To investigate the role of the secondary 5-hydroxy group in the activity of the anticancer drug tigilanol tiglate (2b) (Stelfonta), oxidation of this epoxytigliane diterpenoid from the Australian rainforest plant Fontainea picrosperma was attempted. Eventually, 5-dehydrotigilanol tiglate (3a) proved too unstable to be characterized in terms of biological activity and, therefore, was not a suitable tool compound for bioactivity studies. On the other hand, a series of remarkable skeletal rearrangements associated with the presence of a 5-keto group were discovered during its synthesis, including a dismutative ring expansion of ring A and a mechanistically unprecedented dyotropic substituent swap around the C-4/C-10 bond. Taken together, these observations highlight the propensity of the alpha-hydroxy-beta-diketone system to trigger complex skeletal rearrangements and pave the way to new areas of the natural products chemical space.

Novel Skeletal Rearrangements of the Tigliane Diterpenoid Core

Maioli, Chiara;Minassi, Alberto;Gaeta, Simone;Appendino, Giovanni
2023-01-01

Abstract

To investigate the role of the secondary 5-hydroxy group in the activity of the anticancer drug tigilanol tiglate (2b) (Stelfonta), oxidation of this epoxytigliane diterpenoid from the Australian rainforest plant Fontainea picrosperma was attempted. Eventually, 5-dehydrotigilanol tiglate (3a) proved too unstable to be characterized in terms of biological activity and, therefore, was not a suitable tool compound for bioactivity studies. On the other hand, a series of remarkable skeletal rearrangements associated with the presence of a 5-keto group were discovered during its synthesis, including a dismutative ring expansion of ring A and a mechanistically unprecedented dyotropic substituent swap around the C-4/C-10 bond. Taken together, these observations highlight the propensity of the alpha-hydroxy-beta-diketone system to trigger complex skeletal rearrangements and pave the way to new areas of the natural products chemical space.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11579/177442
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