SYNTHESIS OF OPTICALLY PURE INHALATION ANESTHETICS

常用的吸入麻醉剂氟烷、安氟醚和异氟烷 每一个都含有一个手性碳原子，因此每个都以50/50的比例存在 (外消旋)对映体的混合物；所有的都在临床上给药 外消旋形式。事实上，对麻醉剂和麻醉剂都一无所知 这些试剂的纯对映体的活性或毒性。近期 麻醉研究的进展表明，特定的、活跃的部位 麻醉剂与膜结合蛋白的结合可能起到一定作用 在麻醉作用的机制中。与酶的直接相互作用 结合部位通常对底物立体结构高度敏感。 因此，对映体的相对活性和毒性的评价 常用吸入性麻醉药的临床应用 理论上的，重要的。 我们建议开发综合方法学，以提供每一个 光学纯的氟烷、安氟醚和异氟烷的对映体， 并有足够的数量进行体外评估。最近描述的一种 萤火虫荧光素酶测定将在我们的初步研究中使用。我们的合成材料 氟烷、安氟醚和异氟烷的使用方法 拆分技术，或用光学方法进行的合成反应 归纳法。

The commonly used inhalant anesthetics halothane, enflurane, and isoflurane each contain a single chiral carbon atom and hence each exists as a 50/50 (racemic) mixture of enantiomers; all are administered clinically in racemic form. In fact, nothing is known about either the anesthetic activity or the toxicity of the pure enantiomers of these agents. Recent developments in anesthesia research suggest that specific, active site binding of anesthetic agents with membrane-bound proteins may play a role in the mechanism of anesthetic action. Direct interaction with enzyme binding sites is usually highly sensitive to substrate stereostructure. Thus, evaluation of the relative activity and toxicity of the enantiomers of commonly used inhalant anesthetics is of clinical, as well as theoretical, importance. We propose to develop synthetic methodology to provide each of the enantiomers of halothane, enflurane, and isoflurane in optically pure form, and in sufficient quantities for in vitro evaluation. A recently described firefly luciferase assay will be used in our initial study. Our synthetic approaches to halothane, enflurane, and isoflurane will utilize either resolution techniques, or synthetic reactions which proceed with optical induction.