title: Novel 16-membered macrolides modified at C-12 and C-13 positions of midecamycin A1 and miokamycin. Part 1: Synthesis and evaluation of 12,13-carbamate and 12-arylalkylamino-13-hydroxy analogues.
abstract: Design and synthesis of 16-membered macrolides modified at the C-12 and 13 positions are described. The compounds we report here have an arylalkylamino group attached to the C-12 position of the macrolactone. Both types of derivatives, 12,13-cyclic carbamates and non-carbamate analogues, were synthesized via 12-amino-13-hydroxy intermediates derived from 12,13-epoxide that was prepared by selective epoxidation at the C-12 and C-13 positions. 4'-Hydroxyl analogues were also prepared by acidic hydrolysis of a neutral sugar. These compounds were evaluated for in vitro antibacterial activity against respiratory tract pathogens. Some of these analogues exhibited an improved activity compared with the corresponding parent compound.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Kaisha Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. tomoaki_miura@meiji.co.jp
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Miura
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kurihara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Furuuchi
authors.forename: Takuji
authors.initials: T
authors.lastname: Yoshida
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ajito
mesh_terms: D000478:Alkylation; D000586:Amination; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006900:Hydroxylation; D048628:Ketolides / Q000737:chemistry; D007933:Leucomycins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D050296:Microbial Viability / Q000187:drug effects; D015644:Miocamycin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure
chemical_list: D000900:Anti-Bacterial Agents; D002219:Carbamates; D048628:Ketolides; D007933:Leucomycins; D015644:Miocamycin; C026483:midecamycin