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We report scalable syntheses of two potent and selective kallikrein related peptidase 6 (KLK6) inhibitors, as well as X-ray crystal structures of both inhibitors as protein-ligand complexes.

We report asymmetric bioinspired total syntheses of the fungal metabolites emeriones A-C via stereoselective oxidations of two bicyclo[4.2.0]octadiene diastereomers. The central bicyclic scaffolds are prepared in an 8π/6π electrocyclization cascade of a stereodefined pentaene, which contains the fully assembled side chains of the emeriones. The anti-aldol side chain is made using a Paterson-aldol addition, and the epoxide of the dioxabicyclo[3.1.0]hexane side chain via ring-closure onto an oxidized acetal. Our work has enabled the structural revision of emerione C, and resulted in the synthesis of a "missing" family member, which we call emerione D. DFT calculations identified two methyl groups that govern torquoselectivity in the 8π/6π cascade.

The preparation and reactivity of a range of novel paramagnetic chromium(II) complexes supported by a carbazole-based PNP pincer ligand is reported. Deprotonation of the ligand precursors R(PNP)H (1R) and subsequent reaction with chromium(II) chloride led to the formation of square-planar chlorido complexes R(PNP)CrCl (2R). Further reaction with various alkylating agents resulted in the isolation of chromium alkyl complexes R(PNP)CrR' (3R-R') which were then hydrogenated to yield two rare examples of paramagnetic chromium(II) hydrides 4iPr and 4tBu. Both compounds were characterized by X-ray diffraction and paramagnetic NMR spectroscopy supported by a comprehensive DFT-supported assignment of the resonances. While the di(tert-butyl)phosphino PNP substituted complex 4tBu was found to exhibit a monomeric square-planar molecular structure, its isopropyl-substituted analog 4iPr forms a dimer, also indicated by a strong antiferromagnetic coupling of the chromium centers. The pronounced reactivity of these compounds toward C═X double bonds was demonstrated by reaction with benzophenone, N,N'-dicyclohexylcarbodiimide, and carbon dioxide, which gave the corresponding insertion products. The alkoxido complex 5iPr, the amidinato complex 6iPr, and the formato compound 7tBu were also characterized by X-ray diffraction.

Correction for ‘Scalable synthesis and structural characterization of reversible KLK6 inhibitors’ by Andreas Baumann et al., RSC Adv., 2022, 12, 26989–26993, https://doi.org/10.1039/D2RA04670A.