Polymer-assisted solution-phase synthesis of 2'-amido-2'-deoxyadenosine derivatives targeted at the NAD(+)-binding sites of parasite enzymes.
Polymer-assisted solution-phase synthesis of 2'-amido-2'-deoxyadenosine derivatives targeted at the NAD(+)-binding sites of parasite enzymes.
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聚合物辅助溶液相合成 2-酰胺基-2-脱氧腺苷衍生物，靶向寄生虫酶的 NAD( ) 结合位点。
DOI：
10.1021/cc0000343
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Link,A
中科院分区：
文献类型：
--
作者：
Golisade,A;Bressi,JC;VanCalenbergh,S;Gelb,MH;Link,A
A polymer-assisted solution-phase (PASP) synthesis of lead structure analogues ready for biological testing without the demand for chromatographic purification is described. Carboxylic acids are coupled to the Kenner or Ellman safety catch linker, respectively, activated by methylation or cyanomethylation and subsequently transferred to the 2‘-amino group of the 2‘-amino-2‘-deoxyadenosine scaffold (5). The chemoselective attack of weakly nucleophilic amino groups on the N-alkylatedN-acyl sulfonamide linker allows for the synthesis of amides6in high yields without the need for protection of primary and secondary hydroxyl functions. Thus, the use of 4-sulfamylbenzoylaminomethyl polystyrene is reported for the construction of chemoselective polymer-supported acylating reagents instead of its known use as linker in solid-phase peptide or organic synthesis. This approach is demonstrated to be well suited to obtain 2‘-amido-2‘-deoxyadenosine derivatives6in parallel format. Biological evaluation of all compounds reported revealed no improvement over known lead structures.
