Metalloids bridge the properties of metals and nonmetals, creating unique opportunities in drug discovery. However, the potential of silicon- and germanium-containing scaffolds in organic synthesis and medicinal chemistry remain underexplored, largely owing to the lack of general stereocontrolled synthetic methods, particularly for value-added chiral α-silylamines and α-germylamines. Here, we report a robust nickel-catalyzed enantioselective decarboxylative cross-coupling of amino acid or peptide-derived redox-active esters with silylzinc and germylzinc reagents. The method exhibits a broad substrate scope and delivers excellent performance under mild conditions. Its efficacy is further demonstrated through the late-stage diversification of complex bioactive peptides, and both enantiomers can be accessed with high stereochemical fidelity. Mechanistic investigations delineate the origin of stereocontrol, while preliminary biological evaluations show promising activities, with Ge substitution in several cases surpassing Si and certain clinically marketed boron-containing drugs. Collectively, this work establishes an efficient and enantioselective route to chiral α-silylamines and α-germylamines, underscoring their potential to expand peptide chemical space and to enable the development of peptide-based therapeutics and diagnostics.
Qiang Tao, Yu-Juan Wang, Kai-Ge Lu et al.· Journal of the American Chem...· 0 citations
28-epi-homobrassinolide (28-epi-HBL), a bioactive analog of the steroidal phytohormone brassinolide, exhibits broad biological activities and considerable application potential. However, conventional chemical routes remain limited by tetrahydroxylation step that relies on highly toxic osmium tetroxide in combination with costly chiral ligands, whereas the Baeyer-Villiger oxidation step requires strong oxidants and often exhibits limited regioselective control. In this work, optimization of tetrahydroxylation was achieved using the Shing-Plietker reaction, thereby avoiding the use of osmium tetroxide. Moreover, an engineered Baeyer-Villiger monooxygenase (CpnB_BL) was heterologously expressed and used for regioselective B-ring lactonization under mild conditions. A ZIF-8-based immobilization strategy was established for this engineered enzyme, further improving its stability and solvent tolerance, and increasing the isolated yield of the Baeyer-Villiger step to 83%. These optimized strategies were subsequently applied to the total synthesis of 28-epi-HBL, achieving an overall yield of 44.9%. This represents a marked improvement over the highest previously reported yield in the literature, which stands at approximately 20%. Collectively, this study lays the groundwork for the development of more precise and sustainable synthetic routes to 28-epi-HBL.
Chuan-Yu Fu, Ruoyu Jiao, Yunyijie Zhou et al.· Biotechnology and Bioenginee...· 0 citations
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