Hybrid polarizing solids for pure hyperpolarized liquids through dissolution dynamic nuclear polarization.

Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) usually involves saturating the ESR transitions of polarizing agents (PAs; e.g., persistent radicals embedded in frozen glassy matrices). This approach has shown enormous potential to achieve greatly enhanced nuclear spin polarization, but the presence of PAs and/or glassing agents in the sample after dissolution can raise concerns for in vivo MRI applications, such as perturbing molecular interactions, and may induce the erosion of hyperpolarization in spectroscopy and MRI. We show that D-DNP can be performed efficiently with hybrid polarizing solids (HYPSOs) with 2,2,6,6-tetramethyl-piperidine-1-oxyl radicals incorporated in a mesostructured silica material and homogeneously distributed along its pore channels. The powder is wetted with a solution containing molecules of interest (for example, metabolites for MRS or MRI) to fill the pore channels (incipient wetness impregnation), and DNP is performed at low temperatures in a very efficient manner. This approach allows high polarization without the need for glass-forming agents and is applicable to a broad range of substrates, including peptides and metabolites. During dissolution, HYPSO is physically retained by simple filtration in the cryostat of the DNP polarizer, and a pure hyperpolarized solution is collected within a few seconds. The resulting solution contains the pure substrate, is free from any paramagnetic or other pollutants, and is ready for in vivo infusion.

In situ phosphine oxide reduction: a catalytic Appel reaction.

Several important reactions in organic chemistry thrive on stoichiometric formation of phosphine oxides from phosphines. To avoid the resulting burden of waste and purification, cyclic phosphine oxides were evaluated for new catalytic reactions based on in situ regeneration. First, the ease of silane-mediated reduction of a range of cyclic phosphine oxides was explored. In addition, the compatibility of silanes with electrophilic halogen donors was determined for application in a catalytic Appel reaction based on in situ reduction of dibenzophosphole oxide. Under optimized conditions, alcohols were effectively converted to bromides or chlorides, thereby showing the relevance of new catalyst development and paving the way for broader application of organophosphorus catalysis by in situ reduction protocols.

Total synthesis and absolute stereochemistry of integric acid.

An efficient total synthesis of integric acid is described starting from the Wieland-Miescher ketone. Key steps involve a one-step orthogonal deprotection/protection strategy of a thioacetal/aldehyde and the selective oxidative cleavage of a prenyl group in the presence of two other unsaturated moieties. The synthesis of both C4' diastereoisomers of integric acid delivered unambiguous evidence for (S)-stereochemistry at the C4' position.

Organophosphorus catalysis to bypass phosphine oxide waste.

The conversion of oxygen-containing compounds is often achieved by the use of phosphorus reagents. The newly formed phosphine oxide bond delivers the enthalpic gain that drives reactions, such as the Wittig, Mitsunobu, and Appel reaction, to completion. However, phosphine oxides are recognized as undesirable waste products and in the past decade several methods have emerged that address this issue by in situ regeneration of the phosphorus reagent. This Minireview outlines the two distinct strategies and underpinning research that led to these advances. The potential of the emerging field of phosphorus catalysis in chemistry is shown and new developments that may stimulate further research are described.

Protective group-free synthesis of 3,4-dihydroxytetrahydrofurans from carbohydrates: formal total synthesis of sphydrofuran.

Carbohydrates are taking a more prominent role in chemistry as an environmentally benign chemical feedstock. However, major efforts are still required to convert unprotected carbohydrates into high-value building blocks. We have investigated the protective group-free Wittig reaction and subsequential acid catalyzed intramolecular cyclization of unprotected carbohydrates to obtain 3,4-dihydroxytetrafurans. In this process, we have found that, when using Lewis acids and poly-alcohol substrates, additional attention should always be given to the catalytic nature of the acid as it might involve its ligands instead of the metal. Furthermore, we illustrate the viability of the concept by a straightforward formal total synthesis of the natural product sphydrofuran from d-xylose.

Controlled disassembly of peptide amphiphile fibres.

In this paper, the introduction of both a methionine residue and a nitrobenzyl derivative as a labile linker between the peptide part and the hydrophobic alkyl chain of a peptide amphiphile are presented. These modifications are shown not to inhibit the formation of structured assemblies that analogous peptide amphiphiles lacking the linkers are able to form. Moreover, the introduction of either labile linker allows removal of the peptide amphiphile's stabilizing hydrophobic moieties to initiate a controlled disassembly of fibre aggregates. This is achieved by either treatment with CNBr or UV irradiation, respectively. These disassembly mechanisms could be the starting point for methodology that allows further manipulation of self-assembled peptide amphiphile architectures.