The 1 H and 13 C NMR chemical shifts of 48 industrially preferred solvents in six commonly used deuterated NMR solvents (CDCl 3 , acetone-d 6 , DMSO-d 6 , acetonitrile-d 3 , methanol-d 4 , and D 2 O) are reported. This work supplements the compilation of NMR data published by Gottlieb, Kotlyar, and Nudelman (J. Org. Chem. 1997, 62, 7512) by providing spectral parameters for solvents that were not commonly utilized at the time of their original report. Data are specifically included for solvents, such as 2-Me-THF, n-heptane, and iso-propyl acetate, which are being used more frequently as the chemical industry aims to adopt greener, safer, and more sustainable solvents. These spectral tables simplify the identification of these solvents as impurities in NMR spectra following their use in synthesis and workup protocols.

We report herein that the oroidin-derived alkaloids, palau’amine (1), dibromophakellin (2) and dibromophakellstatin (3) inhibit the proteolytic activity of the human 20S proteasome as well as the i20S immunoproteasome catalytic core. Palau’amine is found to prevent the degradation of ubiquitinylated proteins, including IκBα, in cell culture, which may be indicative of the potential mechanism by which these agents exhibit their exciting cytotoxic and immunosuppressive properties.

The proteasome represents an invaluable target for the treatment of cancer and autoimmune disorders. The application of proteasome inhibitors, however, remains limited to blood cancers because their reactive headgroups and peptidic scaffolds convey unfavorable pharmacodynamic properties. Thus, the discovery of more drug-like lead structures is indispensable. In this study, we present the first structure of the proteasome in complex with an indolo-phakellin that exhibits a unique noncovalent binding mode unparalleled by all hitherto reported inhibitors. The natural product inspired pentacyclic alkaloid binds solely and specificially into the spacious S3 subpocket of the proteasomal β5 substrate binding channel, gaining major stabilization through halogen bonding with the protein backbone. The presented compound provides an ideal scaffold for the structure-based design of subunit-specific nonpeptidic proteasome-blockers.

(±)-Dibromophakellin has been synthesized in two steps from a known alkene intermediate. The key step in the synthesis is the NBS olefin activation to facilitate the addtion of a guanidine molecule across the double bond.

This work reviews the reactivity of oxazolones and their application in the synthesis of natural products. In particular, the focus is on the development and scope of oxazolone-mediated enetype reactions, 1,3-dipolar cycloadditions, and a novel Claisen-type rearrangement. The utility of these reactions towards natural product synthesis is described.