Copper-catalyzed Enantioselective Allylic Substitution

The efficiency of organocopper reagents in the displacement of allylic leaving groups has been well established during the past five decades. In sharp contrast, catalytic asymmetric version of this reaction using a chiral catalyst is a more recent field of research. This chapter presents an overview of tremendous studies towards the development of an “ideally” active catalyst achieving high regio- and enantioselectivities. The comparative reactivity and generality of peptides, phosphorus, as well as N-heterocyclic carbenes based catalysts are discussed in the first part. Then, relevant scope and synthetic applications are reviewed. Noteworthily, this chapter is restricted to C–C bond formation processes, excluding C–B and C–Si bond formations

Cu-catalyzed enantioselective allylic alkylation with organolithium reagents

his protocol describes a method for the catalytic enantioselective synthesis of tertiary and quaternary carbon stereogenic centers, which are widely present in pharmaceutical and natural products. The method is based on the direct reaction between organolithium compounds, which are cheap, readily available and broadly used in chemical synthesis, and allylic electrophiles, using chiral copper catalysts. The methodology involves the asymmetric allylic alkylation (AAAAAAAAA) of allyl bromides, chlorides and ethers with organolithium compounds using catalyst systems based on Cu-Taniaphos and Cu-phosphoramidites. The protocol contains a complete description of the reaction setup, a method based on 1H-NMR, gas chromatography-mass spectrometry (GC-MS) and chiral HPLCPLCPLC for assaying the regioselectivity and enantioselectivity of the product, and isolation, purification and characterization procedures. Six Cu-catalyzed AAAAAAAAA reactions between different organolithium reagents and allylic systems are detailed in the text as representative examples of these procedures. These reactions proceed within 1-10 h, depending on the nature of the allylic substrate (bromide, chloride, or ether and disubstituted or trisubstituted) or the chiral ligand used (Taniaphos or phosphoramidite). However, the entire protocol, including workup and purification, generally requires an additional 4-7 h to complete

Mineral particles stimulate innate immunity through neutrophil extracellular traps containing HMGB1

Abstract Calcium phosphate-based mineralo-organic particles form spontaneously in the body and may represent precursors of ectopic calcification. We have shown earlier that these particles induce activation of caspase-1 and secretion of IL-1β by macrophages. However, whether the particles may produce other effects on immune cells is unclear. Here, we show that these particles induce the release of neutrophil extracellular traps (NETs) in a size-dependent manner by human neutrophils. Intracellular production of reactive oxygen species is required for particle-induced NET release by neutrophils. NETs contain the high-mobility group protein B1 (HMGB1), a DNA-binding protein capable of inducing secretion of TNF-α by a monocyte/macrophage cell line and primary macrophages. HMGB1 functions as a ligand of Toll-like receptors 2 and 4 on macrophages, leading to activation of the MyD88 pathway and TNF-α production. Furthermore, HMGB1 is critical to activate the particle-induced pro-inflammatory cascade in the peritoneum of mice. These results indicate that mineral particles promote pro-inflammatory responses by engaging neutrophils and macrophages via signaling of danger signals through NETs