POLYVALENT IODINE AND DERIVED CHEMISTRY

多价碘及其衍生化学

• 批准号: 6339636
• 负责人: Peter J Stang
• 金额: $ 1.9万
• 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/6339636
• 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(羧酸盐、磷酸盐、 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方面。最近，我们有 发现并制备了新型官能化乙炔， 烷基碘盐，以及迄今未知的炔基酯。 我们将利用这一令人振奋的发展并通过 阐述了其化学以及药物和生物化学。 我们的新的炔基碘物种和炔基酯。具体来说，我们 应调查：a)两者的电环加成反应 乙炔基碘物种和乙炔基酯；b)乙炔基化和 亲电乙炔化学，c)通过RC(三重)的炔基氨基酸 键)CphOTf；d)硅氧乙炔和苯乙酸酯化学；e)共轭 通过RC(三键)CIPhOTf；f)P-叶立德偶联生成烯炔；g) 偏碘齿菌属物种。 我们将继续检查药用和生化，性质和 这些化合物的意义。烷基碘和膦盐 将被评价为潜在的新的抗肿瘤药物，通过 生物亲核者。手头已有的数据表明，一些成员 对小鼠白血病细胞(L1210)和 人T淋巴母细胞(Molt-4F)和人T淋巴细胞 (MT-4)细胞。炔基羧酸盐和磷酸盐将被检测为 基于机制的蛋白水解酶和磷酸酶抑制剂(“自杀 初步结果表明，CH3C(三键)COC(O)是 是丝氨酸蛋白酶的有效抑制剂。同样，n-Buc(三元组 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。 这个项目是关于两个相对较新的类型的基础研究-和 一类化合物，即烷基碘盐和炔基酯， 对合成的、物理的有机的、医药的、如 以及生物有机化学。