Gomez-Sanchez C E, Kirk D N, Farrant R D, Milewich L
J Steroid Biochem. 1985 Jan;22(1):141-6. doi: 10.1016/0022-4731(85)90154-2.
The isolation of 18-hydroxycortisol from the urine of patients with primary aldosteronism was recently described and no synthetic procedure was available for its preparation. The C-13 angular methyl group of prednisolone-17 alpha,21-acetonide-11 beta-nitrite was functionalized by photolysis in the presence of oxygen to give the product 18-hydroxy-prednisolone-17 alpha,21-acetonide-18-nitrate. The 18-nitrate was reduced with zinc and ammonium acetate to the corresponding 18-hydroxy compound, 18-hydroxy-prednisolone-17 alpha,21-acetonide. Homogeneous hydrogenation with Tris(triphenyl-phosphine)rhodium (I) chloride as catalyst resulted in the formation of 18-hydroxy-cortisol-17 alpha,21-acetonide. Acid hydrolysis of the latter compound gave 18-hydroxycortisol. Oxidation of 18-hydroxycortisol-17 alpha,21-acetonide with pyridinium dichromate followed by acid hydrolysis gave 18-hydroxycortisone. The 18-hydroxylated steroids exist as the 18,21-hemiacetals. Catalytic reduction with tritium gas with Tris(triphenyl-phosphine)rhodium (I) chloride of 18-hydroxyprednisolone-17 alpha,21-acetonide and acid hydrolysis gave [1,2(3)H]18-hydroxycortisol.
最近报道了从原发性醛固酮增多症患者尿液中分离出18 - 羟基皮质醇，且尚无其合成方法。在氧气存在下，通过光解使泼尼松龙 - 17α,21 - 缩丙酮 - 11β - 亚硝酸盐的C - 13角甲基官能化，得到产物18 - 羟基 - 泼尼松龙 - 17α,21 - 缩丙酮 - 18 - 硝酸盐。用锌和醋酸铵将18 - 硝酸盐还原为相应的18 - 羟基化合物，即18 - 羟基 - 泼尼松龙 - 17α,21 - 缩丙酮。以三（三苯基膦）氯化铑（I）为催化剂进行均相氢化反应，生成18 - 羟基 - 皮质醇 - 17α,21 - 缩丙酮。后者经酸水解得到18 - 羟基皮质醇。用重铬酸吡啶鎓氧化18 - 羟基 - 皮质醇 - 17α,21 - 缩丙酮，随后进行酸水解，得到18 - 羟基可的松。18 - 羟基化甾体以18,21 - 半缩醛形式存在。用氚气在三（三苯基膦）氯化铑（I）催化下还原18 - 羟基泼尼松龙 - 17α,21 - 缩丙酮并进行酸水解，得到[1,2(3)H]18 - 羟基皮质醇。
