Teixobactin represents a new class of antibiotics with novel structure and excellent activity against Gram-positive pathogens and Mycobacterium tuberculosis . Herein, we report a one-pot reaction to conveniently construct the key building block l -allo-Enduracidine in 30-gram scale in just one hour  and a convergent strategy (3 + 2 + 6) to accomplish a gram-scale total synthesis of teixobactin. Several analogs are described, with 20 and 26 identified as the most efficacious analogs with 3~8-fold and 2~4-fold greater potency against vancomycin resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus respectively in comparison with teixobactin. In addition, they show high efficiency in Streptococcus pneumoniae septicemia mouse model and neutropenic mouse thigh infection model using methicillin-resistant Staphylococcus aureus . We also propose that the antiparallel β-sheet of teixobactin is important for its bioactivity and an antiparallel dimer of teixobactin is the minimal binding unit for lipid II via key amino acids variations and molecular docking.

Teixobactin, targeting lipid II, represents a new class of antibiotics with novel structures and has excellent activity against Gram-positive pathogens. We developed a new convergent method to synthesize a series of teixobactin analogues and explored structure-activity relationships. We obtained equipotent and simplified teixobactin analogues, replacing the l- allo-enduracididine with lysine, substituting oxygen to nitrogen on threonine, and adding a phenyl group on the d-phenylalanine. On the basis of the antibacterial activities that resulted from corresponding modifications of the d-phenylalanine, we propose a hydrophobic interaction between lipid II and the N-terminal of teixobactin analogues, which we map out with our analogue 35. Finally, a representative analogue from our series showed high efficiency in a mouse model of Streptococcus pneumoniae septicemia.

Background and Aims Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a pivotal role in the establishment and persistence of HBV infection. Understanding the turnover time of preexisting cccDNA pools would be helpful in designing strategies to clear HBV by fully blocking the de novo generation of cccDNA. Approach and Results In this study, we retrospectively monitored the emergence and reversion of the rtM204I/V mutant, a signature lamivudine resistance (LAMR) mutation serving as a biomarker of cccDNA turnover in liver biopsies and longitudinal serum samples from two clinical trials. Methodologies were optimized to differentially isolate and sequence HBV virion DNA, cccDNA, and HBV RNA from clinical samples. A strong correlation was observed between LAMR composition of cccDNA with that of serum and intrahepatic HBV RNA in paired liver and serum samples (r = 0.96 and 0.90, respectively), suggesting that serum HBV RNA can serve as a surrogate marker of cccDNA genetic composition when liver biopsies are unavailable. LAMR mutations emerged and increased from undetectable to 40%‐90% within 16‐28 weeks in serum HBV RNA from telbivudine‐treated patients experiencing virological breakthrough. Similarly, in lamivudine‐resistant patients who switched to interferon therapy, serum HBV‐RNA population bearing 100% LAMR mutations fully reversed back to wild type within 24‐48 weeks. Conclusions The genetic composition dynamics of serum HBV RNA and biopsy cccDNA in treated HBV patients indicates that cccDNA turnover occurs relatively rapidly (several months), offering a possibility of HBV cure with finite therapy through completely blocking cccDNA replenishment.

All the hype: The title reaction has been developed for the facile synthesis of a variety of complex alkyl ethers. Cyclic hypervalent iodine (I(3+) ) reagents serve as oxidants for this unique CH alkoxylation reaction. The reaction demonstrates excellent reactivity, good functional-group tolerance, and high yields. Q=8-aminoquinoline-derived auxiliary.

We fabricated depth-type hierarchical CNT/quartz fiber (QF) filters through in situ growth of CNTs upon quartz fiber (QF) filters using a floating catalyst chemical vapor deposition (CVD) method. The filter specific area of the CNT/QF filters is more than 12 times higher than that of the pristine QF filters. As a result, the penetration of sub-micron aerosols for CNT/QF filters is reduced by two orders of magnitude, which reaches the standard of high-efficiency particulate air (HEPA) filters. Simultaneously, due to the fluffy brush-like hierarchical structure of CNTs on QFs, the pore size of the hybrid filters only has a small increment. The pressure drop across the CNT/QF filters only increases about 50% with respect to that of the pristine QF filters, leading to an obvious increased quality factor of the CNT/QF filters. Scanning electron microscope images reveal that CNTs are very efficient in capturing sub-micron aerosols. Moreover, the CNT/QF filters show high water repellency, implying their superiority for applications in humid conditions.