89Zr has a number of advantageous properties for PET-imaging, but optimal chelators for its widespread clinical application still need to be found. Tetrahydroxamates derived from the natural siderophore DFOB are promising candidates in this context. This study describes a solid-phase approach to isopeptide analogs of DFOB (termed ipDFO*) with four hydroxamate groups for stable Zr(IV)-chelation. The route uses either commercial or easily available Fmoc-protected precursors and allows the synthesis of ipDFO* and clickable AZA-ipDFO* derivatives in only a few hours. The solid-phase synthesis reduces the workload for the synthesis of ipDFO* and AZA-ipDFO* derivatives thus significantly compared to a previous multistep solution synthesis. The route is also modular and allows the synthesis of various ipDFO* derivatives with variation in the spacer length between the hydroxamate groups. This spacing is a critical parameter for finding the optimal chelator for hard metal cations like Zr(IV). It might thus help to speed up the search for an ideal Zr-chelator for PET-imaging and might also allow the extension to other metal cations of different size.

中文翻译：

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混合液相和固相合成异肽去铁胺类似物用于络合锆


89Zr 对于 PET 成像具有许多有利的特性，但仍需要找到适合其广泛临床应用的最佳螯合剂。源自天然铁载体 DFOB 的四羟肟酸酯是这方面有希望的候选者。本研究描述了一种固相方法，用于制备具有四个异羟肟酸基团的 DFOB 异肽类似物（称为 ipDFO*），以实现稳定的 Zr(IV) 螯合。该路线使用商业或容易获得的 Fm​​oc 保护前体，并允许在短短几个小时内合成 ipDFO* 和可点击的 AZA-ipDFO* 衍生物。与之前的多步溶液合成相比，固相合成显着减少了 ipDFO* 和 AZA-ipDFO* 衍生物合成的工作量。该路线也是模块化的，允许合成各种 ipDFO* 衍生物，并改变异羟肟酸基团之间的间隔长度。该间距是寻找 Zr(IV) 等硬金属阳离子最佳螯合剂的关键参数。因此，它可能有助于加快寻找用于 PET 成像的理想 Zr 螯合剂，并且还可能允许扩展到其他不同尺寸的金属阳离子。