Asymmetric hydrogenation of furans and benzofurans with iridium-pyridine-phosphinite catalysts.

Enantioselective hydrogenation of furans and benzofurans remains a challenging task. We report the hydrogenation of 2- and 3-substituted furans by using iridium catalysts that bear bicyclic pyridine-phosphinite ligands. Excellent enantioselectivities and high conversions were obtained for monosubstituted furans with a 3-alkyl or 3-aryl group. Furans substituted at the 2-position and 2,4-disubstituted furans proved to be more difficult substrates. The best results (80-97% conversion, 65-82% enantiomeric excess) were obtained with monosubstituted 2-alkylfurans and 2-[4-(trifluoromethyl)phenyl]furan. Benzofurans with an alkyl substituent at the 2- or 3-position also gave high conversions and enantioselectivity, whereas 2-aryl derivatives showed essentially no reactivity. The asymmetric hydrogenation of a 3-methylbenzofuran derivative was used as a key step in the formal total synthesis of the cytotoxic naphthoquinone natural product (-)-thespesone.

Hydrophobization of Monolithic Resorcinol-Formaldehyde Xerogels by Means of Silylation.

In materials research, the control of wettability is important for many applications. Since they are typically based on phenolics, organic aerogels, and xerogels are intrinsically hydrophilic in nature, and examples of the chemical functionalization of such gels are scarce and often limited to powders. This study reports on the silylation of monolithic resorcinol-formaldehyde (RF) xerogels using solutions of silyl chlorides and triflates, respectively, in combination with an amine base. The resulting gels are structurally characterized by means of elemental analysis, X-ray photoelectron spectroscopy, pycnometry, sorption analysis, and scanning electron microscopy with electron-dispersive X-ray spectroscopy. The wetting behavior of the silylated gels was studied by the determination of the contact angle to water after exposure of the gels to ambient air. Additionally, the uptake of liquid water and aqueous acids and bases was investigated. As a result, processes for the functionalization of RF xerogels with sterically demanding silyl moieties have been established. Although the analyses indicate that silylation occurred to a rather small extent, highly hydrophobic gels resulted which retained the wetting behavior over the course of several months with contact angles of >130°. Monoliths bearing sterically demanding silyl groups showed higher stability towards aqueous acid than trimethylsilylated RF gels.

Synthesis and structure-activity correlation of natural-product inspired cyclodepsipeptides stabilizing F-actin.

The fundamental role played by actin in the regulation of eukaryotic cell maintenance and motility renders it a primary target for small-molecule intervention. In this arena, a class of potent cytotoxic cyclodepsipeptide natural products has emerged over the last quarter-century to stimulate the fields of biology and chemistry with their unique actin-stabilizing properties and complex peptide-polyketide hybrid structures. Despite considerable research effort, a structural basis for the activity of these secondary metabolites remains elusive, not least for the lack of high-resolution structural data and a reliable synthetic route to diverse compound libraries. In response to this, an efficient solid-phase approach has been developed and successfully applied to the total synthesis of jasplakinolide and chondramide C and diverse analogues. The key macrocylization step was realized using ruthenium-catalyzed ring-closing metathesis (RCM) that in the course of a library synthesis produced discernible trends in metathesis reactivity and E/Z-selectivity. After optimization, the RCM step could be operated under mild conditions, a result that promises to facilitate the synthesis of more extensive analogue libraries for structure-function studies. The growth inhibitory effects of the synthesized compounds were quantified and structure-activity correlations established which appear to be in good alignment with relevant biological data from natural products. In this way a number of potent unnatural and simplified analogues have been found. Furthermore, potentially important stereochemical and structural components of a common pharmacophore have been identified and rationalized using molecular modeling. These data will guide in-depth mode-of-action studies, especially into the relationship between the cytotoxicity of these compounds and their actin-perturbing properties, and should inform the future design of simplified and functionalized actin stabilizers as well.

Solid-phase based total synthesis of Jasplakinolide by ring-closing metathesis.

The study of classical ring-closing metathesis and relay ring-closing metathesis in a total synthesis of Jasplakinolide and its desbromo analog is described.

Solid-phase based synthesis of jasplakinolide analogs by intramolecular azide-alkyne cycloadditions.

The synthesis of a focused library of jasplakinolide analogs with a 1,2,3-triazole in place of an E-configured double bond is described, featuring the Cu(I) catalyzed azide-alkyne cycloaddition reaction as an efficient macrocyclization tool.

When asymmetric aminocatalysis meets the vinylogy principle.

Over the past decade, asymmetric aminocatalysis has become a reliable synthetic platform for generating stereogenic centres at the α and ß positions of unmodified carbonyl compounds with very high fidelity. More recently, chemists have become interested in using aminocatalysis for targeting stereocentres even more remote from the catalyst's point of action. The key to success is the ability of the amine catalyst to propagate the electronic effects inherent to aminocatalytic reactivity modes (i.e. the HOMO-raising and the LUMO-lowering activating effects) through the conjugated π-system of poly-unsaturated carbonyls while transmitting the stereochemical information at distant positions. This feature article outlines how the combination of aminocatalysis with the principle of vinylogy has brought about the development of dienamine, trienamine, and vinylogous iminium ion activations, novel strategies for the asymmetric functionalisation of carbonyl compounds at their γ-, ε-, and δ-positions, respectively.