Jaen J C, Caprathe B W, Priebe S, Wise L D
Department of Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Pharm Res. 1991 Aug;8(8):1002-5. doi: 10.1023/a:1015800923078.
Reduced haloperidol (RHAL) is the best known metabolite of haloperidol (HAL), having been identified in humans, rats, and guinea pigs. Since RHAL contains an asymmetric center, it can exist in two possible enantiomeric forms. However, the enantiomeric composition of the RHAL formed from HAL in vivo has never been reported. As a first step toward the enantiomeric analysis of biological samples, we have developed an efficient and stereospecific synthesis of (+)- and (-)-RHAL from readily available commercial materials. We have also identified an enantioselective chromatographic method using a chiral HPLC stationary phase which can detect as little as 1% of either enantiomer in synthetic samples of RHAL enantiomers.
还原氟哌啶醇（RHAL）是氟哌啶醇（HAL）最知名的代谢产物，已在人类、大鼠和豚鼠体内被鉴定出来。由于RHAL含有一个不对称中心，它可以以两种可能的对映体形式存在。然而，HAL在体内形成的RHAL的对映体组成从未被报道过。作为生物样品对映体分析的第一步，我们已经从容易获得的商业原料开发出了一种高效且立体专一的（+）-和（-）-RHAL的合成方法。我们还确定了一种使用手性高效液相色谱固定相的对映体选择性色谱方法，该方法在RHAL对映体的合成样品中可以检测到低至1%的任何一种对映体。
