Axially chiral biaryl dimethanols are ubiquitous and multifunctional intermediates for the synthesis of valuable atropisomeric molecules in advanced materials, drugs, natural products, and organocatalysts. Despite their broad synthetic utility, direct enantiodivergent catalytic access to this specific class of compounds remains largely unexplored, particularly in biocatalysis. Herein, we report a biocatalytic platform for enantiodivergent and atroposelective dynamic kinetic carbonyl reduction via transient seven-membered cyclic lactol intermediates. These engineered alcohol dehydrogenase (ADH)-driven transformations deliver up to 99% yield and enantioselectivity (>99:1 e.r. and < 1:99 e.r). This strategy demonstrates broad substrate compatibility, extending even to complementary “flipped” substrate series. Furthermore, the protocol is readily scalable to gram quantities and accommodates diverse downstream derivatizations. Mechanistic experiments and theoretical calculations delineate the pathway and illuminate the origin of enzymatic stereocontrol.
Jie Chen, Zhuoting Peng, Xiaolong Gao et al.· ACS Catalysis· 0 citations
T-2 toxin is a prevalent mycotoxin that poses a substantial threat to male reproductive health, while effective protective strategies remain limited. This study evaluated the protective effects of quercetin (Qu), a natural flavonoid, against T-2 toxin-induced testicular injury and investigated the underlying mechanisms, focusing on NLRP3 inflammasome-associated inflammation and fibrotic remodeling. Male ICR mice were exposed to T-2 toxin (1 mg/kg) for 28 days, with or without Qu (50 mg/kg) or the NLRP3 inhibitor MCC950 (20 mg/kg). Testicular morphology, TLR4/MyD88/NLRP3 pathway activation, pyroptosis-associated molecular changes, fibrotic remodeling, and blood-testis barrier (BTB)-associated proteins were assessed using histological staining, immunofluorescence, immunohistochemistry, and Western blotting. T-2 toxin exposure caused marked testicular histopathological alterations and activated the TLR4/MyD88/NLRP3 pathway, accompanied by increased IL-1β and IL-18 levels and alterations in pyroptosis-associated molecular markers in Leydig and Sertoli cells (P < 0.05). These changes were associated with increased TGF-β1 expression and peritubular collagen deposition, suggesting early fibrotic remodeling (P < 0.05). T-2 toxin also reduced the expression of the BTB-associated proteins ZO-1, occludin, CX43, claudin-1, and β-catenin (P < 0.05). Qu treatment attenuated testicular pathological changes and inflammasome-associated inflammatory responses, reduced early fibrotic remodeling, and restored BTB-associated protein expression. MCC950 intervention further supported the involvement of NLRP3 inflammasome-associated signaling in T-2 toxin-induced testicular injury. Collectively, these findings suggest that Qu alleviates T-2 toxin-induced testicular injury, at least in part, by modulating NLRP3 inflammasome-associated inflammation and fibrotic remodeling, thereby maintaining testicular homeostasis. Qu may therefore have potential for mitigating mycotoxin-induced reproductive toxicity. Nevertheless, because the conclusions regarding pyroptosis are based primarily on pathway-associated molecular markers in a murine model, further studies incorporating direct assessments of pyroptotic cell death and validation in higher-order animal models and clinical settings are warranted.
Xinzi Guo, Mingfa Yang, Yisheng Wang et al.· Toxicon· 0 citations
