SYNTHETIC AND PHYSICAL STUDIES OF ANTICANCER AGENTS

抗癌剂的合成和物理研究

• 批准号: 2178553
• 负责人: M ROBERT WILLCOTT
• 金额: $ 17.32万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-12-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2178553
• 关键词: X ray crystallography; antineoplastics; carbene; chemical cleavage; chemical hydration; chemical structure; drug design /synthesis /production; drug screening /evaluation; fluorine; image processing; ligands; radionuclides; radiotracer

The synthesis of novel hypervalent nonmetal species and studies of the chemical properties of these new types of organo-nonmetallic species is the primary goal of this research. Newly developed methods for the synthesis of ligands designed to strongly stabilize the bonding in these hypervalent species have been perfected. This males possible the formation of a wide variety of unprecedented types of compounds of main group elements on a large scale with rapid synthesis. These novel compounds have usually been requested for NCI anticancer drug screening, so the more rapid synthetic methodology will make more such species available in a much shorter time period than formation of our research products has required in previous years. The large scale synthetic methodology has made accessible a new compound which will be used to introduce 18F substituents into estrogens. This is expected to be later used in positron emission tomography for the imaging of human breast tumors. Methods recently developed for the synthesis of unique monodentate, bidentate, tridentate and tetradentate ligands for hypervalent nonmetal species will be used for the synthesis of a wide variety of main group element species. Many of these, which were already synthesized in our group, have important applications in synthetic organic chemistry (e.g., the commercially available Dess-Martin Periodinane and the Martin Sulfurane). An improved synthetic method for the Periodinane will be sought, since the starting material for orr current synthetic method has recently been found to be explosive under some conditions. The tetradentate ligand is a cis cyclobutanetetraol which makes square pyramidal four coordinate hypervalent species which are polymerizable, giving species to be studied in the solid state. Chiral hydride- substituted hypervalent species will be studied as possible reagents for the production of optically active reduced species by chirality transfer. A monodentate ligand to be studied is produced by attachment of a singlet electrophilic carbene to the nonmetal. It has been used to form the first chloronium ylide stable enough to provide an X-ray crystallographic structure.

新型超价非金属物种的合成及其结构研究 这些新型有机非金属化合物的化学性质 物种是本研究的首要目标。新开发的 设计用于强稳定的配体的合成方法 这些高价物种中的键已经完善。这 男性可能形成种类繁多的史无前例 大范围主族元素化合物的类型 快速合成。这些新化合物通常被要求 为了NCI抗癌药物的筛选，所以更快的合成 方法论将在更短的时间内提供更多这样的物种 比我们研究产品形成所需的时间更长 在前几年。大规模综合方法论已经取得了 可获得的新化合物将用于引入18F 将取代基转化为雌激素。预计这将在稍后用于 正电子发射断层成像技术在人体乳房成像中的应用 肿瘤。最近开发的合成独一无二的方法 单齿、双齿、三齿和四齿配体 超价非金属物种将用于合成一种 主族元素种类繁多。其中许多，它们 已经在我们组合成了，有重要的应用 在合成有机化学中(例如，商业上可获得的 Dess-Martin Perodinane和Martin Sulffane)。一种改进的 将寻求合成碘代烷的方法，因为 Orr当前合成方法的起始原料最近 在某些情况下被发现是爆炸性的。四齿类 配体是生成四方锥体的顺式环丁烷四醇 四个配位的高价物种是可聚合的，给出了 固体中待研究的物种。手性氢化物- 将尽可能研究被取代的高价物种 用于生产光学活性还原物种的试剂 手性转移。合成了待研究的单齿配体 通过将单重态亲电卡宾附着到非金属上。 它已经被用来形成第一个足够稳定的氯离子叶立德 以提供X射线晶体结构。