: 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 α-hydroxy-β-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; Amin, Hawraz Ibrahim M; Chianese, Giuseppina; Minassi, Alberto; Reddell, Paul W; Gaeta, Simone; Taglialatela-Scafati, Orazio; Appendino, Giovanni. - In: JOURNAL OF NATURAL PRODUCTS. - ISSN 1520-6025. - 86:12(2023), pp. 2685-2690. [10.1021/acs.jnatprod.3c00834]
Novel Skeletal Rearrangements of the Tigliane Diterpenoid Core
Chianese, GiuseppinaMembro del Collaboration Group
;Taglialatela-Scafati, Orazio
Penultimo
Supervision
;
2023
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 α-hydroxy-β-diketone system to trigger complex skeletal rearrangements and pave the way to new areas of the natural products chemical space.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.