Building up of the steroid skeleton

The total syntheses of steroids by the methods of building up the skeleton considered in this chapter were developed as early as the beginning of the thirties the workers concerned had to open up new paths which frequently led to dead ends. Consequently, in this chapter a fairly large number of ingenious but not completely successful, or even completely unsuccessful, attempts at total synthesis are described. However, they have considerable value as illustrations of new approaches to the building up of the rings and the formation of the centers of asymmetry (see, for example. Schemes 6, 7, 10, 13-15, 18, 21, 24-28, 30, 31, 49, 51, 52,55). 

This chapter includes both the earliest and the most recent methods for the total synthesis of steroids, In accordance with the methods of building up the steroid skeleton considered in it, the presentation of the material is divided into five sections. 

Syntheses of Azasteroids. Syntheses of 6-, 8-, and 9-aza-steroids have been carried out by the method of building up the steroid skeleton considered in this section (Schemes 92 and 93). 

These two compounds have in common the presence of a polycyclic steroidal skeleton, and although in both syntheses the same strategy is used to build up ring A, the synthesis of cortisone shows a greater simplicity than the synthesis of conessine. 

Total syntheses of steroids by this method of building up the skeleton have been used mainly to obtain estrogenic hormones and highly unsaturated derivatives of 19-norandrostane. These syntheses can be divided into two main groups. In the first of them, the AB and D moieties are linked initially by the formation of a C3-C14 bond, and in the second by the formation of a C12—C13 bond. Here the 11 and C12 atoms may be introduced either with the AB or with the D moiety or else, finally, be introduced into the finished tricyclic ABD intermediate. There are also variants of the synthesis in which the D ring is formed from acyclic precursors and is not introduced in finished form. In this section, syntheses of aza-, oxa-, and thia-analogs of steroid compounds are considered separately. 

Syntheses of steroids using this method of building up the skeleton have so far been studied to a very small extent and few results have been achieved methods for obtaining tetracyclic mcxiel compounds have been developed (Schemes 119 and 120). The key stage of these syntheses is the diene condensation of derivatives of 4-vinylindan with benzoquinone this leads simultaneously to the formation of ring B and the introduction of ring A as a component of the dienophile (see Chapter II, Section 3). 

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