SYNTHESIS, ACTIVITY, AND REACTIVITY OF 9-BORASTEROIDS

9-硼甾醇的合成、活性和反应性

• 批准号: 3151162
• 负责人: THOMAS ALLAN BRYSON
• 金额: $ 7.01万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-05-01 至 1986-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3151162
• 关键词: androstenedione; boranes; boron; cortisone; cycloalkene; drug design /synthesis /production; drug metabolism; drug screening /evaluation; stereochemistry; steroid biosynthesis; unsaturated fatty acids

It is proposed to prepare racemic cortisone by two very different routes and optically active cortisone using a resolved starting material for one of these routes the overall approach to the corticoid steroids is a test of boron annelation (hydroboration and carbonylation or equivalent reaction) as a synthetic tool. In addition the synthesis of androstandione, fichtelite, hibanone, kaurene and the basic skeletal system of aphidicolin (and similar compounds) are proposed employing newly developed variations on boron annelation. These propositions are designed (a) to carefully evaluate a new approach to steroid (and natural product) synthesis, (b) to provide medicinally important drugs (cortisone, etc.), as well as allow for evaluation (testing) of a new class of "hetero"-steroids (borasteroids) and (c) to answer certain important chemical questions concerning the usage of carboranes in complex natural product synthesis. It is of chemical significance that a triene will be converted to cortisone and optically active cortisone. Various dienes have been designed to evaluate the effect of "remote" Lewis base and other influences on hydroboration/carbonylation in forming the other natural product target systems. All compounds prepared will be evaluated for actvity with general screening being done at Lederle' Drug Co., Shell Oil and with certain specific types of activity (anticancer, antileukemic) being done at U.S.C.

提出了通过两种非常不同的路线制备外消旋可的松 和光学活性可的松，其中一种使用拆分的起始材料， 在这些途径中，皮质类固醇的总体方法是测试 硼氢化（硼氢化和羰基化或等效反应） 作为一种合成工具 除了雄甾烷二酮的合成外， 菲希特石、希巴酮、贝壳杉烯和蚜虫菌素的基本骨骼系统 (and类似的化合物）提出采用新开发的变体 关于硼铵。 这些建议的目的是（a）仔细 评价类固醇（和天然产物）合成的新方法，（B） 提供医学上重要的药物（可的松等），以及允许 评估（测试）一类新的“杂”类固醇（borasteroids）， (c)来回答一些重要的化学问题， 碳硼烷在复杂天然产物合成中的应用。 它是化学的 重要的是，三烯将被转化为可的松， 活性可的松 设计了不同的二烯来评价其效果 “远程”刘易斯碱和其他对硼氢化/羰基化的影响 形成其他天然产物靶系统。 所有化合物 将在以下条件下进行一般筛选，评价制备的活性： 深圳市华诚医药有限公司壳牌石油和某些特定类型的活动 （抗癌，抗白血病）在南加州进行。