Zheng X, Day C, Gollamudi R
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis 38163, USA.
Chirality. 1995;7(2):90-5. doi: 10.1002/chir.530070207.
The stereoisomers of alpha,alpha'-bis[3-(N,N-diethylcarbamoyl)-piperidino]-p-xylene (1) were synthesized. Rac ethyl nipecotate was resolved by diastereomeric (-)-D- and (+)-L-tartrate salt formation. The enantiomeric esters were hydrolyzed to the corresponding nipecotic acids, which were then converted into t-BOC derivatives. Treatment of the latter with diethylamine/isobutyl chloroformate and removal of the t-BOC protecting group afforded (R)- and (S)-N,N-diethylnipecotamides. Condensation of the latter with alpha,alpha'-dibromo-p-xylene gave (R,R)- and (S,S)-1. The meso-diastereomer was obtained by stereospecific synthesis in addition to our earlier procedure involving fractional crystallization of the diastereomeric mixture obtained by synthesis. The latter was resolved earlier into 1A, 1B, and 1C using chiral high-performance liquid chromatography (HPLC). Based on the stereospecific synthesis now achieved, 1A and 1B are assigned the configurations, (R,R) and (S,S) respectively, and 1C is assigned the meso configuration. The (R,S) structure of the latter is also confirmed by X-ray crystallography.
合成了α,α'-双[3-(N,N-二乙基氨基甲酰基)-哌啶基]-对二甲苯(1)的立体异构体。通过形成非对映体(-)-D-和(+)-L-酒石酸盐拆分外消旋的乙基哌啶酸。将对映体酯水解为相应的哌啶酸，然后将其转化为叔丁氧羰基衍生物。用二乙胺/氯甲酸异丁酯处理后者并除去叔丁氧羰基保护基，得到(R)-和(S)-N,N-二乙基哌啶酰胺。将后者与α,α'-二溴对二甲苯缩合得到(R,R)-和(S,S)-1。除了我们早期通过合成得到的非对映体混合物分步结晶的方法外，还通过立体专一性合成得到了内消旋非对映体。后者早些时候使用手性高效液相色谱(HPLC)拆分为1A、1B和1C。基于现在实现的立体专一性合成，1A和1B分别被指定为(R,R)和(S,S)构型，1C被指定为内消旋构型。后者的(R,S)结构也通过X射线晶体学得到证实。
