title: Total synthesis and stereochemistry revision of mannopeptimycin aglycone.
abstract: Development of efficient methods for preparation of bioactive nonribosomal peptides, containing densely functionalized nonproteinogenic amino acids, is an important task in organic synthesis. We have employed a concise synthesis for such amino acids by asymmetric aldol addition coupled with an isomeric resolution via diastereoselective cyclization. This approach is successfully applied to the first total synthesis of the cyclic hexapeptide aglycone of the mannopeptimycins, a group of glycopeptides known for potent activity against drug-resistant bacteria. The facile preparation of the key amino acids and the synthesis of the aglycone pave the way for further studies on this class of antibiotics and the development of new lead compounds with therapeutic potential. In addition, our studies have led to the revision of the stereochemistry of the β-methylphenylalanine residue in the mannopeptimycin aglycone.
authors: Department of Applied Chemistry, Tokyo Institute of Technology , Meguro-ku, Tokyo 152-8552, Japan.
authors: Shinichiro
authors: S
authors: Fuse
authors: Hirotsugu
authors: H
authors: Koinuma
authors: Atsushi
authors: A
authors: Kimbara
authors: Miho
authors: M
authors: Izumikawa
authors: Yuto
authors: Y
authors: Mifune
authors: Haiyin
authors: H
authors: He
authors: Kazuo
authors: K
authors: Shin-ya
authors: Takashi
authors: T
authors: Takahashi
authors: Takayuki
authors: T
authors: Doi
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; C478082:mannopeptimycin