Department of Chemistry, South Kensington campus, Imperial College, London, UK SW7 2AZ.
Org Biomol Chem. 2011 Oct 7;9(19):6814-24. doi: 10.1039/c1ob05862b. Epub 2011 Aug 15.
Aspercyclide A (1) is a biaryl ether containing 11-membered macrocyclic natural product antagonist of the human IgE-FcεRI protein-protein interaction (PPI); a key interaction in the signal transduction pathway for allergic disorders such as asthma. Herein we report a novel approach to the synthesis of the C19 methyl ether of aspercyclide A, employing a Pd(0)-catalysed, fluorous-tagged alkenylgermane/arylbromide macrocyclisation (germyl-Stille reaction) as the key step, and evaluation of both enantiomers of this compound via ELISA following optical resolution by CSP-HPLC. A crystal structure for germyl hydride 27 is also reported.
Aspercyclide A（1）是一种含有 11 元大环的二芳基醚，是人类 IgE-FcεRI 蛋白-蛋白相互作用（PPI）的拮抗剂，该相互作用是哮喘等过敏疾病信号转导途径中的关键相互作用。本文报道了一种合成 Aspercyclide A 的 C19 甲基醚的新方法，该方法采用 Pd(0)催化的、含氟标记的烯基锗烷/芳基溴化物大环化（锗基-Stille 反应）作为关键步骤，并通过 CSP-HPLC 光学拆分后通过 ELISA 评估该化合物的两种对映异构体。还报道了锗基氢化物 27 的晶体结构。
