A novel mercapto-bisphosphonate as an efficient anticalcification agent for bioprosthetic tissues
A novel mercapto-bisphosphonate as an efficient anticalcification agent for bioprosthetic tissues
复制标题
DOI：
10.1016/j.jorganchem.2004.10.011
复制
发表时间：
2005-05-16
影响因子：
2.3
通讯作者：
Levy, RJ
中科院分区：
文献类型：
--
作者：
Alferiev, IS;Connolly, JM;Levy, RJ
据报道，通过将胱胺亲核加成至亚乙烯基二膦酸 (1)，然后用 Me3P 还原二硫键，合成了 2-(2-巯基乙基氨基)亚乙基-1,1-二膦酸 (2)（总产率 > 90%）。 1 与半胱胺反应形成异构体 2-(2-氨基乙硫基)亚乙基-1,1-二膦酸酯 (3)，收率几乎定量。与已知的2-缩亚乙基-1,1-二膦酸酯相比，2的硫醇基团在pH 7的水中与环氧环的反应速度快30倍以上。硫醇基团的消除被观察为用膦还原二硫化物时的副反应。在 2 存在的情况下，用三缩水甘油胺稳定生物假体组织，导致 2 通过环氧-SH 反应共价固定；这可以将生物人工心脏瓣膜组织的长期钙化抑制到几乎无法检测到的水平。 (c) 2004 Elsevier B.V. 保留所有权利。
The synthesis of 2-(2-mercaptoethylamino)ethylidene-1,1-bisphosphonic acid (2) is reported (overall yield > 90%), via nucleophilic addition of cystamine to vinylidene-bisphosphonic acid (1) followed by reduction of disulfide bonds with Me3P. Reaction of 1 with cysteamine forms the isomeric 2-(2-aminoethylthio)ethylidene-1,1-bisphosphonate (3) in an almost quantitative yield. Thiol groups of 2 in water at pH 7 react with epoxy rings more than 30 times faster compared to the known 2-mereaptoethylidene-1,1-bisphosphonate. Elimination of the thiol group is observed as a side-reaction in the reduction of disulfides with phosphines. Stabilization of bioprosthetic tissues with triglycidylamine in the presence of 2 results in covalent immobilization of 2 via an epoxy-SH reaction; this inhibits the long-term calcification of bioprosthetic heart valve tissues to almost undetectable levels. (c) 2004 Elsevier B.V. All rights reserved.