Progesterone from Mexican Yams Key Words

Home , Marker degradation, Sarsasapogenin

R. E. MARKER, T. TSUKAMOTO, D. L. TURNER (PENNSYLVANIA STATE COLLEGE, USA Category AND KANAZAWA UNIVERSITY, JAPAN) Chemistry in Sterols. C. Diosgenin Medicine and J. Am. Chem. Soc. 1940, 62, 2525–2532, DOI: 10.1021/ja01866a072. Biology

Progesterone from Mexican Yams Key words

steroids

degradation O H H progesterones Ac2O O O H H H 200 °C H OAc H H H H HO AcO diosgenin A

O O O 17 CrO3, AcOH NaOH, EtOH H O H 16 oxidative cleavage saponification of double bond and H H AcO H H elimination of AcO alcohol HO 5,16-pregnadien-3β-ol-20-one (B)

O O

Pd, H2 Al(Oi-Pr)3, Me2CO H H Oppenauer oxidation H H H H HO O C progesterone

Significance: Steroids are important, bioactive Comment: Building on their previous work on the molecules and many important drugs such as im- structural elucidation and degradation of the side munosuppressants and contraceptives belong to chain of sarsasapogenin, Marker and co-workers the steroid class. In the 1930s, the tremendous po- showed that the side chain of diosgenin (highlight- tential of steroids had already been realized, but re- ed in red) could be degraded in a similar fashion. search on steroids was significantly hampered by The first step in the Marker degradation involves limited supply of steroids from natural and synthet- treatment of diosgenin with Ac2O at high tempera- ic sources, with progesterone being more expen- tures to give dihydrofuran A. The double bond in This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. sive than gold. This changed when Marker and co- the dihydrofuran is then cleaved using CrO3, fol- workers described a series of transformations that lowed by saponification and elimination of the re- converted diosgenin into progesterone and addi- sulting alcohol, yielding B. Selective reduction of tionally identified Mexican yams as an abundant the C16,17 double bond yielded C, which could be source of diosgenin. By using the process, now oxidized to progesterone via an Oppenauer oxida- known as the Marker degradation, Marker and co- tion. It is worth noting that Marker also developed workers synthesized the largest single batch of pro- an approach to convert B into testosterone. gesterone at the time, laying the foundation for the steroid industry in Mexico and future research.

SYNFACTS Contributors: Dirk Trauner, Alexander J. E. Novak Synfacts 0122020, 16(12), 1485 Published online: 17.11.20201861-19581861-194X

DOI: 10.1055/s-0040-1719560; Reg-No.: T13420SF Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stutgart