Preparation of multiply deuterium-labeled cortisol.
Cortisol labeled with four deuterium atoms at chemically stable sites ([9,11,12,12-(2)H4]cortisol, cortisol-d4) was prepared by hydrogen-deuterium exchange and reductive deuteration reactions. After protecting the C-17 dihydroxyacetone side chain of cortisone (cortisone-BMD), hydrogen-deuterium exchange was carried out with 6.5% NaOD in MeOD, which was followed by protection of the C-3 carbonyl as the semicarbazone. Subsequent reductive deuteration at C-11 with NaBD4 followed by removal of exchangeable deuterium under the same exchange-reaction conditions in a medium of 6.5% NaOH in MeOH and deprotection afforded the desired cortisol-d4 with high isotopic content (d3, 21.2%; d4, 78.1%; d5, 0.74%). The method was applied to the synthesis of cortisol labeled with nine deuterium atoms [( 1,1,9,11,12,12,19,19,19-(2)H9]cortisol, cortisol-d9) starting from [1,1,19,19,19-(2)H5]cortisone (cortisone-d5).
Shibasaki
H
H
Department of Medicinal Chemistry and Clinical Pharmacy, Tokyo College of Pharmacy, Japan.
Furuta
T
T
Kasuya
Y
Y
D003348:Cortisone / Q000737:chemistry; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D006854:Hydrocortisone / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*
D003903:Deuterium; D003348:Cortisone; D006854:Hydrocortisone