POLYVALENT IODINE AND DERIVED CHEMISTRY

多价碘及其衍生化学

• 批准号: 2468132
• 负责人: Peter J Stang
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2468132
• 关键词: alkynes; antineoplastics; chemical addition; chemical reaction; esters; phosphatase inhibitor; protease inhibitor

Acetylenes as well as Esters of all types (carboxylate, phosphate, sulfonate) are among the most ubiquitous, important and valuable functionalities and compounds in organic chemistry. Both play key roles in mechanistic, synthetic and bioorganic chemistry. Recently, we have discovered and prepared novel types of functionalized acetylenes, alkynyliodonium salts, as well as the hitherto unknown alkynyl esters. We shall capitalize and build upon this exciting development by elaborating the chemistry, as well as the medicinal and biochemistry of our new alkynyliodonium species and alkynyl esters. Specifically, we shall investigate: a) electrocyclic cycloadditions of both alkynyliodonium species and alkynyl esters; b) alkynylations and electrophilic acetylene chemistry, c) alkynyl amino acids via RC (triple bond) CIPhOTf; d) siloxyacetylene and ynolate chemistry; e) conjugated enyne formation via coupling of RC(triple bond)CIPhOTf; f) P-ylides; g) vinyliodonium species. We shall continue to examine the medicinal and biochemical,properties and significance of these compounds. Alkynyliodonium and phosphonium salts will be evaluated as potential new antitumor agents via "alkynylation" of biological nucleophiles. Data already in hand indicate that some members of this family are active against murine leukemia cells (L1210) and human-T-lymphoblast cells (Molt-4F) as well as the human-T-lymphocyte (MT-4) cells. Alkynyl carboxylates and phosphates will be examined as mechanism based protease and phosphatase inhibitors ("suicide substrates"). Preliminary results show that CH3C(triple bond)COC(O)Ar are potent inhibitors of serine based proteases. Similarly, n-BuC(triple bond)COP(O)(OEt)2 and related alkynyl phosphate esters are potent inhibitors of a bacterial triester phosphatase. This program of fundamental research on two relatively new types-and classes of compounds, namely alkynyliodonium salts and alkynyl esters, has major implications for synthetic, physical-organic, medicinal, as well as bioorganic chemistry.

乙炔以及所有类型的酯（羧酸酯，磷酸酯， 磺酸盐）是最普遍、最重要和最有价值的 有机化学中的官能团和化合物。 两者都扮演着关键角色 在机械、合成和生物有机化学中。 最近我们 发现并制备了新型官能化乙炔， 炔基碘鎓盐，以及迄今为止未知的炔基酯。 我们会把握这个令人振奋的发展， 阐述了化学，以及医学和生物化学， 我们的新炔基碘鎓物种和炔基酯。 我们特别 将调查：a）两个的电环加成 炔基碘鎓物质和炔基酯; B）炔基化和 c）通过RC的炔基氨基酸（三重 键）CIPhOTf; d）炔基乙炔和炔醇盐化学; e）共轭 通过RC（三键）CIPhOTf的偶联形成烯炔; f）P-叶立德; g） 乙烯基碘鎓类。 我们将继续研究其药用和生物化学特性， 这些化合物的重要性。 炔基碘鎓盐和鏻盐 将作为潜在的新的抗肿瘤剂通过“炔基化”的 生物亲核试剂 现有数据显示， 对鼠白血病细胞（L1210）有活性， 人T淋巴母细胞（Molt-4F）以及人T淋巴细胞 （MT-4）细胞。 炔基羧酸盐和磷酸盐将被检查为 基于蛋白酶和磷酸酶抑制剂（“自杀 基质”）。 初步结果表明，CH 3C（三键）COC（O）Ar 是丝氨酸基蛋白酶的有效抑制剂。 类似地，n-BuC（三重 键）COP（O）（OEt）2和相关的炔基磷酸酯是有效的 细菌三酯磷酸酶的抑制剂。 这两个相对较新的类型的基础研究计划-和 化合物的种类，即炔基碘鎓盐和炔基酯， 对合成的、物理有机的、药用的， 以及生物有机化学。