Synthesis and antibacterial activity of racemic paecilocin A and its derivatives against methicillin-sensitive and -resistant Staphylococcus aureus

• Published in: Tetrahedron letters Vol. 67; pp. 152888 - 152891
• Main Authors: Ibraheem, Walaa, Wils, Quentin, Camiade, Emilie, Ahmed, Elhadi, Thibonnet, Jérôme, Thiery, Emilie, Petrignet, Julien
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 16.03.2021; Elsevier
• Subjects: Antibacterial activity; Chemical Sciences; Chemistry; Chemistry, Organic; Halogen-metal exchange; Natural phthalide; Organic chemistry; Physical Sciences; Science & Technology; Antibacterial activity; Natural phthalide; Halogen-metal exchange; COROLLOSPORINE; DESIGN; METHODOLOGIES; ENDOPHYTIC FUNGUS; CHEMISTRY; CJ-12,954; METABOLITE; CYTOSPORONES; PHTHALIDE DERIVATIVES; CYCLIZATION
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2021.152888

[Display omitted] •A 4-steps racemic synthesis of a natural phthalide, the paecilocin A 1a.•Preparation of twelve analogues of paecilocin A.•Iodine-magnesium exchange promoted by iPrMgCl.LiCl as key-step.•Antibacterial activities against sensitive and resistant strains of Staphylococcus aureus of all compounds were evaluated.•1a and three analogs were found to be 4–32 times more active on MRSA compared to MSSA. A total synthesis in four steps of racemic paecilocin A, a natural marine phthalide is reported. The synthetic pathway includes an iodine-magnesium exchange followed by a condensation on an aldehyde and represents a sufficiently flexible approach to allow the synthesis of twelve analogs. The synthesized compounds were investigated for their antibacterial activity against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant strain (MRSA). Three analogs were found to have similar or better antibacterial activity than the natural compound on MRSA.