Total synthesis and biological evaluation of simplified aplyronine analogues as synthetically tractable anticancer agents.
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Pettigrew, Talia R
Porter, Rachel J
Walsh, Stephen J https://orcid.org/0000-0002-3164-1519
Housden, Michael P
Lam, Nelson YS https://orcid.org/0000-0002-9307-0619
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.
Description
Keywords
Antineoplastic Agents, Cell Proliferation, HeLa Cells, Humans, Macrolides, Molecular Conformation, Stereoisomerism, Structure-Activity Relationship
Journal Title
Chem Commun (Camb)
Conference Name
Journal ISSN
1359-7345
1364-548X
1364-548X
Volume Title
56
Publisher
Royal Society of Chemistry (RSC)
Publisher DOI
Rights
All rights reserved
Sponsorship
Engineering and Physical Sciences Research Council (1651727)