new ones, but in view of the discovery of ever more structurally complex types of natural products, most authors have avoided this route. Semisystematic parents can be modified by operators such as nor-, abeo. 

Fig. 36.15. Proposed biosynthetic scheme for the origin of steroid alkaloids with unaltered C27 skeletons (modified from Gross et al., 1985).

The basic cholesterol skeleton can also be modified by the incorporation of a nitrogen heteroatom as in the steroidal alkaloids. Two examples are abutilosides A and B (66 and 67) isolated from S. abutiloides [68-70], which are closely related to the open-chain steroidal glycosides abutilosides D-G (47-50) [45] discussed above. Glycosteroidalkaloids such as these are particularly abiuidant in the Solanum (Solanaceae) [68-70], Lycopersicon (Solanaceae) [71-73], and Fritillaria (Liliaceae) [74—76]. 

Almost all types of oxygen functionalities are present in this class of steroidal lactones, and the characteristic IR spectral bands for various functionalities appear in the spectra. The characteristic enone and a,) -unsaturated Mactone moieties of withanohdes show absorptions at or near the 1,660 and 1,710 cm, respectively. An IR absorption at 1,778 cm is due to carbonyl stretching vibrations in five-membered lactone ring, found in all physalins and other classes of withanolides with modified skeleton [34-36]. 

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