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.

Peptide-based subunit vaccines include only minimal antigenic determinants, and, therefore, are less likely to induce allergic immune responses and adverse effects compared to traditional vaccines. However, peptides are weakly immunogenic and susceptible to enzymatic degradation when administered on their own. Hence, we designed polyelectrolyte complex (PEC)-based delivery systems to protect peptide antigens from degradation and improve immunogenicity. Lipopeptide (LCP-1) bearing J8 B-cell epitope derived from Group A Streptococcus (GAS) M-protein was selected as the model peptide antigen. In the pilot study, LCP-1 incorporated in alginate/cross-linked polyarginine-J8-based PEC induced high J8-specific IgG antibody titres. The PEC system was then further modified to improve its immune stimulating capability. Of the formulations tested, PEC-4, bearing LCP-1, alginate and cross-linked polylysine, induced the highest antibody titres in BALB/c mice following subcutaneous immunisation. The antibodies produced were more opsonic than those induced by mice immunised with other PECs, and as opsonic as those induced by antigen adjuvanted with powerful complete Freund’s adjuvant.