We present a high-resolution 19F NMR platform for the enantiodifferentiation of chiral hydroxy acids via a rapid three-component derivatization reaction between a 19F-labeled chiral amine,2-formylphenylboronic acid,and the hydroxy acid analyte. The probe design includes two different fluorinated groups (-CF3 and -OCF3),allowing for detection using dual-site 19F readout. This dual-fluorine strategy markedly improves chiral resolution and minimizes signal overlap,a common limitation of conventional 1H NMR approaches. The method simultaneously distinguishes up to ten chiral hydroxy acids within a single spectrum and allows accurate determination of enantiomeric excess,offering a versatile,efficient,and separation-free platform for the rapid chiral analysis of structurally diverse hydroxy acids.

Macroautophagy maintains cellular and organismal homeostasis,and entails de novo synthesis of double-membrane autophagosome. The effective formation of autophagosome requires the recruitment of the ATG12 similar to ATG5-ATG16L1 complex to the pre-autophagosomal structure by relevant ATG16L1-binding autophagic factors including FIP200. However, the molecular mechanism governing the specific interaction of ATG16L1 with FIP200 remains elusive. Here, we uncover that ATG16L1 contains a FIP200-interacting region (FIR), which not only can directly bind FIP200 Claw domain, but also can serve as an atypical ATG8-interacting motif to selectively recognize mammalian ATG8 family proteins (ATG8s). We determine the high-resolution crystal structures of ATG16L1 FIR in complex with FIP200 Claw and GABARAPL1, respectively, and elucidate the molecular mechanism underlying the interactions of ATG16L1 with FIP200 and ATG8s. To distinguish the precise contribution of FIP200 from ATG8s for binding to ATG16L1 FIR in autophagy, we develop a ATG16L1 mutant that can exclusively interact with ATG8s but not FIP200. Finally, using relevant cell-based functional assays, we demonstrate that the interaction of ATG16L1 with FIP200 is indispensable for the effective autophagic flux. In conclusion, our findings provide mechanistic insights into the interactions of ATG16L1 with FIP200 and ATG8s, and are valuable for further understanding the function of ATG16L1 in autophagy.

Here,we present an efficient electroenzymatic strategy for transforming allyl alcohols into chiral alkyl aldehydes with excellent enantioselectivity. Adverse interactions between the two are effectively prevented by employing a biphasic system to physically separate the anode from the enzymes. Furthermore, using the redox mediator 2,2,6,6-tetramethyl-1-piperinedinyloxy (TEMPO) significantly lowers the overpotential and enhances the efficiency of the allyl alcohol electrooxidation step. The ene-reductase OYE1 is employed to catalyze the reduction of the resulting E-alkenes, typically yielding chiral alkyl aldehyde. Additionally, the ene-reductase GluER-T36A is capable of reducing both E- and Z-alkenes, yielding chiral alkyl aldehyde with the same configuration. This electroenzymatic system is characterized by outstanding yields (up to 93%) and excellent stereoselectivity (>99% enantiomeric excess, ee). Molecular docking provides a detailed understanding of the internal mechanism of GluER-T36A. This study introduces a complementary approach to traditional transition-metal-catalyzed methods,where the transformation of E- and Z-allylic alcohols typically results in products with opposite stereochemical configurations.

Comprehensive Summary The pentafluorosulfanyl (SF5) group,characterized by its high electronegativity,lipophilicity and unique octahedral geometry,has the potential to modify the physicochemical properties of both pharmaceuticals and agrochemicals. Recently,pentafluorosulfanyl-containing compounds have garnered increasing attention,and big progress has been made in the development of novel synthetic strategies for these compounds. Central to these advancements is the exploration of synthesis and novel reaction of radical pentafluorosulfanylation reagents. This account provides an overview of the gas-reagent-free practical synthesis and new reaction of pentafluorosulfanyl chloride (SF5Cl) developed by our group.Key Scientists of SF5 Chemistry A partial list of the key scientists'main contributions to the development of pentafluorosulfanyl chemistry

Hygromycin A, a once-forgotten antibiotic first isolated in 1953, is recently rediscovered as a novel inhibitor of Lyme disease caused by Borrelia burgdorferi. Given the increasing resistance of gut microbes to antibiotic treatments, there is an urgent need for new therapies with novel mechanisms of action. The molecular architecture of hygromycin A, characterized by its fragmented structure, makes it an appealing platform for derivatization. In this study, it develops a latent functionality strategy to introduce the beta-hydroxy ketone motif into the sugar fragment via the 1,3-dipolar cycloaddition of furan. The facile epimerization at the C5 position enables a rapid access congeners of hygromycin A. Furthermore,glycosylation with phenol derivatives provides a versatile method for establishing the unique stereogenic center of the furanoside in this class of compounds.

Asymmetric functionalization of C & horbar;C sigma bond is a straightforward way to edit molecule backbones but heavily relies on strained rings. The related process with unstrained structure is highly challenging,and only several cases are reported. However,these examples can just achieve related enantiomers through C & horbar;C sigma bond activation. The stereodivergent C & horbar;C sigma bond functionalization for precise access to all stereoisomers is unknown. Here we have established two catalytic systems to show the feasibility of unstrained C & horbar;C sigma bond functionalization as an efficient pathway in stereodivergent synthesis. Both unnatural amino acid derivatives bearing two vicinal stereocenters and carbonyl compounds containing a tertiary fluoride are constructed in good yields with high diastereo- and enantioselectivities. Stereodivergent access to all these chiral skeletons is demonstrated possible with simple dictation of ligand configurations. Mechanistic studies unveil the resolution pathway of racemic allyl substrates through diene formation instead of typical metal interconversion and C & horbar;C formation as rate-determining step.

The copper-catalysed functionalization of aryl halides is one of the most preferred methods for forming carbon-carbon and carbon-heteroatom bonds1. Yet the redox behaviour of the copper species in the catalytic cycle remains poorly understood and a subject of debate2. We report experimental and theoretical mechanistic investigations into the reaction of a well-defined Cu(I) complex with an electron-poor aryl iodide,which leads to the formation of an isolable Cu(III)-aryl complex that subsequently reductively eliminates to form a C(sp2)-CF3 bond. Our integrated experimental and theoretical findings indicate that the process proceeds through a Cu(I)/Cu(III)/Cu(II)/Cu(III)/Cu(I) redox sequence. By controlling the temperature, we managed to interrupt this sequence and capture the reactivity of the copper species through various spectroscopic methods, enabling in-depth mechanistic analysis. These findings shed light on the intricate behaviour of copper species and challenge the traditional mechanistic proposal for the reaction of Cu(I) with aryl iodide, thus providing fresh perspectives into the mechanistic aspect of the copper-catalysed coupling reactions.

Nicotinamide mononucleotide (NMN),a precursory metabolite of NAD,has been demonstrated to boost cellular NAD level that is coupled with various age-related beneficial effects in animal models. NAD-capped RNA (NAD-RNA) represents a critical but poorly studied modification at the epitranscriptomic level. Here we examine the impact of NMN supplementation on NAD-RNA in human peripheral blood mononuclear cells (PBMCs). We demonstrated that NMN supplementation increases NAD turnover coupled with a reduction in NAD-capped RNAs in both human and dog, revealing blood-derived NAD-RNAs as potential biomarkers sensitized to NMN exposure.