ABSTRACT
Aftobetin is a non-invasive diagnosis probe of Alzheimer's disease, that can bind with aggregated ß-amyloid peptide in eye's lenses, used for early diagnosis of Alzheimer's disease in a rapid and painless mode. The reported synthesis of this probe fell short in the aspects of greenness and economy due to the involvement of toxic Chromium(IV) oxidant, noble palladium catalyst, elevated reaction temperature, the long reaction time as well as the cumbersome workup. Herein, a holistic optimization of the synthetic process was achieved via the employment of flow technology and heterogenous photocatalysis. Firstly, the integration of heterogenous carbon nitrides photocatalysis and circulation flow technology furnished the air oxidation of alcohol and nickel catalyzed C-N coupling at 20-g scale, thus avoiding the use of toxic Chromium and precious palladium species respectively. Flow-intensified esterification between acyl chloride and alcohol, just taking 30 seconds replaced the Steglich esterification of 6 hours, also avoiding the generation of difficult-to-remove dicyclohexylurea. Finally, C-N coupling, esterification and Knoevenagel condensation were telescoped together, thus simplifying the reaction workup. This fully-flow protocol led to the on-demand synthesis of eight probes.
ABSTRACT
Objective: Wild animal pathogen surveillance will help to understand the next possible pandemic in advance. Rodents, which have close contact with humans, are generally regarded as a key factor for zoonotic disease control. Given the variation in rodent virus composition in diverse ecologies, we conducted a study on the viral infection of rodents of diverse species in different typical environments of Heilongjiang and Yunnan Provinces, located in northeastern and southwestern China, respectively. Methods: Viral metagenomics sequencing and bioinformatic analysis were performed to determine the different distributions of rodent-borne viruses in typical environments of Heilongjiang and Yunnan Provinces, China. After viral culture and PCR confirmation, genomic and phylogenetic quantitative analysis was performed on the detected hantaviruses (HVs) and Beilong viruses (BeiVs). Results: Nineteen rodents from three species and 35 rodents from five species of rodents were collected from Heilongjiang and Yunnan Provinces, respectively. Although the number and number of species of rodents trapped in the northeast were fewer than those in the southwest, viruses annotated from rodents in Heilongjiang were more diverse than those in Yunnan. Rodents carried 22 virus families in Heilongjiang and 13 families in Yunnan. Sequences assembled from Rattus norvegicus were annotated to the M, L, and S segments of HV, and all were clustered within the Seoul-type hantavirus (SEOV). There were 2 (R81Q, S698T) and 4 (K153R, M168I, I279S, and R1790K) amino acid site substitutions in M and L compared with the versions in the most homologous strains. Two BeiV isolates from Rattus norvegicus were closely related to BeiV from brown rats in Hong Kong, with high bootstrap values of >90% in the N segment and > 95% in the L segment. They were further clustered with Tailam virus, forming a distinct group in Paramyxoviridae. Conclusion: The rodents from Heilongjiang and Yunnan located in northeast and southwest China, respectively, had different viral spectra, and only one-third (10/32) of virus families were detected in both areas. The predominant viruses were HV and BeiV in the Hantaviridae and Paramyxoviridae families, respectively. Rodent-borne viruses in the same species were similar in different geographic disparate areas owing to their similar close contact with human habitats and human activities. Additional attention should be given to the monitoring of neglected rodent-borne viruses, especially opportunistic viruses with currently low loads.