Inhibition of CFTR-mediated intestinal chloride secretion by nornidulin: Cellular mechanisms and anti-secretory efficacy in human intestinal epithelial cells and human colonoids.

Secretory diarrhea, a major global health concern, particularly among young children, is often characterized by excessive chloride secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) channel. Nornidulin, a fungus-derived natural product from Aspergillus unguis, has previously been shown to inhibit cAMP-induced Cl- secretion in T84 cells (human intestinal cell lines). However, the cellular mechanism of nornidulin in inhibiting cAMP-induced Cl- secretion and its anti-secretory efficacy is still unknown especially in a human colonoid model, a preclinical model recapitulating intestinal physiology in humans.

Total Synthesis and Biological Evaluation of Mutolide and Analogues.

The convergent total syntheses of three 14-membered macrolide natural products, mutolide, nigrosporolide and (4S,7S,13S)-4,7-dihydroxy-13-tetradeca-2,5,8-trienolide have been achieved. The key synthetic features include Shiina macrolactonization to assemble the 14-membered macrocyclic core, Wittig or Still-Gennari olefination and selective reduction of propargylic alcohol to construct the E- or Z-olefins. Cross metathesis was also highlighted as an efficient tool to forge the formation of E-olefin.