Nucleic acid related compounds, part 115. Syntheses of puromycin from adenosine and 7-deazapuromycin from tubercidin, and biological comparisons of the 7-aza/deaza pair
Nucleic acid related compounds, part 115. Syntheses of puromycin from adenosine and 7-deazapuromycin from tubercidin, and biological comparisons of the 7-aza/deaza pair
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DOI：
10.1021/jo010935d
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发表时间：
2001-11-30
影响因子：
3.6
通讯作者：
Kaspar, RL
中科院分区：
文献类型：
--
作者：
Robins, MJ;Miles, RW;Kaspar, RL
用叔丁基二苯基甲硅烷基氯保护（O 5 ′）2 ′，3 ′-脱水腺苷，用溴化二甲基硼打开环氧化物，得到T-溴-X-脱氧木糖异构体，用苄基异氰酸酯处理，得到2 ′-O-（N-苄基氨基甲酰基）衍生物。闭环得到恶唑烷酮，连续脱保护得到3 '-氨基-3'-脱氧腺苷的有效途径。抗生素杀结核菌素{7-脱氮腺苷; 4-氨基-7-（β-D-呋喃核糖基）吡咯并[2，3-d]嘧啶}的类似处理得到3 ′-氨基-3 ′-脱氧杀结核菌素。X-氨基官能团的三氟乙酰化，用N，N '-双[（二甲氨基）亚甲基]肼将杂环氨基修饰成（1，2，4-三唑-4-基）环，并用二甲胺进行亲核芳族取代，得到嘌呤霉素氨基糖苷[9-（3-氨基-3-脱氧-β-D-呋喃核糖基）-6-（二甲氨基）嘌呤]及其7-脱氮类似物。氨酰化[BOC-（4-甲氧基-L-苯丙氨酸）]和脱保护得到嘌呤霉素和7-脱氮嘌呤霉素。大多数反应在环境温度或低于环境温度下得到高产率。用7-aza/deaza对观察到兔网织红细胞系统中蛋白质生物合成的等效抑制和几种细菌的平行生长抑制。嘌呤霉素嘌呤环上的N7被“CH”取代对生物活性没有明显影响。
Protection (O5') of 2',3'-anhydroadenosine with tert-butyldiphenylsilyl chloride and epoxide opening with dimethylboron bromide gave the T-bromo-X-deoxy xylo isomer which was treated with benzylisocyanate to give the 2'-O-(N-benzylcarbamoyl) derivative. Ring closure gave the oxazolidinone, and successive deprotection concluded an efficient route to 3'-amino-3'-deoxyadenosine. Analogous treatment of the antibiotic tubercidin {7-deazaadenosine; 4-amino-7-(beta -D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine} gave 3'-amino-3'-deoxytubercidin. Trifluoroacetylation of the X-amino function, elaboration of the heterocyclic amino group into a (1,2,4-triazol-4-yl) ring with N,N'-bis[(dimethylamino)methylene]hydrazine, and nucleophilic aromatic substitution with dimethylamine gave puromycin aminonucleoside [9-(3-amino-3-deoxy-beta -D-ribofuranosyl)-6-(dimethylamino)purine] and its 7-deaza analogue. Aminoacylation [BOC-(4-methoxy-L-phenylalanine)] and deprotection gave puromycin and 7-deazapuromycin. Most reactions gave high yields at or below ambient temperature. Equivalent inhibition of protein biosynthesis in a rabbit reticulocyte system and parallel growth inhibition of several bacteria were observed with the 7-aza/deaza pair. Replacement of N7 in the purine ring of puromycin by "CH" has no apparent effect on biological activity.