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

• Published in: European journal of medicinal chemistry 2013-09, Vol.67, p.384-389
• Main Authors: Vijai Kumar Reddy, T., Prabhavathi Devi, B.L.A., Prasad, R.B.N., Sujitha, P., Ganesh Kumar, C.
• Format: Article
• Language: English
• Subjects: 1-Aminoundecan-2-ol; Acetamides - chemical synthesis; Acetamides - chemistry; Acetamides - pharmacology; Alkanes - chemical synthesis; Alkanes - chemistry; Alkanes - pharmacology; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antimicrobial activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Azidolysis; Bacteria - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Clavaminol-G; Cytotoxic activity; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Epoxidation; Fungi - drug effects; HeLa Cells; Humans; MCF-7 Cells; Molecular Structure; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.07.001

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. [Display omitted] •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.