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 analo

详细信息	查看全文 | 推荐本文 |

• 作者：Tomoaki Miura ; Ken-ichi Kurihara ; Takeshi Furuuchi ; Takuji Yoshida ; Keiichi Ajito
• 关键词：16-Membered macrolide ; Midecamycin A₁ ; Miokamycin ; Streptococcus pneumoniae ; Antibacterial activity
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：1 April 2008
• 卷：16
• 期：7
• 页码：3985-4002
• 文件大小：897 K

摘要

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.