Total synthesis and biological evaluation of simplified aplyronine analogues as synthetically tractable anticancer agents.
- Abstract:
- The aplyronines are a family of highly cytotoxic marine natural products with potential application in targeted cancer chemotherapy. To address the severe supply issue, function-oriented molecular editing of their macrolactone scaffold led to the design of a series of simplified aplyronine analogues. Enabled by a highly convergent aldol-based route, the total synthesis of four analogues was achieved, with a significant improvement in step economy versus previous compounds, and their cancer cell growth inhibition in the HeLa cell line was determined. The modular strategy presented offers a means for significantly shortening their chemical synthesis to facilitate the continued development of this promising class of anticancer agent.
- Authors:
- TR Pettigrew, RJ Porter, SJ Walsh, MP Housden, NYS Lam, JS Carroll, JS Parker, DR Spring, I Paterson
- Journal:
- Chem Commun (Camb)
- Citation info:
- 56(10):1529-1532
- Publication date:
- 4th Feb 2020
- Full text
- DOI