POLYVALENT IODINE AND DERIVED CHEMISTRY

多价碘及其衍生化学

• 批准号: 6343004
• 负责人: Peter J Stang
• 金额: $ 30.32万
• 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 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6343004
• 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.

乙炔以及各种类型的酯类(羧酸酯、磷酸酯、