Recent Advances in the Total Synthesis of Steroids

Abstract

In the total synthesis of steroids on the industrial scale, three factors are important: stereoselectivity of the reactions used, resolution of' racenzic intermediates at the earliest possible slage, and convergence ofthe synthesis. Theoretical advances and wider practical experience in the chemistry 0fpoI)xyclic compounds have recently led to the development 01 ihe first syntheses which are suitable for tlie industrial production of steroid hormones.Arigew. Chem. intermit. Edit. / VoI. 4(1965) Nu. 3

Synthesis of D-norisomorphinans ((±)-[14α]-D-normorphinans)

“…7). The syn 1,3-diaxial interactions between the large aminomethyl group and the axial hydrogens at C(l) and C(3) are intensified by the ring B unsaturation.…”

Steroids

“…Appendage of the A-ring functionality by alkylation produced intermediate (273). Compound (273) was used as a common intermediate for the synthesis of 19-norsteroids, estrogens, and corticosteroids (230).…”

Bc → BCD → Abcd

“…Later, Velluz and his group [5][6][7][8][9][10][11] at Roussel-UCLAF using the transbenzohydrindanes 8 and 9 as the starting material, accomplished the first successful stereospecific total synthesis of steroids on an industrial scale. By 1960, they were able to complete the total synthesis of a host of optically active steroids including 19-nortestosterone (21), cortisone (28, R = H), and estradiol (30).…”

“…One of the major contributing factors in their success stemmed from their ability to resolve the racemates in 201 the earliest possible stage in the synthetic scheme. Another significant modification was the extensive use of the concept of convergence of synthetic schemes [5,6]. In this approach two fragments of the future steroids containing the latent functional groups are formed initially.…”