A gram-scale synthesis of [3,4-13C2,1α,7-2H2]cortisone

✍ Scribed by Zizhong Li; Peter Heffner; Yumin Gong

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: French
• Weight: 497 KB
• Volume: 54
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1938

✦ Synopsis

A gram‐scale synthesis of [3,4‐^13^C~2~,1__α__,7‐^2^H~2~]cortisone from prednisone was developed. The deuterium atom at the C‐1 position was introduced through a regioselective and stereoselective deuteration of the 1,2‐double bond of the 1,4‐diene‐3‐one using Wilkinson's catalyst. After the oxidative cleavage of the A‐ring, two carbon‐13 atoms were introduced via acetylation of an A‐ring enol lactone with [1,2‐^13^C~2~]acetyl chloride. The steroidal A‐ring was then reconstructed to incorporate the carbon‐13 atoms into the C‐3 and C‐4 positions. The deuterium atom at C‐7 was introduced through a regioselective deuteration of the 6,7‐double bond of a 4,6‐diene‐3‐one intermediate using palladium on strontium carbonate. The M + 4 stable isotope labeled cortisone was thus prepared in ca. 4% overall yield. In addition, [3,4‐^13^C~2~,1__α__,7‐^2^H~2~]‐11‐dehydrocorticosterone, [3,4‐^13^C~2~,1__α__,7‐^2^H~2~]cortisol, and [3,4‐^13^C~2~,1__α__,7‐^2^H~2~]corticosterone were also prepared. Copyright © 2011 John Wiley & Sons, Ltd.