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: Talia R Pettigrew, Rachel J Porter, Stephen J Walsh, Michael P Housden, Nelson Y S Lam, Jason S Carroll, Jeremy S Parker, David R Spring, Ian Paterson
• Journal: Chemical communications (Cambridge, England) (Chem Commun (Camb)) Vol. 56 Issue 10 Pg. 1529-1532 (Feb 04 2020) ISSN: 1364-548X [Electronic] England
• PMID: 31922172 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Macrolides
• aplyronine C
• aplyronine D
• aplyronine A

Topics

• Antineoplastic Agents (chemical synthesis)
• Cell Proliferation (drug effects)
• HeLa Cells
• Humans
• Macrolides (chemistry, pharmacology)
• Molecular Conformation
• Stereoisomerism
• Structure-Activity Relationship