Synthesis of the C19 methyl ether of aspercyclide A viagermyl-Stille macrocyclisation and ELISA evaluation of both enantiomers following optical resolution?

Organic & Biomolecular Chemistry Pub Date: 2011-07-08 DOI: 10.1039/C1OB05862B

Abstract

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.

Graphical abstract: Synthesis of the C19 methyl ether of aspercyclide A viagermyl-Stille macrocyclisation and ELISA evaluation of both enantiomers following optical resolution
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