title: Total Synthesis and Antimicrobial Activity of Chlorocatechelin A.
abstract: Chlorocatechelin A (1) is a structurally unique microbial siderophore containing two units of 4-chloro-2,3-dihydroxybenzoic acid (CDB) and a characteristic acylguanidine structure. Purification from the microbe culture is not an easy task due to the lability of the acylguanidine and its chelating nature. Here we report the first convergent total synthesis and antimicrobial activity of chlorocatechelin A (1). The bis-acylated arginine was constructed using a Schotten-Baumann reaction whereas the CDB component was synthesized from o-vanillin (8). Condensation with an ornithine derivative synthesized from 1-benzyl d-glutamate was followed by deprotection in basic and neutral conditions to complete the total synthesis. We examined the antimicrobial activity of chlorocatechelin A (1) and found that this siderophore was active against desferrioxamine B (DFB)-sensitive microbes including the fish pathogen Pasteurella piscicida.
authors.affiliation: †Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kishimoto
authors.affiliation: †Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishimura
authors.affiliation: ‡Institute of Microbial Chemistry (BIKAKEN), Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hatano
authors.affiliation: ‡Institute of Microbial Chemistry (BIKAKEN), Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Igarashi
authors.affiliation: †Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakeya
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001120:Arginine / Q000737:chemistry*; D003676:Deferoxamine / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005399:Fishes / Q000382:microbiology; D015394:Molecular Structure; D010325:Pasteurella / Q000187:drug effects / Q000472:pathogenicity; D017262:Siderophores / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004151:Dipeptides; D017262:Siderophores; C000596578:chlorocatechelin A; D001120:Arginine; D003676:Deferoxamine