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

Abstract

Comprehensive SummaryThe 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.