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. Author manuscript; available in PMC: 2017 Aug 17.
Published in final edited form as: Nat Chem. 2016 Jul 25;8(11):1035–1041. doi: 10.1038/nchem.2577

Figure 1. Structures and retrosynthetic analysis of YM-254890, FR900359 and analogues.

Figure 1

a, Structures of the cyclic depsipeptides YM-254890 (1) and FR900359 (2), isolated from bacteria and plant, respectively, and the only compounds known to inhibit, both potently and selectively, Gq protein activation. In addition, structures of two hydrogenated analogues, YM-385780 (3) and YM-385781 (4), which are also inhibitors of the Gq protein, are shown. b, X-ray crystal structure (Protein Data Bank (PDB) 3AH8) of YM-254890 (1, cyan carbons) bound to a chimeric Gq/i protein (grey cartoon and surface) shows the hydrogen bonds between YM-254890 and the protein (yellow dotted lines). c, Retrosynthetic analysis of YM-254890 (1), which highlights key challenges in the synthesis: preparation of three key building blocks (in brown, blue and red), macrocyclization and generation of the N-MeDha moiety. PG, Protecting group; grey circles, solid support.