National Institute for Chemical-Pharmaceutical Research and Development, Department of bioactive substances and pharmaceutical technologies, 112 Vitan Av., 031299 Bucharest-3, Romania.
Organic Chemistry Center "C.D.Nenitescu", Spectroscopy Laboratory, 202 B Splaiul Independentei, 060023 Bucharest, Romania.
Molecules. 2019 Jul 3;24(13):2446. doi: 10.3390/molecules24132446.
New 1'-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine () as nucleobases were synthesized by a selective Mitsunobu reaction on the primary hydroxymethyl group in the presence of 5-endo-hydroxyl group. Adenine and 6-substituted adenine homonucleosides were obtained by the substitution of the 6-chlorine atom of the key intermediate with ammonia and selected amines, and 6-methoxy- and 6-ethoxy substituted purine homonucleosides by reaction with the corresponding alkoxides. No derivatives appeared active against entero, yellow fever, chikungunya, and adeno type 1viruses. Two compounds ( and ) had lower IC (15 ± 2 and 21 ± 4 µM) and compound had an identical value of IC (28 ± 4 µM) to that of acyclovir, suggesting that the bicyclo[2.2.1]heptane skeleton could be further studied to find a candidate for sugar moiety of the nucleosides.
新型 1'-同碳核苷类似物，具有作为糖部分的手性取代双环[2.2.1]庚烷骨架。嘧啶类似物具有尿嘧啶、5-氟尿嘧啶、胸腺嘧啶和胞嘧啶，以及以 6-氯嘌呤（）为碱基的关键中间体，是在 5-endo-羟基存在下通过在伯羟甲基上的选择性 Mitsunobu 反应合成的。腺嘌呤和 6-取代腺嘌呤同核苷酸是通过用氨和选定的胺取代关键中间体的 6-氯原子得到的，而 6-甲氧基和 6-乙氧基取代嘌呤同核苷酸是通过与相应的烷氧基反应得到的。没有衍生物对肠、黄热病、基孔肯雅和腺病毒 1 型表现出活性。两种化合物（和）的 IC（15±2 和 21±4µM）较低，而化合物的 IC（28±4µM）与阿昔洛韦相同，这表明双环[2.2.1]庚烷骨架可以进一步研究，以找到核苷糖部分的候选物。
