Development of a potent and selective cell penetrant Legumain inhibitor.

This Letter describes the continued SAR exploration of small molecule Legumain inhibitors with the aim of developing a potent and selective in vitro tool compound. Work continued in this Letter explores the use of alternative P2-P3 linker units and the P3 group SAR which led to the identification of 10t, a potent, selective and cellularly active Legumain inhibitor. We also demonstrate that 10t has activity in both cancer cell viability and colony formation assays.

Total synthesis of chivosazole F.

The first synthesis of the highly biologically active chivosazole F is described. It features an intramolecular Stille coupling for the macrolactone formation and thereby circumvents the problem of isomerization associated with the tetraene segment. Additionally, the synthesis confirms the structure which has been proposed based solely on a combination of NMR/computational methods and genetic analysis.

Gold-catalyzed reactions of 1,5- and 1,6-enynes with carbonyl compounds: cycloaddition vs. metathesis.

Gold and rings: The gold(I)-catalyzed addition of aldehydes to 1,6-enynes gives 1,3-dienes, by a cycloaddition/fragmentation process. 1,5-Enynes react with aldehydes and ketones by the 5-endo-dig pathway to give the corresponding cycloadducts.