Synthesis and Applications of Alpha-Aminophosphonothioic Acids

在有机合成计划的支持下，蒙大拿大学化学系的Charles M. Thompson教授研究了α -氨基膦硫酸（APTA）的合成和应用。APTA是一类新的分子，其中α -氨基酸的羧酸基团被磷硫酸部分所取代。APTA对磷具有手性，另外还可以在P(O)SH和P(S)OH形式之间表现出互变异构。汤普森教授正在开发新的合成路线，以制备外消旋和非外消旋形式的APTA，依靠在亚胺中添加硫代磷酸盐、aza-Claisen重排和从磷酸盐中衍生的1,3- n， c -离子的烷基化。此外，他利用互变异构平衡生成二硫键形成位点，提供了肽链内和链间连接的可能性，并在含有APTA的合成肽中生成了新的β -片结构。APTA作为不对称过渡态类似抑制剂的能力，以及作为分子系统的中心元素，在金属离子络合时显示显着的构象变化的能力也在探索中。用“非天然”氨基酸或功能相关衍生物替代生物蛋白质中的氨基酸，为修饰和控制蛋白质的结构和反应性提供了可能。在有机合成计划的支持下，蒙大拿大学化学系的Charles M. Thompson教授进行了不寻常的氨基酸类似物的合成和研究，称为α -氨基膦酸（APTA），其中P(O)SH基团取代了氨基酸中的C(O)OH基团。APTA在模型蛋白质结构中的结合允许使用垂坠的硫原子来影响蛋白质链的连接，从而提供新的蛋白质结构。汤普森教授还探索了含有APTA的蛋白质可能作为各种酶抑制剂的可能性，并将APTA作为设计分子的中心元素，设计分子形式在与金属离子相互作用时发生极端变化。

With the support of the Organic Synthesis Program, Professor Charles M. Thompson, of the Department of Chemistry at the University of Montana, studies the synthesis and applications of alpha-aminophosphonothioic acids (APTA's). APTA's are a new class of molecules in which the carboxylic acid group of an alpha-amino acid has been replaced by a phosphonothioic acid moiety. The APTA's are chiral at phosphorus and additionally can display tautomerization between the P(O)SH and P(S)OH forms. Professor Thompson is developing new synthetic routes for the preparation of APTA's in both racemic and nonracemic form, relying on the addition of thiophosphites to imines, aza-Claisen rearrangement, and alkylation of 1,3-N,C-dianions derived from phosphonates. In addition, he exploits the tautomeric equilibrium to generate a site for disulfide bond formation, offering the possibility of peptide intra-strand and inter-chain linkage and the generation of novel beta-sheet structures in synthetic peptides incorporating APTA's. The ability of APTA's to serve as asymmetric transition state analog inhibitors and to serve as central elements in molecular systems designed to display marked conformational changes upon metal ion complexation are also under exploration. Replacement of the amino acids in biological proteins with `unnatural` amino acids or functionally related derivatives offers the possibility of modifying and controlling the structure and reactivity of proteins. With the support of the Organic Synthesis Program, Professor Charles M. Thompson, of the Department of Chemistry at the University of Montana, carries out the synthesis and study of unusual amino acid analogs known as alpha-aminophosphonothioic acids (APTA's), in which a P(O)SH group replaces the C(O)OH group found in amino acids. The incorporation of APTA's in model protein structures allows the use of the pendant sulfur atoms to effect the linking of protein chains, affording access to novel protein architectures. Professor Thompson also explores the possibility that APTA-containing proteins may function as inhibitors for various enzymes, and additionally uses APTA's as central elements in the design of molecules designed to undergo extreme changes in molecular form upon interaction with metal ions.