Harnessing the Intrinsic Reactivity within the Aplysinopsin Series for the Synthesis of Intricate Dimers: Natural from Start to Finish
Received: 13 April 2015
Accepted after revision: 11 June 2015
24 July 2015 (online)
Aplysinopsin monomers are considered as plausible biosynthetic precursors of the wider aplysinopsin family of marine alkaloids. The idea of harnessing their intrinsic reactivity to undertake the synthesis of dictazoles or cycloaplysinopsins logically emerged from this status. These biosynthetic considerations led us to the first total syntheses of dictazole B and other valuable cyclobutanes. When further exploiting pre-encoded reactivity, our first total synthesis of tubastrindole B originated from the ring-expansion cascade of its dictazole-type precursor. Moreover, the isolation of a transient biosynthetic intermediate combined with dimerization outcomes of a hydantoin-containing monomer allowed us to explain the formation of cycloaplysinopsins A and B.
2 Easy Access to Dictazole Cyclobutanes
3 Synthesis of Cycloaplysinopsins by Ring Expansion
4 Conclusion and Future Prospects
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Even during our early attempts of non-photochemical dimerization with Ledwith–Weitz salt, no dimeric entity was observed. For the use of Ledwith–Weitz salt in the total synthesis of kingianins via RCDA see:
Also, preliminary results of photoredox catalysis experiments carried out on monomers 1, 2, 8, and 9 with [Ru(bpy)3](PF6)2 under compatible conditions only led to E/Z isomerization of the starting materials without formation of any dimeric compound, but further investigations are still ongoing to test a questioned single electron transfer (SET) mechanism:
Inspired by previously reported ring expansion cascade of Baran and Wenkert respectively: