Total Synthesis of Kibdelomycin. (6th July 2022)

• Record Type: Journal Article
• Authors: He, Chi; Wang, Yu; Bi, Cheng; Peters, David S.; Gallagher, Timothy J.; Teske, Johannes; Chen, Jason S.; Corsetti, Rachel; D'Onofrio, Anthony; Lewis, Kim; Baran, Phil S.
• Is Part Of: Angewandte Chemie. Volume 134:Number 32(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-06
• Subjects: Antibiotics -- Glycosidation -- Modular Synthesis -- Total Synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202206183
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: A modular total synthesis of kibdelomycin is disclosed that should enable structure–activity relationship (SAR) studies of this interesting class of antibiotics. The route uses simple building blocks and addresses lingering questions about its structural assignment and relationship to amycolamicin, a recently described natural product reported to have a similar structure. Initial antibacterial assays reveal that both C‐22 epimers (the N ‐glycosidic linkage) of the natural product have similar activity while structurally truncated analogs lose activity. Abstract : A convergent synthesis of kibdelomycin, which leveraged readily available starting materials, enabled the efficient preparation of the potent antimicrobial and its C‐22 epimer in 16 steps (LLS). The modularity of the strategy provided rapid access to 8 analogs, allowing investigation of structural activity relation.