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

A gram-scale synthesis of [3,4-13C2,1a,7-2H2]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 [1,2-13C2]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, [3,4-13C2,1a,7-2H2]-11-dehydrocorticosterone, [3,4-13C2,1a,7-2H2]cortisol, and [3,4-13C2,1a,7-2H2]corticosterone were also prepared. Copyright (C) 2011 John Wiley & Sons, Ltd.