Synthesis of 20‐Membered Macrocyclic Pseudo‐Natural Products Yields Inducers of LC3 Lipidation
نویسندگان
چکیده
Design and synthesis of pseudo-natural products (PNPs) through recombination natural product (NP) fragments in unprecedented arrangements enables the discovery novel biologically relevant chemical matter. With a view to wider coverage NP-inspired biological space, we describe combination this principle with macrocycle formation. PNP-macrocycles were synthesized efficiently stereoselective one-pot procedure including 1,3-dipolar cycloadditions different dipolarophiles dimeric cinchona alkaloid-derived azomethine ylides formed situ. The 20-membered bis-cycloadducts embody 18 stereocenters an additional fragment-sized NP-structure. After further functionalization, collection 163 macrocyclic PNPs was obtained. Biological investigation revealed potent inducers lipidation microtubule associated protein 1 light chain 3 (LC3) protein, which plays prominent role various autophagy-related processes.
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ژورنال
عنوان ژورنال: Angewandte Chemie
سال: 2022
ISSN: ['1521-3773', '1433-7851', '0570-0833']
DOI: https://doi.org/10.1002/ange.202114328