Synthesis and Applications of Alpha-Aminophosphonothioic Acids

α-氨基硫代膦酸的合成及应用

• 批准号: 9807469
• 负责人: Charles Thompson
• 金额: $ 23.8万
• 依托单位: University of Montana
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9807469&HistoricalAwards=false
• 关键词: Synthesis; Applications; Alpha; Aminophosphonothioic; Acids

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 APTA's are a new class of molecules in which the carboxylic acid group of an alpha-amino acid has been replaced by a phosphonothioic acid moiety.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.

在有机合成计划的支持下，查尔斯M。 蒙大拿大学化学系的汤普森说， 研究了α-氨基硫代膦酸的合成及应用 酸（APTA）。 APTA是一类新分子，其中 α-氨基酸的羧酸基团已被取代， 硫代膦酸部分。 APTA在磷上是手性的， 还可显示P（O）SH和P（S）OH之间的互变异构， forms. 汤普森教授正在开发新的合成路线， 外消旋和非外消旋形式的APTA的制备，依赖于 硫代亚磷酸酯与亚胺的加成，氮杂-克莱森重排， 衍生自膦酸酯的1，3-N，C-二价阴离子的烷基化。 此外，本发明还提供了一种方法， 他利用互变异构平衡来产生二硫键 键形成，提供了肽链内的可能性， 链间连接和产生新的β-折叠结构， 掺入APTA的合成肽。 APTA的服务能力 作为不对称过渡态类似物抑制剂， 分子系统中的元件，设计用于显示标记的构象 对金属离子络合的变化也在探索中。 生物蛋白质中的氨基酸被“非天然”氨基酸取代 氨基酸或功能相关的衍生物提供了 修饰和控制蛋白质的结构和反应性。 与 有机合成计划的支持，教授查尔斯M。 蒙大拿大学化学系的汤普森说， 进行合成和研究不寻常的氨基酸类似物已知 作为α-氨基硫代膦酸（APTA），其中P（O）SH基团 取代氨基酸中的C（O）OH基团。 掺入 APTA在模型蛋白质结构中允许使用侧硫 原子来影响蛋白质链的连接，从而获得新的 蛋白质结构 汤普森教授还探讨了 含有APTA的蛋白质可以作为各种 酶，并且另外使用APTA作为设计中的中心元素， 分子的设计经历极端变化的分子形式， 与金属离子的相互作用。