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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. [ABSTRACT FROM AUTHOR]

Antigens incorporated in subunit vaccines are typically poorly immunogenic, so a strong immunostimulant (adjuvant) and/or delivery system is required to boost immunogenicity. In this work, the various functional polymer nanostructures, that is, rods, worms, spheres, and tadpoles are used to develop potent peptide antigen delivery systems. The antigen PADRE-J8 (PJ8), derived from Group A Streptococcus (GAS) M-protein, is either physically mixed or chemically conjugated to polymeric nanoparticles of different shapes. The physical mixture of polymeric nanoparticles and antigen is more effective in inducing antibody production than their chemical conjugates. Moreover, rod-shaped polymeric nanoparticles in physical mixture with PJ8 elicited higher and more opsonic antibody titers than powerful complete Freund's adjuvant (CFA)-adjuvanted antigen. Herein, for the first time it is demonstrated that a) the block copolymer, in nanoparticle form, can act as an immune adjuvant, b) nanoparticle shape plays a crucial role in their immunogenicity, and c) antigen conjugation is not required, nor is antigen encapsulation or absorption. [ABSTRACT FROM AUTHOR]

1. Inducible defences are ubiquitous in the animal kingdom, but little is known about facultative changes in chemical defences in response to predators, especially so in vertebrates. 2. We tested for predator‐induced changes in toxin production of larval common toads (Bufo bufo), which are known to synthesize bufadienolide compounds. 3. The experiment included larvae originating from three permanent and three temporary ponds reared in the presence or absence of chemical cues of three predators: dragonfly larvae, newts or fish. 4. Tadpoles raised with chemical cues of predation risk produced higher numbers of bufadienolide compounds and larger total bufadienolide quantities than predator‐naive conspecifics. Further, the increase in intensity of chemical defence was greatest in response to fish, weakest to newts and intermediate to dragonfly larvae. Tadpoles originating from temporary and permanent ponds did not differ in their baseline toxin content or in the magnitude of their induced chemical responses. 5. These results provide the first compelling evidence for predator‐induced changes in chemical defence of a vertebrate that may have evolved to enhance survival under predation risk. [ABSTRACT FROM AUTHOR]

From the deep: The title actinomycete yielded three new abyssomicins J–L. The dimeric thioether J (see scheme) represents a unique example of a masked Michael acceptor with anti‐TB properties. Mechanistic insights into the biosynthesis, biomimetic synthesis, stability, and biological mechanism of action of abyssomicins aid our understanding of, and prospects for the development of Michael‐acceptor‐based drugs. [ABSTRACT FROM AUTHOR]

Chemical analysis of a Didemnum sp. (CMB-01656) collected during scientific Scuba operations off Wasp Island, New South Wales, yielded five new lamellarins A1 ( 1), A2 ( 2), A3 ( 3), A4 ( 4) and A5 ( 5) and eight known lamellarins C ( 6), E ( 7), K ( 8), M ( 9), S ( 10), T ( 11), X ( 12) and χ ( 13). Analysis of a second Didemnum sp. (CMB-02127) collected during scientific trawling operations along the Northern Rottnest Shelf, Western Australia, yielded the new lamellarin A6 ( 14) and two known lamellarins G ( 15) and Z ( 16). Structures were assigned to 1- 16 on the basis of detailed spectroscopic analysis with comparison to literature data and authentic samples. Access to this unique library of natural lamellarins ( 1- 16) provided a rare opportunity for structure-activity relationship (SAR) investigations, probing interactions between lamellarins and the ABC transporter efflux pump P-glycoprotein (P-gp) with a view to reversing multidrug resistance in a human colon cancer cell line (SW620 Ad300). These SAR studies, which were expanded to include the permethylated lamellarin derivative ( 17) and a series of lamellarin-inspired synthetic coumarins ( 19- 24) and isoquinolines ( 25- 26), successfully revealed 17 as a promising new non-cytotoxic P-gp inhibitor pharmacophore. [ABSTRACT FROM AUTHOR]

The sydowiols A (Ia) and C (Ic) are identified as M. [ABSTRACT FROM AUTHOR]

The rare marine sesterterpenes (-)-ircinianin (Ia) and (-)-ircinianin sulfate (Ib), along with the new biosynthetically related metabolites (-)-ircinianin lactam A (Ic), (-)-ircinianin lactam A sulfate (Id), (-)-oxoircinianin (IIa), (-)-oxoircinianin lactam A (IIb) and (-)-ircinianin lactone A (Ie) are presented. [ABSTRACT FROM AUTHOR]