Synthesis and biological properties of the four optical isomers of 5-o-carboranyl-2',3'-didehydro-2',3'-dideoxyuridine.
Synthesis and biological properties of the four optical isomers of 5-o-carboranyl-2',3'-didehydro-2',3'-dideoxyuridine.
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5-邻碳硼基-2,3-二脱氢-2,3-二脱氧尿苷四种光学异构体的合成和生物学性质。
DOI：
10.1080/07328319808004670
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Schinazi,RF
中科院分区：
文献类型：
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作者：
Graciet,JC;Shi,J;Schinazi,RF
合成了5-O-碳硼烷基-2 ′，3 ′-双脱氧-2 ′，3 ′-双脱氧尿苷（d4 CU）的4个异构体，并测定了它们的抗病毒活性和对人正常细胞和癌细胞的细胞毒活性。甲硅烷基化的5-O-碳硼烷基尿嘧啶与受保护的D/L 2，3-二脱氧-2-苯基硒基核糖基乙酸酯的偶联在氧化消除和脱保护后提供所需化合物。尿嘧啶上缺电子的5-O-碳硼烷基部分的存在影响各种异构体的产率。一般而言，化合物在原代人淋巴细胞中表现出弱的抗人免疫缺陷病毒活性。对于各种光学异构体，没有注意到生物学特征的显著差异，这表明由碳硼烷基部分赋予的这些核苷的高亲脂性优先于2′，3 ′-二氢-2 ′，3 ′-二脱氧糖苷配基部分中的立体化学考虑。
The four isomers of the 5-o-carboranyl-2′,3′-didehydro-2′,3′-dideoxyuridine (d4CU) were synthesized and their antiviral activity and cytotoxicity in normal and cancer human cells determined. Coupling of silylated 5-o-carboranyluracil with the protected D/L 2,3-dideoxy-2-phenylselenenylribosylacetates provided after oxidative elimination and deprotection, the desired compounds. The presence of the electron deficient 5-o-carboranyl moiety on uracil influenced the yield of the various isomers. In general, the compounds demonstrated weak anti-human immunodeficiency virus activity in primary human lymphocytes. No marked difference in the biological profile was noted for the various optical isomers, suggesting that the high lipophilicity of these nucleosides imparted by the carboranyl moiety overrides stereochemical considerations in the 2′,3′-didehydro-2′,3′-dideoxy-aglycon moiety.