HALOGENATED BIOGENIC AMINES IN BIOCHEMISTRY AND PHARMACOLOGY

生物胺在神经传递、新陈代谢和 对各种生理过程的控制。使用各种合成材料 方法，包括我们开发的新程序，我们有 合成了一系列不同含氟量取代的生物胺 吊环位置。由于它的体积很小，高度很高 电负性，氟是氢的一种非常有利的替代品 在这些类似物中。它们的生物学特性和用途 环氟化生物胺已被证明是非常有益的。 并继续在众多研究中找到应用，包括 运输、储存、释放、代谢等机制的研究 以及这些胺的作用方式。特别重要的是 发现6-氟肾上腺素是一种选择性的α-肾上腺素能 激动剂和2-氟肾上腺素是一种选择性β-肾上腺素能 激动剂。解释这些结果的机制包括：1) C-F键对激动剂-受体相互作用的直接影响 C-F键对分子构象的间接影响 乙醇胺侧链。新类似物的测试结果 合成来探索这些机制还没有明确的区分 在这两种基本机制之间。含氟类似物与 克隆了野生型和突变型肾上腺素能受体 试图确定受体蛋白上的特定位置 负责氟诱导的肾上腺素能选择性。我们有 苏氨酸和6-苏氨酸的立体选择性合成研究进展 氟二羟基苯丝氨酸(F-DOPS)。一种新的合成方法 氟化和多氟藜芦醛，基于直接 亲电氟化，已经实现，我们已经准备好了所有 藜芦醛的一氟和二氟类似物以及 三氟杂多醛。这些都被用来准备 相应的生物胺及其氨基酸前体。 单、二、三氟类似物相互作用的研究 多巴胺与D-1、D-2和D-3受体的结合 出去。氨基环丙烷羧酸(ACCA)已经被其他人证明 以提供保护，免受中枢神经元中风的损害。

Biogenic amines play key roles in neurotransmission, metabolism, and in control of various physiological processes. Using a variety of synthetic methodologies, including novel procedures developed by us, we have prepared a series of biogenic amines with flourine substituted at various ring-positions. By virtue of its very small size and high electronegativity, flourine is a very favorable replacement for hydrogen in these analogues. The biological properties and usefulness of these ring-fluorinated biogenic amines have proved to be extremely rewarding and continue to find applications in a multitude of studies, including research on the mechanisms of transport, storage, release, metabolism, and modes of action of these amines. Of particular significance was the discovery that 6-flouronorepinephrine is a selective alpha-adrenergic agonist and 2-fluoronorepinephrine is a selective beta-adrenergic agonist. Mechanisms considered to explain these results include; 1) a direct effect of the C-F bond on agonist-receptor interaction or 2) an indirect effect of the C-F bond on the conformation of the ethanolamine side-chain. The results of testing of new analogues synthesized to probe these mechanisms have not clearly differentiated between these two basic mechanisms. Binding of fluorinated analogues to cloned wild-type and mutant adrenergic receptors has been carried out in an attempt to identify specific sites on the receptor protein responsible for fluorine-induced adrenergic selectivities. We have developed stereoselective syntheses of threo-2-and 6- fluorodihydroxyphenylserine (fluoro-DOPS). A new synthesis of fluorinated and polyfluorinated veratraldehydes, based on direct electrophilic fluorination, has been realized, and we have prepared all mono- and difluorinated analogues of veratraldehyde as well as trifluorovertraldehyde. These are being used to prepare the corresponding biogenic amines and their amino acid precursors. Examination of the interactions of the mono-, di-, and trifluoroanalogues of dopamine with D-1, D-2, and D-3 dopamine receptors has been carried out. Aminocyclopropane carboxylic acid (ACCA) has been shown by others to provide protection from damage due to stroke of central neurons.