Synthesis and Biological Activity of Kalkitoxin and its Analogues

Total syntheses of kalkitoxin, isolated from the Caribbean <i>Lyngbya majuscula</i>, and its analogues, 3-<i>epi</i>-, 7-<i>epi</i>-, 8-<i>epi</i>-, 10-<i>epi</i>-, 10-<i>nor</i>-, and 16-<i>nor</i>-kalkitoxin, were achieved via oxazolidinone-based diastereoselective 1,4-addition reaction of a methyl group and efficient TiCl₄-mediated thiazoline ring formation as the key steps. The biological activities of synthetic kalkitoxin and its analogues were evaluated with brine shrimp

Foxo3a Inhibitors of Microbial Origin, JBIR-141 and JBIR-142

JBIR-141 (<b>1</b>) and JBIR-142 (<b>2</b>) were discovered as potent Foxo3a inhibitors that consist of three quite unique substructures, a 1-((dimethylamino)­ethyl)-5-methyl-4,5-dihydrooxazole-4-carboxylic acid that is originated from Ala-Thr amino acid residues, a 3-acetoxy-4-amino-7-(hydroxy­(nitroso)­amino)-2,2-dimethylheptanoic acid, and an α-acyl tetramic acid fused with a 2-methylpropan-1-ol moiety. Their structures involving absolute configurations were determined by spectroscopic data, chemical degradation, anisotropy methods, and LC–MS analyses of diastereomeric derivatives. Compounds <b>1</b> and <b>2</b> exhibited specific inhibition against Foxo3a transcriptional activity with IC₅₀ values of 23.1 and 166.2 nM, respectively