Asymmetric Allylation by Chiral Organocatalyst-Promoted Formal Hetero-Ene Reactions of Alkylgold Intermediates.

An unprecedented catalytic asymmetric allylation of isatins and isatin-derived ketimines is reported enabled by a gold and chiral organocatalyst cooperative catalysis strategy. This method offers expeditious access to chiral 2,5-disubsituted alkylideneoxazolines containing vicinal stereogenic centers, mainly in optically pure form, and which are otherwise impossible to access. Mechanistic evidence reveals the presence of an alkylgold intermediate, and an X-ray crystal structure of the allylgold species illuminates its unique stability and reactivity. An asymmetric formal hetero-ene reaction of this gold intermediate, involving a dearomatization process, is enabled with assistance of a quinine-derived squaramide catalyst. This novel discovery extends the synthetic applications of gold complexes and the versatility of gold catalysis.

Gold-Catalyzed One-Pot Synthesis of Polyfluoroalkylated Oxazoles from N-Propargylamides Under Visible-Light Irradiation.

A gold-catalyzed synthesis of polyfluoroalkylated oxazoles from N-propargylamides under visible-light irradiation has been developed. These reactions display excellent compatibility of radicals and gold catalysts under visible-light irradiation. Mechanistic experiments indicate that polyfluoroalkyl iodides play a dual role in enhanced compatibility of radicals and gold catalysts through assisted protodeauration of vinyl gold and reactivated the gold catalyst. In addition, PPh3 AuNTf2 not only activates N-propargylamide to generate vinyl gold intermediate, but also greatly promotes homolysis of polyfluoroalkyl iodides under blue light irradiation.

Purification and functional characterization of the DUB domain of SdeA.

Intracellular pathogens like Legionella pneumophila hijack the host ubiquitination network in order to create a facultative niche for their survival by means of effector molecules secreted into the host cell. Some of these effectors function as ubiquitin ligases or deubiquitinases, among other types of enzymes. Deubiquitinating enzymes (DUBs) remove ubiquitin or ubiquitin-like modifiers from conjugated substrates to regulate various cellular processes. Members of the SidE effector family from the L. pneumophila pathogen harbor multiple functional domains that possess discrete biochemical activities impinging on host ubiquitin signaling. At the N-terminal end of these ~1500-residue proteins is a ~200-residue conserved DUB domain capable of recognizing both ubiquitin and the NEDD8 Ubl. SdeA, a member of the SidE family, plays an important role in intracellular bacterial replication. Downstream domains in this protein also catalyze substrate ubiquitination via a phosphoribosyl linkage. Several mammalian Rab proteins (Rab1, Rab30, and Rab33) have been shown to be targeted. The novel mechanism is independent of the classical E1 and E2 ubiquitin ligation machinery and does not require ATP. The N-terminal DUB domain, which does not appear to affect this ubiquitination activity, but it catalyzes cleavage of three different types of polyubiquitination chains (K11, K48, and K63) commonly found in host cells. This chapter describes methods, including purification of recombinant SdeA (full-length and DUB domain alone), and enzymatic assays that have been utilized to characterize the deubiquitination activity of SdeA.