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Relevant academic research and scientific papers

Divergent synthesis of α-functionalized amides through selective N-O/C-C or N-O/C-C/C-N cleavage of aza-cyclobutanone oxime esters

Herein, a novel sequential ring opening reaction of aza-cyclobutanone oxime esters with isocyanides is described. The reaction proceeded smoothly under redox-neutral and mild conditions, leading to a divergent synthesis of α-cyanomethylaminoamides, α-acyloxyamides and α-acylaminoamides. In these transformations, a selective N-O/C-C or N-O/C-C/C-N cleavage was achieved only by changing the iron-catalyst system. Among them, a rare sequential N-O/C-C/C-N cleavage process with a classical Passerini or Ugi multicomponent reaction can be executed in a single step. To the best of our knowledge, this work creates a novel reaction mode of cycloketone oximes and provides new opportunities for reaction design.

Structural and biochemical study on the inhibitory activity of derivatives of 5-nitro-furan-2-carboxylic acid for RNase H function of HIV-1 reverse transcriptase

Rapid emergence of drug-resistant variants is one of the most serious problems in chemotherapy for HIV-1 infectious diseases. Inhibitors acting on a target not addressed by approved drugs are of great importance to suppress drug-resistant viruses. HIV-1 reverse transcriptase has two enzymatic functions, DNA polymerase and RNase H activities. The RNase H activity is an attractive target for a new class of antiviral drugs. On the basis of the hit chemicals found in our previous screening with 20,000 small molecular-weight compounds, we synthesized derivatives of 5-nitro-furan-2-carboxylic acid. Inhibition of RNase H enzymatic activity was measured in a biochemical assay with real-time monitoring of florescence emission from the digested RNA substrate. Several derivatives showed higher inhibitory activities that those of the hit chemicals. Modulation of the 5-nitro-furan-2-carboxylic moiety resulted in a drastic decrease in inhibitory potency. In contrast, many derivatives with modulation of other parts retained inhibitory activities to varying degrees. These findings suggest the binding mode of active derivatives, in which three oxygen atoms aligned in a straight form at the nitro-furan moiety are coordinated to two divalent metal ions located at RNase H reaction site. Hence, the nitro-furan-carboxylic moiety is one of the critical scaffolds for RNase H inhibition. Of note, the RNase H inhibitory potency of a derivative was improved by 18-fold compared with that of the original hit compound, and no significant cytotoxicity was observed for most of the derivatives showing inhibitory activity. Since there is still much room for modification of the compounds at the part opposite the nitro-furan moiety, further chemical conversion will lead to improvement of compound potency and specificity.