Synthesis of deuterium-labeled tetrahydrocortisol and tetrahydrocortisone for study of cortisol metabolism in humans.
A method is described for the preparation of multi-labeled tetrahydrocortisol (3alpha,11beta,17alpha,21-tetrahydroxy-5beta-[1, 2,3,4,5-2H5]pregnan-20-one, THF-d5), allo-tetrahydrocortisol (3alpha,11beta,17alpha,21-tetrahydroxy-5alpha-[1 ,2,3,4,5-2H5]pregnan-20-one, allo-THF-d5), and tetrahydrocortisone (3alpha,17alpha,21-trihydroxy-5beta-[1,2,3,4,5-2H5]pre gnane-11,20-dione, THE-d5) containing five non-exchangeable deuterium atoms in the steroid ring A. Reductive deuteration at C-1, C-2, C-3, C-4, and C-5 of prednisolone or prednisone was performed in CH3COOD with rhodium (5%) on alumina under the deuterium atmosphere. The isotopic purities of the labeled compounds as [2H5]-form were estimated to be 86.17 atom%D for THF-d5, 74.46 atom%D for allo-THF-d5 and 81.90 atom%D for THE-d5, based on the ion intensities in the region of the molecular ion of methoxime-trimethylsilyl (MO-TMS) derivatives measured by GC-MS.
Furuta
T
T
Department of Medicinal Chemistry and Clinical Pharmacy, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Namekawa
T
T
Shibasaki
H
H
Kasuya
Y
Y
D002853:Chromatography, Liquid; D003903:Deuterium; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013760:Tetrahydrocortisol / Q000378:metabolism*; D013761:Tetrahydrocortisone / Q000378:metabolism*
D013761:Tetrahydrocortisone; D013760:Tetrahydrocortisol; D003903:Deuterium; D006854:Hydrocortisone