Semi-synthetic preparation of the rare, cytotoxic, deep-sea sourced sponge metabolites discorhabdins P and U

• Published in: Bioorganic & medicinal chemistry letters 2006-04, Vol.16 (7), p.1944-1946
• Main Authors: Grkovic, Tanja, Kaur, Balwinder, Webb, Victoria L., Copp, Brent R.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Chemistry; Cytotoxic; Discorhabdin; Drug Screening Assays, Antitumor; Exact sciences and technology; General pharmacology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Latrunculia; Leukemia P388 - pathology; Marine alkaloid; Medical sciences; Mice; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Organic chemistry; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Porifera; Preparations and properties; Pyrroles - chemical synthesis; Pyrroles - chemistry; Quinones - chemical synthesis; Quinones - chemistry; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Thiazepines - chemical synthesis; Thiazepines - chemistry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.12.081

Semi-synthetic routes to the enzyme inhibitory and potently anti-proliferative marine natural products discorhabdins P and U were developed by one-step methylation reactions of discorhabdins C and B, respectively. Two novel semi-synthetic derivatives of discorhabdin U were also prepared, one of which ( 6) exhibited significant anti-proliferative activity. Semi-synthetic routes to the enzyme inhibitory and potently anti-proliferative marine natural products discorhabdins P and U were developed by one-step methylation reactions of discorhabdins C and B, respectively. Two novel semi-synthetic derivatives of discorhabdin U were also prepared, one of which ( 6) exhibited significant anti-proliferative activity.