trans-1,2-Bis(3,5-dimethoxy­phen­yl)ethene

The title compound, C18H20O4, was prepared in high yield from 3,5-dimethoxy­styrene via a Ru-catalysed homo-olefin metathesis. Exclusive formation of the E-configurated isomer was observed. Inter­estingly, one symmetric unit contains two mol­ecules adopting an s-syn-anti and and an all-s-anti conformation

trans-Ethyl­enedi-p-phenyl­ene diacetate

The centrosymmetric title compound, C18H26O4, was prepared in high yield from 4-acetoxy­styrene via Ru-catalysed homo-olefin metathesis. Exclusive formation of the E-configurated isomer was observed. In the crystal, a strong C—H⋯π inter­molecular inter­action links the mol­ecules together

Total Synthesis of (2RS)-alpha-Tocopherol through Ni-Catalyzed 1,4-Addition to a Chromenone Intermediate

A novel strategy for the total synthesis of a-tocopherol (vitamin E) was elaborated on the basis of the conjugate addition of AlMe3 (as a methyl anion equivalent) to a 2-substituted chromenone. Starting from trimethylhydroquinone and (R,R)-hexahydrofarnesol, the required chromenone substrate was efficiently prepared in a short sequence exploiting a TiCl4-mediated Fries rearrangement and a KOtBu-induced Baker-Venkatamaran rearrangement. The envisioned key step, which sets up the quaternary center at C2, was performed in virtually quantitative yield through Ni-catalyzed conjugate addition of AlMe3. However, this transformation, which likely proceeds through a radical mechanism, could not be rendered stereoselective by means of chiral ligands. Nevertheless, the elaborated synthesis of (2RS,4'R,8'R)-alpha-tocopherol (2-ambo-alpha-tocopherol) is efficient and challenges the future development of suitable protocols for the asymmetric 1,4-addition

Hydrophenalene-Cr(CO)(3) complexes as anti-inflammatory agents based on specific inhibition of NOD2 signalling: a SAR study

Small molecules, which specifically inhibit NOD2 signalling, are of high interest in the search for new anti-inflammatory drugs. In this context, the previously discovered hydrophenalene-Cr(CO)(3) complex 1 was taken as a lead and new structural analogues were prepared by means of chemical synthesis. The NOD2-inhibiting activity of the compounds was determined with cell-based reporter assays employing human embryonic kidney cells. As a result of the study, some clear structure activity relationships (SARs) could be identified. The best compounds were active at low mu M concentration

Anti-inflammatory Arene-Chromium Complexes Acting as Specific Inhibitors of NOD2 Signalling

Inflammation is a hallmark of microbial infection in mammals and is the result of a pathogen-induced release of inflammatory effectors. In humans a variety of germ-line encoded receptors, so-called pattern-recognition receptors, respond to conserved signatures on invading pathogens, which results in the transcriptional activation of pro-inflammatory responses. Inflammation is often detrimental to the host and leads to tissue damage and/or systemic dysfunctions. Thus, specific inhibitors of these pathways are desirable for medical interventions. Herein we report on the synthesis and use of some chromium-containing compounds (arene-Cr(CO)(3) complexes) with a core structure related to anti-inflammatory diterpenes produced by the sea whip Pseudopterogorgia elisabethae. By using cell-based reporter assays we identified complexes with a potent inhibitory activity on tumour necrosis factor (TNF), Toll-like receptor (TLR), and nucleotide binding domain, leucine-rich repeat-containing receptor (NLR) pathways. Moreover, we found one complex to be a specific inhibitor of inflammatory responses mediated by the NLR protein NOD2, a pivotal innate immune receptor involved in bacterial recognition. Synthesis and characterisation of a set of derivatives of this substance revealed structural requirements for NOD2 specificity. Taken together, our studies suggest this type of arene-Cr(CO)(3) complex as a potential lead for the development of antiphlogistica and pharmacologically relevant NOD2 inhibitors