Controllable fluorocarbon chain elongation (CFCE) is a promising yet underdeveloped strategy for the well-defined synthesis of structurally novel polyfluorinated compounds. Herein, the direct and efficient trifluorovinylation and pentafluorocyclopropylation of aldehydes are described by using TMSCF2Br (TMS = trimethylsilyl) as the sole fluorocarbon source, accomplishing the goals of CFCE from C-1 to C-2 and from C-1 to C-3, respectively. The key to the success of these CFCE processes lies in the unique and diversified chemical reactivity of TMSCF2Br, which can serve as two different precursors, namely, a TMSCF2 radical precursor and a difluorocarbene precursor. Various functional groups are amenable to this new synthetic protocol, providing streamlined access to a broad range of alcohols containing trifluorovinyl or pentafluorocyclopropyl moieties from abundantly available aldehydes. The potential utility of these methods is further demonstrated by the gram-scale synthesis, derivatization, and measurement of log P values of the products.

HER3 (Human Epidermal Growth Factor Receptor 3) is frequently overexpressed in various cancers, including non-small cell lung cancer (NSCLC), with a prevalence of 83% in primary tumors. Its involvement in tumorigenesis and resistance to targeted therapies makes HER3 a promising target for cancer treatment. Despite being initially considered undruggable due to its lack of catalytic activity, significant progress has been made in the development of anti-HER3 therapeutics. Monoclonal antibodies such as lumretuzumab, seribantumab, and patritumab have shown potential in targeting HER3 to overcome resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Additionally, antibody-drug conjugates (ADCs) like HER3-DXd (patritumab deruxtecan) are new drug candidates that have demonstrated selective delivery of cytotoxic chemicals to NSCLC cells by exploiting HER3's widespread expression, minimizing cytotoxicity. This review aims to evaluate the efficacy of current HER3 therapeutics in development and their therapeutic potential in NSCLC, incorporating evidence from clinical trials.

The role of gut microbiota in insulin resistance (IR), Metabolic Syndrome (MetS), and Type 2 Diabetes Mellitus (T2DM) is rapidly gaining recognition. However, the mechanisms and implications of gut bacteria in these conditions remain enigmatic. This commentary not only highlights the findings of a recent multi-omics study by Takeuchi et al. but also offers a unique perspective by integrating personal opinions and insights. The discussion revolves around the intricate connection between gut microbes and IR, suggesting novel therapeutic potential in targeting gut microbial carbohydrate metabolism for improved IR management and metabolic health.

Chemical synthesis of an orthogonally protected hexasaccharide relevant to the reducing-end half of axinelloside A, a highly sulfated marine lipopolysaccharide, is disclosed. The synthesis features preparation of the scyllo-inositol unit via a Ferrier-type-II rearrangement, construction of the 1,2-cis-glycosidic bonds via remote participation, and concise [2+2+2] assembly via Au(I)-catalyzed glycosylation. A properly protected hexasaccharide relevant to the reducing-end half of telomerase inhibitor axinelloside A was synthesized. Features of the synthetic approach include (1) preparation of the scyllo-inositol unit via Ferrier-type-II rearrangement, (2) formation of the 1,2-cis-glycosidic linkages via remote acyl group participation, and (3) concise [2+2+2] assembly by virtue of Au(I)-catalyzed glycosylation.+ image

Studies toward transition metals in negative oxidation states are much less explored compared to those in zero or positive oxidation states. In this study, we present the synthesis and reactivity studies of an Fe(-II) carbonyl dianion (3) featuring an appended Lewis base, [(L)Fe(CO)3]2- (L=Ph2PCH2CH2NMe2). Unlike the well-known reactivity of [Fe(CO)4]2- with common electrophiles (E+) which typically forms [(E)2Fe(CO)4], 3 reacted with 2 equiv. of Ph3SnCl to afford a mixture of two products: one being an Fe(II) bis(triphenylstannyl) product (4), and the other an Fe stannylene product (5). Further insights into the reactivity of 3 was elucidated through its reactions with 2 equiv. of Cy3SnCl or Me3SiCl, producing an Fe(II) bis(tricyclohexylstannyl) product (8) and a zwitterionic complex (11), respectively, the latter emerging via THF ring-opening. Intermediates generated from reactions of 3 with 1 equiv. of each electrophile were isolated to shed light on the reaction mechanisms, highlighting the influence of appended Lewis base on the reactivity of metal carbonyl dianions, especially the generation of the novel stannylene complex 5. The electronic structure of this paramagnetic stannylene complex was also investigated by computational studies. Reactions of an Fe(-II) carbonyl dianion bearing an amino appendant with diverse electrophiles generated a range of unprecedented products, most notably a diphenylstannylene complex formed via chelate-assisted oxidative addition of Sn-Ph bond. The amino appendant is proposed to play a pivotal role in differentiating the reactivity of this dianion to the basic [Fe(CO)4]2- species.image

An efficient method for the late-stage selective O-fluoroalkylation of tyrosine residues with a stable yet highly reactive fluoroalkylating reagent, 3,3-difluoroallyl sulfonium salts (DFASs), has been developed. The reaction proceeds in a mild basic aqueous buffer (pH = 11.6) with high efficiency, high biocompatibility, and excellent regio- and chemoselectivity. Various oligopeptides and phenol-containing bioactive molecules, including carbohydrates and nucleosides, could be selectively O-fluoroalkylated. The added vinyl and other functional groups from DFASs can be valuable linkers for successive modification, significantly expanding the chemical space for further bioconjugation. The synthetic utility of this protocol has been demonstrated by the fluorescently labeled anti-cancer drug and the synthesis of O-link type 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid-tyrosine(3)-octreotate (DOTA-TATE), showing the prospect of the method in medicinal chemistry and chemical biology.

The limited surface coverage and activity of active hydrides on oxide surfaces pose challenges for efficient hydrogenation reactions. Herein, we quantitatively distinguish the long-puzzling homolytic dissociation of hydrogen from the heterolytic pathway on Ga2O3, that is useful for enhancing hydrogenation ability of oxides. By combining transient kinetic analysis with infrared and mass spectroscopies, we identify the catalytic role of coordinatively unsaturated Ga3+ in homolytic H-2 dissociation, which is formed in-situ during the initial heterolytic dissociation. This site facilitates easy hydrogen dissociation at low temperatures, resulting in a high hydride coverage on Ga2O3 (H/surface Ga3+ ratio of 1.6 and H/OH ratio of 5.6). The effectiveness of homolytic dissociation is governed by the Ga-Ga distance, which is strongly influenced by the initial coordination of Ga3+. Consequently, by tuning the coordination of active Ga3+ species as well as the coverage and activity of hydrides, we achieve enhanced hydrogenation of CO2 to CO, methanol or light olefins by 4-6 times.

Sortase-mediated ligation (SML) is widely used for protein bioconjugation. However, the sortase used in this strategy typically recognizes only the N-terminal oligoglycine, which is absent in most natural proteins. To broaden the spectrum of substrates compatible with SML, we focus on a novel sortase, sortase A from Streptococcus pneumoniae (SpSrtA), known for its expanded substrate specificity (N-terminal glycine, alanine, and serine). We present the first evidence showing that the reported SpSrtA mutant (SpSrtA*) can modify lysine residues in itself and other proteins. The modification sites of SpSrtA* were identified through LC-MS/MS analysis. Moreover, we discovered an optimal lysine-containing peptide tag by fusing it onto sfGFP, resulting in a labeling efficiency of 57%. Inspired by this, we applied the method to modify proteins on microorganism surfaces up to 13.5-fold. To enhance labeling efficiency, we fused the SpSrtA* onto a surface protein and achieved a 2.64-fold improvement. We further developed a high-throughput yeast display screening method for the directed evolution of SpSrtA*, achieving a 10-fold improvement in the labeling efficiency of this surface protein. Our study provides a novel strategy for modifying the lysine residues that will be a powerful addition to the protein bioconjugation toolbox.