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.
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.
Miura
Tomoaki
T
Pharmaceutical Research Center, Meiji Seika Kaisha Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. tomoaki_miura@meiji.co.jp
Kurihara
Ken-ichi
K
Furuuchi
Takeshi
T
Yoshida
Takuji
T
Ajito
Keiichi
K
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
D000900:Anti-Bacterial Agents; D002219:Carbamates; D048628:Ketolides; D007933:Leucomycins; D015644:Miocamycin; C026483:midecamycin