Total synthesis and biological evaluation of clavaminol-G and its analogs

• First total synthesis of clavaminol-G (1) and 1-aminoundecan-2-ol (2).
• Synthesized derivatives of 2 with COOCH3 (3), COOH (4) and OH (5) functional groups.
• All compounds (1–5) were evaluated for cytotoxic and antimicrobial activities.
• 1-Aminoundecan-2-ol (2) exhibited promising cytotoxic and antimicrobial activities.

The first total synthesis of clavaminol-G (1) and 1-aminoundecan-2-ol (2) has been achieved from 10-undecenoic acid using epoxidation, regioselective azidolysis and in situ detosylation and reduction reactions as key steps. The methodology is extended for the synthesis of 1-aminoundecan-2-ol derivatives; namely, methyl 11-amino-10-hydroxyundecanoate (3), 11-amino-10-hydroxyundecanoic acid (4) and 11-aminoundecan-1,10-diol (5). Among these, 1-aminoundecan-2-ol (2) exhibited good antimicrobial activity and promising cytotoxicity towards HeLa, MDA-MB-231, MCF-7 and A549 cell lines with IC50 values of 4.36, 4.02, 3.88 and 6.78 μM, respectively. Compound 3 exhibited good activity against HeLa cells (IC50 = 3.59 μM), while compound 5 showed moderate activity towards HeLa and A549 cell lines. Clavaminol G (1) and compound 4 showed no activity towards all the cell lines.

The total synthesis of clavaminol-G (1) and its derivatives was accomplished for the first time from 10-undecenoic acid (6) and they were further evaluated for cytotoxic and antimicrobial activities.Figure optionsDownload as PowerPoint slide