Selective protection of 2′,2′-difluorodeoxycytidine (gemcitabine)
Selective protection of 2′,2′-difluorodeoxycytidine (gemcitabine)
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DOI：
10.1021/jo9911140
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发表时间：
1999-10-29
影响因子：
3.6
通讯作者：
Gallo, JM
中科院分区：
文献类型：
--
作者：
Guo, ZW;Gallo, JM
吉西他滨（1）是一种很有前途的新型抗胰腺癌药物。化合物1和其他细胞毒性剂选择性靶向实体瘤的改善可以通过缀合至靶向位于线粒体上并且已知在人脑肿瘤中过表达的外周苯并二氮杂卓受体（PBR）的配体来增强。此类化学缀合物的开发需要对化合物1的4-NH 2、5 '-OH和5'-OH进行选择性保护。所有三种单保护的和三种双保护的吉西他滨衍生物（2至7）通过采用单一常用的保护剂二叔丁基二甲基甲酰胺在不同条件下以良好的产率合成。因此，使用PER配体PK 11195以高产率合成了分别在4-NH 2、3 '-OH和5'-OH处偶联的三种单配体-吉西他滨缀合物（14至16）。这种选择性保护/脱保护策略提供了一种相对简单的修饰其他核苷的方法。
Gemcitabine (1) is a promising new anticancer agent used in pancreatic cancer. Improvement in the selective targeting of compound 1 and other cytotoxic agents to solid tumors may be enhanced by conjugation to ligands that target peripheral benzodiazepine receptors (PBRs) located on mitochondria and known to be overexpressed in human brain tumors. Development of such chemical conjugates requires selective protection on 4-NH2, 5'-OH, and 5'-OH of compound 1. All three monoprotected and three diprotected gemcitabine derivatives (2 to 7) were synthesized in good yield by employing a single commonly used protecting reagent, di-tert-butyl dicarbonate, under different conditions. Consequently, the three mono-ligand-gemcitabine conjugates coupled at 4-NH2, 3'-OH, and 5'-OH respectively (14 to 16) were synthesized in high yield using the PER ligand PK11195. This selective protection/deprotection strategy offers a relatively straightforward means to modify other nucleosides.