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Updated: Dec 31, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Total synthesis and biological evaluation of simplified aplyronine analogues as synthetically tractable anticancer
Talia R Pettigrew1, Rachel J Porter1, Stephen J Walsh2
1University Chemical Laboratory, Lensfield Road, Cambridge, CB2 1EW, UK.
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.
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