Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents.

7-Ethyl-10-hydroxycamptothecin (SN38), a highly potent metabolite of irinotecan, has an anticancer efficacy 100-1000 folds more than irinotecan . However, the clinical application of SN38 has been limited due to the very narrow therapeutic window and poor water solubility. Herein, we report the SN38-glucose conjugates (Glu-SN38) that can target cancer cells due to their selective uptake glucose transporters, which are overexpressed in most cancers.

An orally available M inhibitor is effective against wild-type SARS-CoV-2 and variants including Omicron.

Emerging SARS-CoV-2 variants continue to cause waves of new infections globally. Developing effective antivirals against SARS-CoV-2 and its variants is an urgent task. The main protease (M) of SARS-CoV-2 is an attractive drug target because of its central role in viral replication and its conservation among variants.

A base-promoted cascade reaction of α,β-unsaturated N-tosylhydrazones with o-hydroxybenzyl alcohols: highly regioselective synthesis of N-sec-alkylpyrazoles.

An efficient method for the synthesis of N-sec-alkylpyrazoles through a base-promoted cascade cyclization/Michael addition reaction of α,β-unsaturated N-tosylhydrazones with ortho-hydroxybenzyl alcohols has been developed. The desired products containing di- or triaryl groups at the same carbon atom were afforded in good to excellent yields with excellent regioselectivities (>20 : 1). Moreover, a three-component reaction of ortho-hydroxybenzyl alcohols, α,β-unsaturated N-tosylhydrazones and saturated N-tosylhydrazones also took place to afford pyrazoles in good yields.

Metal-Free Ring-Expansion Reaction of Six-membered Sulfonylimines with Diazomethanes: An Approach toward Seven-Membered Enesulfonamides.

A new metal-free, ring-expansion reaction of six-membered N-sulfonylimines with unstable diazomethanes, generated in situ from the N-tosylhydrazones, has been developed. This reaction delivers valuable seven-membered enesulfonamides by a Tiffeneau-Demjanov rearrangement and intramolecular proton transfer tautomerization process. Moreover, this ring-expansion reaction can be carried out in a one-pot fashion and scaled up to the gram scale by using aryl aldehydes, without the need to isolate the N-tosylhydrazone.