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 Summary 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.

Recent Expedition in Pd‐ and Rh‐Catalyzed C(Ar)−B Bond Formations and Their Applications in Modern Organic Syntheses

“…The synthesis of Favolasins involves several key steps including the borylation reaction. In 2023, Banwell and co‐workers demonstrated a total synthesis of Favolasins A, E, G and K by the preparation of a key intermediate containing a boronate ester through a borylation of an aryl bromide (Scheme 26b) [104] …”

“…In 2023, Banwell and co-workers demonstrated a total synthesis of Favolasins A, E, G and K by the preparation of a key intermediate containing a boronate ester through a borylation of an aryl bromide (Scheme 26b). [104] The synthesis of Risdiplam, a potent oral splicing modifier for the treatment of spinal muscular atrophy (SMA), was reported by Ratni and Mueller using borylation as one of the key steps (Scheme 27a). [105] More recently, Medina and Giannerini presented a reaction protocol for preparing an RSV drug candidate by employing borylation as a viable pathway (Scheme 27b).…”