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Third total synthesis of the meta, meta-bridged diarylheptanoid: myricanol with remarkable anti-tau properties.

In neurodegenerative diseases, such as Alzheimer´s disease, Huntington's disease, Parkinson's disease and multiple sclerosis, neuroinflammation induced by the microglial activation plays a crucial role. In effort to develop effective anti-neuroinflammatory compounds, different new linear polyoxygenated diarylheptanoids were synthesized. In LPS-triggered BV-2 microglial cells their ability to reduce the concentration of IL-6 and TNF-α pro-inflammatory cytokines was evaluated. Moreover, their effect on NF-κB and ATP citrate lyase (ACLY), a recently emerged target of metabolic reprogramming in inflammation, was assessed. Finally, we turn our attention to 2 inflammatory mediators derived from the cleavage of citrate catalyzed by ACLY: prostaglandin E2, nitric oxide and reactive oxygen species. All compounds showed null or minimal cytotoxicity; most of them had a great anti-neuroinflammatory activity. Diarylheptanoids 6b and 6c, bearing a halide atom and benzyl ether protective groups, exhibited the best effect since they blocked the secretion of all inflammatory mediators analyzed and reduced NF-κB and ATP citrate lyase protein levels.

Efficient Synthesis of 5-Nitro-benzo[b]furans via 2-Bromo-4-nitro-phenyl Acetates. -The conversion of 2-bromophenols into the target compounds is achieved via an acetylation/Sonogashira cross-coupling/cyclization sequence in one-pot. In the case of hydroxylated substrates (IV) and (VI), KOtBu is required for the cyclization of the intermediate acetylated cross-coupling products. -(BOCHICCHIO, A.; CHIUMMIENTO*, L.; FUNICELLO, M.; LOPARDO, M. T.; LUPATTELLI, P.;