Ceska Slov Farm. 2021 Spring;70(1):7-17.
Since the advent of nitric oxide, diethyl ether, chloroform and cyclopropane, the greatest advancement in the area of general inhalational anesthetics has been achieved by the introduction of fluorinated anesthetics and the relevant chiral techniques. This progress led to marked decrease in mortality rates in anesthesia. In the group of chiral fluorinated compounds, halothane (Fluotan®), isoflurane (Foran®), desflurane (Supran®) and enflurane (Ehran®) are deployed as volatile anesthetics. Chiral anesthetics possess a stereogenic center in their molecules and thus exist as two enantiomers (S)-(+) and (R)-(-). Although these chiral anesthetics are used as racemates, it is crucial to study besides the bioactivities of the racemic compounds also the biological activity and other properties of the particular enantiomers. The present survey discusses the drug category known as inhalational anesthetics in regard to their chiral aspects. These compounds exhibit marked differences between the (R) and (S)-enantiomers in their pharmacodynamics, pharmacokinetics and toxicity. The main analytical technique employed in the enantioseparation of these compounds is gas chromatography (GC). This review lists the individual chiral phases (chiral selectors) used in the enantioseparation as well as in pharmacokinetic studies. The possibilities of preparation of these compounds in their enantiomerically pure form by means of stereoselective synthesis are also mentioned.
自一氧化二氮、乙醚、氯仿和环丙烷问世以来,氟麻醉剂和相关的手性技术的引入在全身吸入麻醉领域取得了最大的进展。这一进展显著降低了麻醉死亡率。在手性氟代化合物组中,氟烷(Fluotan®)、异氟烷(Foran®)、地氟烷(Supran®)和恩氟烷(Ehran®)被用作挥发性麻醉剂。手性麻醉剂在其分子中具有一个手性中心,因此存在两种对映异构体(S)-(+)和(R)-(-)。尽管这些手性麻醉剂作为外消旋体使用,但除了研究外消旋化合物的生物活性外,研究特定对映异构体的生物活性和其他性质也至关重要。本综述讨论了作为吸入麻醉剂的药物类别,涉及它们的手性方面。这些化合物在药效学、药代动力学和毒性方面,(R)和(S)对映体之间存在显著差异。在手性分离这些化合物中使用的主要分析技术是气相色谱(GC)。本综述列出了用于对映体分离以及药代动力学研究的各个手性相(手性选择器)。还提到了通过立体选择性合成制备这些化合物对映体纯形式的可能性。