ChemInform Abstract: A Concise Route to 19-Nor-10-azasteroids, a New Class of Steroid 5α-Reductase Inhibitors. Part 3. Synthesis of (+)-19-Nor-10-azatestosterone and (+)-17β-(Acetyloxy)-(5β)-10-azaestr-1-en-3-one.

✍ Scribed by A. GUARNA; E. G. OCCHIATO; F. MACHETTI; D. SCARPI

• Publisher: John Wiley and Sons
• Year: 2010
• Weight: 43 KB
• Volume: 29
• Category: Article
• ISSN: 0931-7597
• DOI: 10.1002/chin.199841196

✦ Synopsis

A Concise Route to 19-Nor-10-azasteroids, a New Class of Steroid 5α-Reductase Inhibitors.

Part 3. Synthesis of (+)-19-Nor-10azatestosterone and (+)-17β-(Acetyloxy)-(5β)-10-azaestr-1-en-3-one.

-The title compounds are of interest, since 5α-reductase inhibitors (by reducing the level of dihydrotestosterone in the target tissues) could be used as drugs for the pharmacological treatment of androgen-dependent disorders. A new route for the synthesis of 19-nor-10-azasteroids (IX) and (XII) is presented, based on a tandem N-(acyloxy)iminium-Michael addition reaction of (VII) with an appropriate siloxydiene to construct the A ring. This provides azasteroidal compounds in only six steps with overall yields of 21-31%, which is considerably shorter and more efficient than other known methods. Another advantage is the different substitution pattern of the A ring by using suitably substituted siloxy-1,3-butadienes. The starting acid (I), maintaining the C and D ring already, is obtained from microbial degradation of sterols present in the soya bean. -(GUARNA, A.