Design and synthesis of an aminobenzo-15-crown-5-labeled estradiol tethered with disulfide linkage
Design and synthesis of an aminobenzo-15-crown-5-labeled estradiol tethered with disulfide linkage
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DOI：
10.1016/j.tet.2004.09.109
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发表时间：
2004-12-13
期刊：
影响因子：
2.1
通讯作者：
Kurihara, T
中科院分区：
文献类型：
--
作者：
Harusawa, S;Yoshida, K;Kurihara, T
基于E-2和标记的E-2与固定化抗体之间的竞争，提出了一种测量尿液或血液中17β-雌二醇(E1)的新方法(电免疫测定法)。为了评估原理，3-{4-[17β-羟基-1,3,5(10)-雌三烯-3-基氧基]丁基二硫基}-N-(6,7,9,10,12,13,15,16-八氢-5,8,11,14,17-五氧杂苯并环十五烯-2-基) 琥珀酸(1)被设计和合成为一种新型的含有二硫键的氨基苯并-15-冠-5的E-2。分别由巯基琥珀酸7和4,4-二硫代二丁酸12有效合成了两种硫醇中间体5b和19c。研究了由反应性较低的硫醇形成二硫键，并且可以使用4-苯基-1,2,4-三唑啉-3,5-二酮(PTAD)从5b和19c形成不对称二硫键20c。然后，在20℃下除去TMS-和烯丙基-保护基团，成功得到含冠醚的E-2 1。(C) 2004 Elsevier Ltd.保留所有权利。
A novel measuring method (electroimmunoassay) of 17beta-estradiol (E,) in urine or blood was proposed on the basis of a competition between E-2 and a labeled E-2 against an immobilizing antibody. To evaluate the principle, 3-{4-[17beta-hydroxy-1,3,5(10)-estratrien-3-yloxy]butyldisulfanyl}-N-(6,7,9,10,12,13,15,16-octahydro-5,8,11,14,17-pentaoxabenzocyclopentadecen-2-yl) succinamic acid (1) was designed and synthesized as a novel aminobenzo-15-crown-5-containing E-2 tethered with disultide linkage. Two thiol-intermediates 5b and 19c were efficiently synthesized from mercaptosuccinic acid 7 and 4,4-dithiodibutyric acid 12, respectively. Formations of disulfide linkages from less reactive thiols were examined and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) could be employed for the formation of an unsymmetrical disulfide 20c from 5b and 19c. Then, removal of TMS- and allyl-protecting groups in 20c successfully afforded the crown ether-containing E-2 1. (C) 2004 Elsevier Ltd. All rights reserved.