Khalil M A, Lay J C, Lee H J
J Pharm Sci. 1985 Feb;74(2):180-3. doi: 10.1002/jps.2600740215.
The synthesis and anti-inflammatory activity of a new steroidal acid ester, methyl 11 beta-hydroxy-3,20-1,4-pregnadien-21-oate (5), are described. This compound has been prepared via three different synthetic routes. The first involves oxidation of the benzoate 3 to the aldehyde 4 followed by a Mattox-type rearrangement of the side chain in conjunction with elimination of the benzoyloxy group. The second method, prolonged reaction of 1-dehydrocorticosterone (8) with methanolic cupric acetate, affords methyl ester 5 in low yield. The third approach consists of selective oxidation at C-20 of the methyl 11 beta, 20 alpha and 20 beta-dihydroxy-3-oxo-1,4-pregnadien-21-oates (7a and 7b) with sulfur trioxide-pyridine complex. The local anti-inflammatory activities of the new ester 5 and intermediates 3, 4, 7a and 7b were determined by the cotton-pellet granuloma assay in rats. The anti-inflammatory activity of the title compound is equal to that of the parent steroid, prednisolone. However, unlike the latter compound, the ester does not cause reduction of adrenal and thymus weights or a lowering of plasma corticosterone levels.
描述了一种新的甾体酸酯11β-羟基-3,20-孕甾二烯-21-酸甲酯（5）的合成及其抗炎活性。该化合物通过三种不同的合成路线制备。第一种方法是将苯甲酸酯3氧化为醛4，然后进行侧链的马托克斯型重排并消除苯甲酰氧基。第二种方法是使1-脱氢皮质酮（8）与醋酸铜甲醇溶液长时间反应，以低产率得到甲酯5。第三种方法是用三氧化硫-吡啶络合物对11β,20α-二羟基-3-氧代-1,4-孕甾二烯-21-酸甲酯（7a）和11β,20β-二羟基-3-氧代-1,4-孕甾二烯-21-酸甲酯（7b）在C-20位进行选择性氧化。通过大鼠棉球肉芽肿试验测定了新酯5及中间体3、4、7a和7b的局部抗炎活性。标题化合物的抗炎活性与母体甾体泼尼松龙相当。然而，与后一种化合物不同的是，该酯不会导致肾上腺和胸腺重量减轻或血浆皮质酮水平降低。
