title: Total Synthesis of Mannopeptimycins α and β.
abstract: The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (L- and D-βhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. The D-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. Critically, a gold-catalyzed N-glycosylation of a D-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-βhEnd unit with excellent efficiency and stereoselectivity. The L-βMePhe unit was prepared using a Pd-catalyzed C-H arylation method. The L-βhEnd, D-Tyr(di-Man), and L-βMePhe units were prepared in gram quantities. A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β.
authors.affiliation: Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: Rui
authors.initials: R
authors.lastname: Jiao
authors.affiliation: Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, China.
authors.forename: Long
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Gang
authors.initials: G
authors.lastname: He
authors.affiliation: State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.|Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D006020:Glycopeptides / Q000138:chemical synthesis*; D019791:Guanidine / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; C478082:mannopeptimycin; D019791:Guanidine