C1 Nitrogen iminocyclitols are potent inhibitors of N-acetyl-beta-hexosaminidases. Given hexosaminidases' important roles in osteoarthritis, we developed two straightforward and efficient syntheses of C1 nitrogen iminocyclitols from two readily available starting materials, D-mannosamine hydrochloride and the microbial oxidation product of fructose. A diversity-oriented synthetic strategy was then performed by coupling these core structures with various aldehydes, carboxylic acids, and alkynes to generate three separate libraries. High-throughput screening of the generated libraries with human N-acetyl-beta-hexosaminidases produced only moderate inhibitory activities. However, the synthetic approach and screening strategy for these compounds will be applied to develop new potent inhibitors of human N-acetyl-beta-hexosaminidases, particularly when combined with the structural information of these enzymes.

Potent library. Anthrax lethal factor (LF) is a zinc‐dependent metalloprotease involved in the rapid development of the deadly infection caused by Bacillus anthracis. Blocking its action is a plausible method to mitigate the deleterious effects of late stage infection. We report the inhibition of LF by tetrahydro‐isoquinoline polyphenolic compounds, such as 5 a, which were identified by screening a combinatorial library that was generated by Pictet–Spengler reaction. We also report the identification of commercially available polyphenolic inhibitors against LF.

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An efficient method for the synthesis of enantiopure carbasugars with a C 6 -or symmetrical C 7 -ring has been developed from C 2 -symmetric bis-epoxides issued from D-mannitol. The methodology involves a tandem alkylation-cyclization with 2lithio-1,3-dithiane derivatives.