An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids
Alexander, B.W.; Bartfield, N.M.; Gupta, V.; Mercado, B.Q.; Del Campo, M.; Herzon, S.B. (2024). An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids. Science (Wash.) 383(6685): 849-854. https://dx.doi.org/10.1126/science.adl6163
In: Science (Washington). American Association for the Advancement of Science: New York, N.Y. ISSN 0036-8075; e-ISSN 1095-9203, more
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| Keywords |
Securiflustra securifrons (Pallas, 1766) [WoRMS]
Marine/Coastal |
| Authors | | Top |
- Alexander, B.W.
- Bartfield, N.M.
- Gupta, V.
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- Mercado, B.Q.
- Del Campo, M.
- Herzon, S.B.
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| Abstract |
Securines and securamines are cytotoxic alkaloids that contain reactive alkene and heterocyclic residues embedded in skeletons comprising four to six oxidized rings. This structural complexity imparts a rich chemistry to the isolates but has impeded synthetic access to the structures in the nearly three decades since their isolation. We present a flexible route to eight isolates that exemplify the three skeletal classes of metabolites. The route proceeds by the modular assembly of the advanced azides 38 and 49 (13 steps, 6 to 10% yield), sequential oxidative photocyclizations, and late-stage functional group manipulations. With this approach, the targets were obtained in 17 to 19 steps, 12 to 13 purifications, and 0.5 to 3.5% overall yield. The structure of an advanced intermediate was elucidated by microcrystal electron diffraction (MicroED) analysis. The route will support structure-function and target identification studies of the securamines. |
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