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.

乙酰基烯和各种类型的酯（羧酸盐，磷酸盐， 磺酸盐）是最普遍，最重要，有价值的 有机化学中的功能和化合物。 两者都扮演关键角色 在机械，合成和生物有机化学中。 最近，我们有 发现并制备了新型的功能化乙炔， Alkynyliodonium盐，以及迄今未知的Alkynyl酯。 我们将通过 详细说明化学以及药物和生物化学 我们的新酸性二氧化碳和藻类酯。 具体来说，我们 应调查：a）两者的电循环环加成 Alkynyliodonium物种和Alkynyl酯； b）Alkynylations和 亲电乙炔化学，c）通过RC（三重）烷基氨基酸（三重 键）ciphotf; D）硅氧基乙烯和Ynaly化学； e）共轭 通过RC（三键）CIPHOTF耦合Enyne形成； f）p甲基; g） 乙烯基二元物种。 我们将继续检查药用和生化，特性和 这些化合物的意义。 炔烃和磷盐 将通过“藻类”的“藻类”评估为潜在的新抗肿瘤剂 生物亲核试剂。 数据中的数据表明一些成员 这个家族对鼠白血病细胞（L1210）和 人-T浓细胞细胞（MOLT-4F）以及人类-T淋巴细胞 （MT-4）细胞。 Alkynyl羧酸盐和磷酸盐将被检查为 基于机理的蛋白酶和磷酸酶抑制剂（自杀 底物”）。初步结果表明CH3C（三键）COC（O）AR 是丝氨酸蛋白酶的有效抑制剂。 同样，n-buc（三重 债券）COP（O）2和相关的Alkynyl磷酸酯是有效的 细菌三酯磷酸酶的抑制剂。 这项针对两种相对较新类型的基础研究和 化合物类别，即炔烃盐和藻类酯， 对合成，物理有机，药用具有重大影响 以及生物有机化学。