A Radical Approach for Asymmetric α-C-H Addition of N-Sulfonyl Benzylamines to Aldehydes.

Efficient synthesis of enantioenriched amines is of great importance due to their significant synthetic and biological applications. Photoredox-mediated asymmetric α-amino C(sp3)-H functionalization offers an atom-economical and sustainable approach to access chiral amines. However, the development of analogous reactions is in its early stages, generally affording chiral amines with a single stereocenter. Herein, we present a novel synergistic triple-catalysis approach for the asymmetric α-C-H addition of readily available N-sulfonyl amines to aldehydes under mild conditions. This method allows for the efficient synthesis of a diverse array of valuable ß-amino alcohols bearing vicinal stereocenters. Unlike previous reports, our protocol employs a radical approach using earth-abundant Cr catalysis. Quinuclidine plays a dual role by facilitating highly selective hydrogen-atom transfer to generate α-amino radicals and promoting the dissociation of the Cr-O bond, which is crucial for the overall catalytic cycle as evidenced by control, NMR, and DFT experiments. Preliminary mechanistic studies, including radical trapping, nonlinear effect, Stern-Volmer plot, kinetic isotope effect, and Hammett plot, offer valuable insights into the reaction pathway.

Chromium Catalyzed Asymmetric Reformatsky Reaction.

This study describes an unprecedented chromium-catalyzed asymmetric Reformatsky reaction, enabling the synthesis of chiral ß-hydroxy carbonyl compounds from α-chlorinated or α-brominated esters and amides. By employing a chiral chromium/diarylamine bis(oxazoline) catalyst, we achieved relatively broad functional group tolerance. Distinct from known reports, the protocol operates under both classical and photoredox conditions, facilitated by the in situ formation of a nucleophilic chiral chromium intermediate through a radical-polar crossover mechanism. Preliminary mechanistic insights, supported by DFT calculations, identify the nucleophilic aldehyde addition as the key stereo-determining step. This approach not only overcomes the limitations of existing Reformatsky reactions but also provides a versatile strategy for accessing complex chiral molecules.

Radical-Based Enantioconvergent Reductive Couplings of Racemic Allenes and Aldehydes.

Transition metal-catalyzed radical-based enantioconvergent reactions have become a powerful strategy to synthesize enantiopure compounds from racemic starting materials. However, existing methods primarily address precursors with central chirality, neglecting those with axial chirality. Herein, we describe the enantioconvergent reductive coupling of racemic allenes with aldehydes, facilitated by a photoredox, chromium, and cobalt triple catalysis system. This method selectively affords one product from sixteen possible regio- and stereoisomers. The protocol leverages CoIII-H mediated hydrogen atom transfer (MHAT) and Cr-catalyzed radical-polar crossover for efficient stereoablation of axial chirality and asymmetric addition, respectively. Supported by mechanistic insights from control experiments, deuterium labeling, and DFT calculations, our approach offers synthetic chemists a valuable tool for creating enantioenriched chiral homoallylic alcohols, promising to advance radical-based strategies for synthesizing complex chiral molecules.

A novel lysin Ply1228 provides efficient protection against Streptococcus suis type 2 infection in a murine bacteremia model.

Streptococcus suis is an important zoonotic pathogen that is difficult to control with antibiotics due to the widespread development of multidrug-resistant strains. Phage lysin is considered a potential therapeutic agent to combat S. suis. In this study, the novel lysin Ply1228 derived from the prophage of S. suis type 12 was identified. Bioinformatics analysis showed that Ply1228 contains a CHAP catalytic domain, which is a binding domain composed of a CW-7 binding motif and an amidase-2 catalytic domain. The CHAP catalytic domain is essential for the bactericidal function of lysin Ply1228 and does not depend on the presence of Ca2+. C34 and H99 of the CHAP domain were identified as the key active sites. The CW-7 binding motif plays a key binding role in Ply1228. Ply1228 can specifically lyse S. suis, including types 2, 3, 7, 9, 10, 12, 14, and 27. Within 10 min, Ply1228 killed 4 log of the S. suis population, which had a starting concentration of approximately 107 CFU/mL. In addition, Ply1228 showed favourable thermal and pH stability. The therapeutic effect of Ply1228 was further investigated in a mouse model of S. suis bacteremia. The administration of the lysin Ply1228 (200 µg/mouse) 1 h after the intraperitoneal injection of 2 × MLD of SS2 strain SC225 was sufficient to protect the mice (P < 0.0001) and significantly reduced the bacterial loads in the blood and organs (livers, spleens, lungs and kidneys). The levels of inflammation and histopathological damage in infected mice were effectively relieved after the Ply1228 treatment. These results indicate that Ply1228 might represent a new enzybiotic candidate for S. suis infection.