Belostotskii Anatoly M, Goren Zafrir, Gottlieb Hugo E
Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel.
J Nat Prod. 2004 Nov;67(11):1842-9. doi: 10.1021/np049895+.
(13)C DNMR studies of codeine and sinomenine (derivatives of N-Me morphinan) indicated that N-inversion-C-N rotation (NIR) is unusually fast for these substituted piperidines when compared with other N-Me piperidines. Since only broadening, but no signal splitting, was reached at low temperatures and the difference of chemical shifts (Delta delta) for individual conformers with the equatorially and axially oriented N-Me substituent was unavailable, the limits of the NIR barrier for these amines were determined by line shape analysis using Delta delta values provided by ab initio calculations. On the basis of the comparison of experimentally determined (13)C NMR chemical shifts for tropane conformers with the ones calculated at different theory levels for this N-Me piperidine, the B3LYP/6-31G(p)/GIAO level was chosen as a sufficiently accurate method for calculations of Delta delta. By this new "semiempirical" procedure of line shape analysis the NIR barrier for the studied morphinans lies within a 25-27 kJ mol(-1) (6.0-6.5 kcal mol(-1)) range. A low NIR barrier for morphine alkaloids is supposed to be an important factor in the activation of morphine receptor.
对可待因和青藤碱（N-甲基吗啡喃衍生物）的(13)C核磁共振研究表明，与其他N-甲基哌啶相比，这些取代哌啶的N-反转-C-N旋转（NIR）异常迅速。由于在低温下仅出现谱线变宽，未出现信号分裂，且无法获得具有赤道和轴向取向N-甲基取代基的各个构象异构体的化学位移差值（Δδ），因此通过使用从头算计算提供的Δδ值进行线形分析，确定了这些胺类的NIR势垒极限。基于对托烷构象异构体的实验测定(13)C核磁共振化学位移与针对该N-甲基哌啶在不同理论水平计算得到的化学位移进行比较，选择B3LYP/6-31G(p)/GIAO水平作为计算Δδ的足够精确的方法。通过这种新的线形分析“半经验”程序，所研究吗啡喃的NIR势垒在25 - 27 kJ mol(-1)（6.0 - 6.5 kcal mol(-1)）范围内。吗啡生物碱的低NIR势垒被认为是激活吗啡受体的一个重要因素。
