title: Synthesis and biological evaluation of kendomycin and its analogues.
abstract: Ansa compounds are gifts from microbes with intriguing molecular structures and highly potent bioactivities. One of the ansa compounds, kendomycin, has an oxa-metacyclophane skeleton with a quinone methide core and a fully substituted tetrahydropyran ring. Beyond a common synthetic strategy for construction of the ansa skeleton (i.e., elongation of an alkyl chain from an aromatic core followed by macrocyclization), we challenged a new method for construction of the ansa skeleton via simultaneous macrocyclization and benzannulation (using an intramolecular Dötz benzannulation). Understanding the reactivity of various Fischer-type ω-alkynyloxy chromium carbene complexes with kendomycin analogue syntheses led to achievement of the total synthesis of kendomycin. Investigations of structure-activity relationships revealed the need for an ansa skeleton for antimicrobial activity. Therefore, we envisage that this intramolecular Dötz benzannulation will enable divergent syntheses of ansa compounds which have important bioactive potential.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University , 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuyama
authors.forename: Masahito
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Fujimori
authors.forename: Kodai
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ozawa
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Sato
authors.forename: Yoko
authors.initials: Y
authors.lastname: Saikawa
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakata
mesh_terms: D056831:Coordination Complexes / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D011809:Quinones / Q000737:chemistry*; D017828:Rifabutin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D056831:Coordination Complexes; D047028:Macrocyclic Compounds; D011809:Quinones; C485395:kendomycin; D017828:Rifabutin; C030011:carbene; D008697:Methane