SYNTHESIS OF OPTICALLY PURE INHALATION ANESTHETICS

常用的吸入麻醉药氟烷、恩氟烷和异氟烷 各自含有单个手性碳原子，因此各自以50/50的比例存在， 对映异构体的（外消旋）混合物;所有药物均在临床上以 外消旋形式。 事实上，我们对麻醉剂和 活性或这些试剂的纯对映体的毒性。 最近 麻醉研究的进展表明，特定的活性部位 麻醉剂与膜结合蛋白的结合可能起作用 在麻醉作用的机制中。 与酶的直接相互作用 结合位点通常对底物立体结构高度敏感。 因此，评价对映体的相对活性和毒性 临床上常用的吸入麻醉药， 理论，重要性。 我们建议开发合成方法，以提供每种 光学纯形式的氟烷、恩氟烷和异氟烷的对映体， 并以足够的量用于体外评价。 最近描述的 在我们的初步研究中将使用萤火虫荧光素酶测定。 我们的合成 氟烷、恩氟烷和异氟烷的方法将利用 拆分技术，或进行光学合成反应， 诱导

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.