Design and synthesis of novel leucomycin analogues modified at the C-3 position. Part II: 3-O-(3-Aryl-2-propenyl)leucomycin analogues.
The design and synthesis of 16-membered macrolides modified at the C-3 position are described. Starting from fully protected intermediate (5), appropriate modifications including Heck reaction were performed to furnish 3-O-(3-aryl-2-propenyl)leucomycin A(7) analogues (9a-9m). These leucomycin A(7) derivatives showed improved in vitro antibacterial activities against clinically important pathogens including erythromycin-resistant Streptococcus pneumoniae (ERSP). SAR analysis of derivatives modified at the C-3 and C-3'' positions suggested that single modification at C-3 or C-3'' was effective for in vitro antibacterial activity.
Furuuchi
Takeshi
T
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama 222-8567, Japan. takeshi_furuuchi@meiji.co.jp
Miura
Tomoaki
T
Kurihara
Ken-ichi
K
Yoshida
Takuji
T
Watanabe
Takashi
T
Ajito
Keiichi
K
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry; D018360:Crystallography, X-Ray; D015195:Drug Design; D015939:Kitasamycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015644:Miocamycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D013291:Streptococcus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D016227:Benzoquinones; D015939:Kitasamycin; C004532:quinone; D015644:Miocamycin; C033383:rokitamycin