Combinatorial Aid for Underprivileged Scaffolds: Solution and Solid-phase Strategies for a Rapid and Efficient Access To Novel Aza-diketopiperazines (Aza-DKP)

被引：20

作者：

Bonnet, Dominique ^{[1
]}

Margathe, Jean-Francois ^{[1
]}

Radford, Sally ^{[3
]}

Pflimlin, Elsa ^{[1
]}

Riche, Stephanie ^{[1
]}

Doman, Pete ^{[2
]}

Hibert, Marcel ^{[1
]}

Ganesan, A. ^{[4
]}

机构：

[1] Univ Strasbourg, CNRS, Fac Pharm, Lab Innovat Therapeut,UMR7200, F-67412 Illkirch Graffenstaden, France

[2] Maybridge, Tintagel PL34 OHW, Cornwall, England

[3] Univ Southampton, Sch Chem, Southampton SO17 1BJ, Hants, England

[4] Univ E Anglia, Sch Pharm, Norwich NR4 7TJ, Norfolk, England

来源：

ACS COMBINATORIAL SCIENCE | 2012年 / 14卷 / 05期

关键词：

aza-DKP; triazinedione; heterocycle; peptidomimetic; solid-phase synthesis; molecular diversity; BIOLOGICAL-ACTIVITY; CYCLOADDITION; ANTAGONISTS; 2,5-DIKETOPIPERAZINES; CHEMISTRY; PEPTIDE; LIBRARY; DESIGN; ESTERS; POTENT;

D O I：

10.1021/co300015k

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

An efficient solution-phase synthesis of aza-diketopiperazines (aza-DKP, triazinediones) is reported. A structurally diverse collection of c-[aza-alkylGly-Pro] derivatives and yet unreported 2,4,5-trisubstituted-1,2,4-triazine-3,6-diones has been synthesized starting from Fmoc-L-Pro-OH and various Fmoc-L-amino acids. To extend the practical value of this class of dipeptidomimetics, a general solid-phase synthesis approach amenable to library production was developed on both Wang-PS and HMBA-PS resins. The final acidic treatment of the resins in TFA/water mixture at room temperature enabled the rapid and quantitative cyclization/release highly pure triazinediones. The conformational preferences and the spatial organization of the three substituents of a representative 2,4,5-trisubstituted-1,2,4-triazine-3,6-dione were investigated by X-ray diffraction and H-1 NMR spectroscopy.

引用

页码：323 / 334

页数：12

共 37 条

[21] An investigation into the biological activity of the selected histidine-containing diketopiperazines cyclo(His-Phe) and cyclo(His-Tyr) [J].