A facile and efficient protocol for the synthesis of sulfur substituted-cyclopyrophosphate of cIDPRE（P_S^1-cIDPRE） was developed.The key step was the cyclization process which was completed by the sulfur substituted cyclization precursor 1b via the one-pot phosphoramidite strategy.
Ren-Min WuNa QiYu-Wen JiaZhu GuanLiang-Ren ZhangLi-He ZhangZhen-Jun Yang
Deamination is a crucial step in the transformation of 6-cyclopropylamino guanosine prodrug to its active form. A convenient method using capillary electrophoresis （CE） without sample labeling was developed to analyze the deamination of a series of D-/L-6-cyclopropylamino guanosine analogs by mouse liver homogenate, mouse liver microsome, and adenosine deaminase （ADA）. A two-step process involving a 6-amino guanosine intermediate formed by oxidative N-dealkylation was demonstrated in the metabolism of 6-cyclopropylamino guanosine to 6-hydroxy guanosine. The results indicated that the transformation rates of different prodrugs to the active form varied greatly, which were closely correlated with the configuration of nucleosides and the structure of glycosyl groups. Most importantly, D-form analogs were metabolized much faster than their L-counterparts, thus clearly pointed out that compared to guanine, modification of glycosyl part might be a better choice for the development of L-Kuanosine analogs for the treatment of HIV,
Xin-Meng FanXian-Tao YangYu-Jia GuoRen-Min WuDe-Lin PanZhu GuanXiao-Mei LingLi-He ZhangZhen-Jun Yang
Three dinucleotides containing L-isonucleosides at 5＇-end were synthesized by an elegant phosphoramidite one-pot method. Their binding modes with HIV integrase were simulated and their anti-HIV activities in pseudotyped virus system were examined.
Linear diribonucleoside phosphotriester is an important intermediate for synthesizing biologically important compounds, such as cyclic bis（3＇-5＇） diguanylic acid （c-di-GMP） and its analogues. Atropisomerism of diastereomers generated by the chiral center of the P atom, which results in the doubling of signals in 31p NMR. The data of 31p NMR at different temperature are presented, and thereafter the reason is discussed.
Lu-Xin NaXu-Lin SunMeng WangKun-Feng LiLei XingZhuo ChenZhu GuanZhen-Jun Yang
