Enzymatic Synthesis of Noncanonical α-Amino Acids Containing γ-Tertiary Alcohols.

Noncanonical amino acids (ncAAs) containing tertiary alcohols are valuable as precursors of natural products and active pharmaceutical ingredients. However, the assembly of such ncAA scaffolds from simple material by C-C bond formation remains a challenging task due to the presence of multiple stereocenters and large steric hindrance. In this study, we present a novel solution to this problem through highly selective enzymatic decarboxylative aldol addition. This method allows for the streamlined assembly of multifunctionalized ncAAs with γ-tertiary alcohols from readily available materials, such as L -aspartatic acid and isatins, vicinal diones and keto esters. The modularity of electrophiles furnished four classes of ncAAs with decent efficiency as well as excellent site and stereocontrol. Computational modeling was employed to gain detailed insight into the catalytic mechanism and to provide a rationale for the observed selectivities. The method offers a single-step approach to producing multifunctionalized ncAAs, which can be directly utilized in peptide synthesis and bioactivity assessment.

Versatile Biocatalytic C(sp3 )-H Oxyfunctionalization for the Site- Selective and Stereodivergent Synthesis of α- and ß-Hydroxy Acids.

C(sp3 )-H oxyfunctionalization, the insertion of an O-atom into C(sp3 )-H bonds, streamlines the synthesis of complex molecules from easily accessible precursors and represents one of the most challenging tasks in organic chemistry with regard to site and stereoselectivity. Biocatalytic C(sp3 )-H oxyfunctionalization has the potential to overcome limitations inherent to small-molecule-mediated approaches by delivering catalyst-controlled selectivity. Through enzyme repurposing and activity profiling of natural variants, we have developed a subfamily of α-ketoglutarate-dependent iron dioxygenases that catalyze the site- and stereodivergent oxyfunctionalization of secondary and tertiary C(sp3 )-H bonds, providing concise synthetic routes towards four types of 92 α- and ß-hydroxy acids with high efficiency and selectivity. This method provides a biocatalytic approach for the production of valuable but synthetically challenging chiral hydroxy acid building blocks.

Size-specific particulate matter and outpatient visits for allergic conjunctivitis in children: a time-stratified case-crossover study in Guangzhou, China.

This time-stratified case-crossover study aims to quantify the risk of allergic conjunctivitis (AC) associated with short-term exposure to PMs (i.e., PM1, PM2.5, PMc, and PM10) among children in Guangzhou, China. We collected data on children's daily AC outpatient visits from the Guangzhou Women and Children Medical Center during February 20, 2016 to December 31, 2018, and also extracted air pollution and meteorological data in the same time frame. We used conditional logistic regression model to estimate the associations between PMs and AC outpatient visits, and conducted subgroup analyses stratified by sex, age, and season. During the study period, we recorded 39,330 children's outpatient visits for AC, including 27,638 boys and 11,692 girls. The associations between PMs and AC were general linear with no clear threshold, which were largest at the current days but remained positive for lag 1 to 3 days. For every 10 µg/m3 increase in daily PM1, PM2.5, PMc, and PM10 concentrations, the estimated risks of AC outpatient visits at the current days increased by 2.5% (OR = 1.025, 95% CI: 1.011-1.039), 1.8% (OR = 1.018, 95% CI: 1.009-1.027), 2.1% (OR = 1.021, 95% CI: 1.004-1.039), and 1.3% (OR = 1.013, 95% CI: 1.007-1.020), respectively. In addition, our stratified analyses revealed that girls and children aged 1 to 6 years were more sensitive to PM exposure, and the PM-associated risks for AC were more apparent in autumn and winter. Our study suggests that short-term exposure to PMs may induce AC in children.