Total Syntheses of Favolasins A, E, G and K, Polyketides Isolated from Cultures of the Basidiomycetes Fungi Favolaschia sp. BCC 18686 and Favolaschia calocera BCC 36684

The structures assigned to all four members, 1-4, of the recently reported favolasin class of natural product have been prepared for the first time by chemical synthesis. Suzuki-Miyaura cross-coupling chemistry was used to establish the associated biaryl substructures. The key step used in preparing the 1,5-benzodioxepin ring system associated with compounds 3 and 4 was the acid-catalyzed 7-exo-tet cyclization of an appropriately substituted 2-(oxiran-2-ylmethoxy)phenol while a base-promoted 6-exo-tet cyclization of the same substrate was used to construct the 2,3-dihydrobenzo[b][1,4]dioxine core of target 2. The spectral data derived from the four synthetically-produced favolasins matched those reported for the corresponding natural products. Preliminary biological screening of compounds 1-3 as well as a suite of fourteen precursors reveal that they display no notable anti-bacterial, anti-fungal or anti-tumor activities but congener K (4) is active, in the mM range, against Plasmodium falciparum.