Institute of Organic and Biomolecular Chemistry, Georg-August University of Göttingen, Tammannstr. 2, 37077, Göttingen, Germany.
Chemistry. 2020 Dec 1;26(67):15733-15737. doi: 10.1002/chem.202004154. Epub 2020 Nov 19.
Aldosterone 1 is a mineralocorticoid, it has great influence on the blood pressure and its glucuronide is an important marker for the detection of several diseases. Here, we describe the chemical synthesis of different aldosterone-18- and 20-glucuronides. Reaction of trimethylsilyl 2,3,4-tri- acetyl-1-β-glucuronic acid methyl ester 5 b and aldosterone diacetate 11 in the presence of TMSOTf gave the 18-α-glucuronide 9 a. The 18-β-glucuronide 15 b and the 20-β-glucuronide 16 b could be obtained by reaction of methyl 2,3,4-tri-O-isobutyryl-1α-glucuronate trichloroacetimidate 14 and aldosterone 21-acetate 8 in the presence of TMSOTf or BF ⋅OEt . Finally, reaction of aldosterone 21-acetate 8 and methyl 2,3,4-triacetyl-1α-glucuronate trichloroacetimidate 19 in the presence of TMSOTf gave the corresponding methyl 18-β-triacetylglucuronate 9 b, which was transformed into the desired aldosterone-18-β-glucuronide 3 by two enzyma- tic transformations.
醛固酮 1 是一种盐皮质激素，它对血压有很大的影响，其葡萄糖醛酸苷是检测几种疾病的重要标志物。在这里，我们描述了不同醛固酮-18-和 20-葡萄糖醛酸苷的化学合成。在 TMSOTf 的存在下，三甲基硅基 2,3,4-三乙酰基-1-β-葡萄糖醛酸甲酯 5b 和醛固酮二乙酸酯 11 的反应得到了 18-α-葡萄糖醛酸苷 9a。18-β-葡萄糖醛酸苷 15b 和 20-β-葡萄糖醛酸苷 16b 可以通过三氯乙酰亚胺酯 14 和 TMSOTf 或 BF ⋅OEt 存在下的醛固酮 21-乙酸酯 8 的反应得到。最后，在 TMSOTf 的存在下，醛固酮 21-乙酸酯 8 和三乙酰基-1α-葡萄糖醛酸甲酯三氯乙酰亚胺酯 19 的反应得到了相应的甲基 18-β-三乙酰基葡萄糖醛酸苷 9a，它通过两种酶促转化转化为所需的醛固酮-18-β-葡萄糖醛酸苷 3。
