Covering: up to early 2016Marine sponges are widely known as a rich source of natural products, especially of polyketide origin, with a wealth of chemical diversity. Within this vast collection, peroxide and peroxide-derived secondary metabolites have attracted significant interest in the fields of natural product isolation and chemical synthesis for their structural distinction and promising in vitro antimicrobial and anticancer properties. In this review, peroxide and peroxide-derived polyketide metabolites isolated from marine sponges in the past 35 years are summarised. Efforts toward their synthesis are detailed with a focus on methods that utilise or attempt to elucidate the complex biosynthetic interrelationships of these compounds beyond enzymatic polyketide synthesis. Recent isolations, advances in synthetic methodology and theories of biogenesis are highlighted and critically evaluated.

Core-shell nanoparticles that exhibit superparamagnetic properties and stability as colloidal suspensions have been widely employed for medical imaging, diagnosis, and targeted drug delivery. These materials are engineered for spatial guidance using an external magnetic field and are capable of transporting therapeutic payloads such as clinical drugs and protein structures. They can be tagged with fluorescent dyes and quantum dots as spectroscopic markers; and can generate an acute influx of heat when exposed to an alternating magnetic field. When these functions are used in combination, core-shell nanoparticles can operate in a multimodal fashion, on demand, using external and non-invasive stimuli. In this short review, selected examples of externally induced drug release systems with magnetic nanoparticle carriers are highlighted. This new and emerging field of nanomedicine has enormous potential to advance our therapeutic capabilities with a central concept of targeting, locating, and detonating diseased and cancerous tissues in vivo with precise ex vivo control.

An improved scalable synthesis of orthogonally functionalized methoxyaspartate, the chiral hinge region element in cystobactamids, is reported. This improvement sets the stage for the total synthesis of four new cystobactamids along with cystobactamid 861-2, whose antibacterial properties are determined and compared. The cyano derivative of cystobactamide 861-2 shows superior antibacterial activity against Gram-negative bacteria to any natural cystobactamide tested so far.T he group of cystobactamids was reported by Muller et al. in 2014 as part of a search for new secondary metabolites in Cystobacter sp. Cbv34. The extracts inhibited the growth of several Gram-negative and Gram-positive bacteria, and HPLCassisted bioactivity-guided screenings provided cystobactamids 919-1 (1) and 919-2 (2) as active compounds (Figure 1). 1 These oligoamides contain p-aminobenzoic acid building blocks and either an iso-β-methoxyasparagine or a β-methoxyasparagine unit. Later additional derivatives such as the cystobactamids 920-1 (3), 920-2 (4), and 862-1 (5) were reported that structurally differ in the D-and E-rings and the hinge region. 2 To date cystobactamid 862-1 is the most active natural member inhibiting several clinically relevant Gram-positive and Gramnegative strains (Acinetobacter baumannii: MIC = 0.5 μg/mL, Citrobacter f reundii: MIC = 0.06 μg/mL, carbapenem-resistant E. coli WT-III marRΔ74bp: MIC = 0.5 μg/mL, carbapenemresistant P. aeruginosa CRE: MIC = 1.0 μg/mL and Proteus vulgaris: MIC = 0.25 μg/mL) 2 by inhibiting bacterial type IIa topoisomerases. To date, three total syntheses of cystobactamids 861-2, 919-2, and 920-1 have been published by the Trauner group and by us. 2,3 These endeavors were essential to revise and

Figure 1. Cystobactamid natural products, synthetic epimer 3a and the structural revision of cystobactamids 920-1 and 920-2 as presented in this work (the related peptide albicidin is also shown).Letter pubs.acs.org/OrgLett