SYNTHETIC AND PHYSICAL STUDIES OF ANTICANCER AGENTS

抗癌剂的合成和物理研究

• 批准号: 3291390
• 负责人: JAMES C MARTIN
• 金额: $ 14.83万
• 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 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3291390
• 关键词: X ray crystallography; antineoplastics; carbene; chemical cleavage; chemical hydration; chemical structure; drug design /synthesis /production; drug screening /evaluation; image processing; ligands; 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.

新型高价非金属配合物的合成及其催化性能研究 这些新型有机非金属化合物的化学性质 物种是这项研究的主要目标。 新开发 设计用于强稳定的配体的合成方法 这些超价物质的键合已经完善 这 男性可能形成各种各样的前所未有的 主族元素的化合物类型， 快速合成 这些新化合物通常被要求 用于NCI抗癌药物筛选，使合成更快速 这种方法将在更短的时间内提供更多的此类物种。 比我们的研究产品的形成所需的时间 前几年 大规模合成方法学使 一种新的化合物将被用来引入18F 取代基转化为雌激素。 预计这将在以后用于 正电子发射体层摄影术用于人体乳房成像 肿瘤的 最近开发的用于合成独特的 单齿、二齿、三齿和四齿配体， 高价非金属物质将用于合成 主族元素种类繁多。 其中许多， 已经在我们的团队中合成了， 在合成有机化学中（例如，市售 戴斯-马丁高碘烷和马丁硫烷）。 一种改进 将寻求高碘烷的合成方法，因为 用于Orr当前合成方法的起始材料最近 在某些条件下具有爆炸性。 的四配 配体是一个顺式环丁烷四醇， 四个配位的超价物质，它们是可聚合的， 在固体状态下研究的物种。 手性氢化物- 将尽可能研究取代的高价物质 用于制备旋光还原物质的试剂， 手性转移 制备了一种待研究的单齿配体 通过将单线态亲电卡宾连接到非金属上。 它已被用来形成第一个足够稳定的氯叶立德 以提供X射线晶体结构。