A mild and efficient approach to the 6H-oxazolo[3,2-f]pyrimidine-5,7-dione scaffold via unexpected rearrangement of 2,3-dihydropyrimido[6,1-b][1,5,3]dioxazepine-7,9(5H,8H)-diones: synthesis, crystallographic studies, and cytotoxic activity screening

被引：8

作者：

Mieczkowski, Adam ^{[1
]}

Bazlekowa, Milena ^{[2
]}

Baginski, Maciej ^{[3
]}

Wojcik, Jacek ^{[1
]}

Winczura, Alicja ^{[1
]}

Miazga, Agnieszka ^{[1
]}

Ghahe, Somayeh Shahmoradi ^{[2
]}

Gajda, Roman ^{[4
]}

Wozniak, Krzysztof ^{[4
]}

Tudek, Barbara ^{[1
,2
]}

机构：

[1] Polish Acad Sci, Inst Biochem & Biophys, 5a,Pawinskiego St, PL-02106 Warsaw, Poland

[2] Univ Warsaw, Fac Biol, Inst Genet & Biotechnol, 5a,Pawinskiego St, PL-02106 Warsaw, Poland

[3] Univ Warsaw, Dept Chem, 1 Pasteura St, PL-02093 Warsaw, Poland

[4] Univ Warsaw, Dept Chem, Biol & Chem Res Ctr, 101 Zwirki & Wigury St, PL-02089 Warsaw, Poland

来源：

TETRAHEDRON LETTERS | 2016年 / 57卷 / 07期

关键词：

6,5 '-O-Anhydrouridines; Oxazolopyrimidines; Dioxazepine rearrangement; Ring contraction; Cytotoxicity; SOLID-SUPPORTED SYNTHESIS; N-(CHLOROCARBONYL) ISOCYANATE; 1,3-DIACID CHLORIDES; DERIVATIVES; TRACELESS; ANALOGS;

D O I：

10.1016/j.tetlet.2016.01.006

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

We report a mild and efficient approach to the optically pure 6H-oxazolo[3,2-f]pyrimidine-5,7-dione scaffold via the unexpected rearrangement and ring contraction of 2,3-dihydropyrimido[6,1-b][1,5,3]-dioxazepine-7,9(5H,8H)-diones derived from nucleoside precursors. The developed procedure enables the synthesis of a wide range of compounds with great structural diversity. The structure of the obtained compounds was confirmed by NMR spectroscopy and single crystal X-ray structural analysis. The final products were tested for cytotoxic effect on one non-cancerous (fibroblasts) and six cancer cell lines of different origins (colon, glioma, breast, cervix, vulvar, and lung). The synthesized products are low molecular weight compounds with lead-like properties suitable for a medicinal chemistry optimization program. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：743 / 746

页数：4

共 17 条

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