Knoevenagel-IMHDA and -IMSDA sequences for the synthesis of chiral condensed O,N-, S,N- and N-heterocycles.

Domino Knoevenagel-cyclization reactions of styrene substrates, containing an -(-formyl)aryl subunit, were carried out with -substituted 2-cyanoacetamides to prepare tetrahydro-4-pyrano[3,4-]quinolone and hexahydrobenzo[]phenanthridine derivatives by competing IMHDA and IMSDA cyclization, respectively. The diastereoselective IMHDA step with α,β-unsaturated amide, thioamide, ester and ketone subunits as a heterodiene produced condensed chiral tetrahydropyran or thiopyran derivatives, which in the case of Meldrum's acid were reacted further with amine nucleophiles in a multistep domino sequence. In order to simplify the benzene-condensed tricyclic core of the targets and get access to hexahydro-1-pyrano[3,4-]pyridine derivatives, a truncated substrate was reacted with cyclic and acyclic active methylene reagents in diastereoselective Knoevenagel-IMHDA reactions to prepare novel condensed heterocyclic scaffolds.

Hermansones A and B: Bioactive naphthazarin congeners from the European crust fungus Hermanssonia centrifuga.

Two previously undescribed naphthazarins named hermansones A (1) and B (2), were isolated from the wood-decaying basidiomycete Hermanssonia centrifuga. The study presents the first report of natural products from the species. The structures of the secondary metabolites were elucidated through NMR spectroscopy and mass spectrometry.

Aplospojaveedins A-C, unusual sulfur-containing alkaloids produced by the endophytic fungus using OSMAC strategy.

Three sulfur-containing alkaloids aplospojaveedins A-C (1-3) with a hitherto undescribed carbon skeleton comprising octahy-dronaphthalene, , -unsaturated lactam and glycine-cysteine moieties were isolated from . Their structures were elucidated by 1D and 2D NMR spectroscopy, HR-MS, X-ray diffraction analysis, DFT-NMR and TDDFT-ECD calculations. A plausible biosynthetic pathway and putative targets are described.

Targeting a key protein-protein interaction surface on mitogen-activated protein kinases by a precision-guided warhead scaffold.

For mitogen-activated protein kinases (MAPKs) a shallow surface-distinct from the substrate binding pocket-called the D(ocking)-groove governs partner protein binding. Screening of broad range of Michael acceptor compounds identified a double-activated, sterically crowded cyclohexenone moiety as a promising scaffold. We show that compounds bearing this structurally complex chiral warhead are able to target the conserved MAPK D-groove cysteine via reversible covalent modification and interfere with the protein-protein interactions of MAPKs.

VCD Analysis of Axial Chirality in Synthetic Stereoisomeric Biaryl-Type -Isochroman Heterodimers with Isolated Blocks of Central and Axial Chirality.

Optically active heterodimeric 5,5'-linked -isochromans, containing a stereogenic -trisubstituted biaryl axis and up to four chirality centers, were synthesized stereoselectively by using a Suzuki-Miyaura biaryl coupling reaction of optically active isochroman and 1-arylpropan-2-ol derivatives, providing the first access to synthetic biaryl-type isochroman dimers. Enantiomeric pairs and stereoisomers up to seven derivatives were prepared with four different substitution patterns, which enabled us to test how OR, ECD, and VCD measurements and DFT calculations can be used to determine parallel central and axial chirality elements in three isolated blocks of chirality. In contrast to natural penicisteckins A-D and related biaryls, the ECD spectra and OR data of (a) and (a) atropodiastereomers did not reflect the opposite axial chirality, but they were characteristic of the central chirality.