环状核苷磷酸酯前药的结构：探讨。
Structure of cyclic nucleoside phosphonate ester prodrugs: an inquiry.
机构信息
Department of Chemistry, University of Southern California, Los Angeles, California 90089-0744, United States.
出版信息
J Org Chem. 2012 Jan 6;77(1):684-9. doi: 10.1021/jo201735f. Epub 2011 Nov 30.
Abstract
The configuration at phosphorus in cyclic (S)-HPMPC (1, cidofovir) and (S)-HPMPA (2) phenyl ester (5 and 6, respectively) diastereomers ((R(p))-5, (R(p))-6, (S(p))-6) was determined by X-ray crystallography and correlated to their (1)H and (31)P NMR spectra in solution. (R(p))-5 and (R(p))-6 have chair conformations with the nucleobase substituent equatorial and the P-OPh axial. Perhaps surprisingly, (S(p))-6 is (a, a) in the crystal and exists largely as an equilibrium of (a, a)/(e, e) conformers in chloroform or acetonitrile.
摘要
通过 X 射线晶体学确定了环状（S）-HPMPC（1，cidofovir）和（S）-HPMPA（2）苯酯（5 和 6，分别）非对映异构体（（R（p））-5、（R（p））-6、（S（p））-6）在磷上的构型，并将其与它们在溶液中的（1）H 和（31）P NMR 谱相关联。（R（p））-5 和（R（p））-6 具有椅式构象，碱基取代基处于平伏位置，而 P-OPh 处于轴向位置。也许令人惊讶的是，（S（p））-6 在晶体中为（a，a）构型，并且在氯仿或乙腈中主要以（a，a）/（e，e）构象的平衡形式存在。
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