Bio-inspired formal synthesis of hirsutellones A-C featuring an electrophilic cyclization triggered by remote Lewis
Xu-Wen Li1, Alexandre Ear, Lukas Roger
1Muséum National d'Histoire Naturelle, 57 rue Cuvier (CP 54), 75005 Paris (France); CNRS, UMR 7245, Unité Molécules de Communication et Adaptation des Micro-organismes, Paris (France).
Abstract:
A bio-inspired strategy was used to complete the formal synthesis of the antitubercular hirsutellone B and congeners A and C, through construction of its decahydrofluorene core from a linear polyene strand activated at both ends by a silyl enol ether and an allyl acetate. Our synthesis features a key electrophilic cyclization, starting with the remote activation (by [Yb(OTf)3] or BF3·OEt2) of the allyl acetate and stereoselectively affording the C ring. This was followed by an intramolecular Diels-Alder reaction to get the tricyclic core of the natural product. The stereoselective reduction of the resulting ketone towards the formal intermediate was critical to the success of this strategy.
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