Scalable and chromatography-free synthesis of 2-(2-formylalkyl)arenecarboxylic acid derivatives through the supramolecularly controlled hydroformylation of vinylarene-2-carboxylic acids

This protocol describes how to prepare 2-(2-formylalkyl)-arenecarboxylic acid derivatives, common building blocks for the synthesis of various valuable chemicals (e.g., anti-obesity and Alzheimer's disease treatment pharmaceuticals), by using the fully regioselective hydroformylation of vinyl arene derivatives. This catalytic reaction proceeds cleanly with 100% regioselectivity and chemoselectivity. The procedure is reliably scalable and can be efficiently conducted on a multigram scale. The analytically pure product is easily isolated with a nearly quantitative yield by using a simple acid-base extraction workup and avoids any tedious chromatography. This protocol details the synthesis of a bisphosphite ligand (L1) that is a pivotal element of the catalytic system used, Rh(acac)(CO)(2) with ligand L1, starting from commercial building blocks. The protocol also describes a general procedure for the preparative hydroformylation of vinylarene-2-carboxylic acid derivatives to 2-formylalkylarene products, providing a representative example for the hydroformylation of 2-vinylbenzoic acid (1a) to 2-(3-oxopropane)-benzoic acid (2a). The synthesis of L1 (six chemical reactions) uses 2-nitrophenylhydrazine, 4-benzyloxybenzoylchloride and (S)-binol, and takes 5-7 working days. The actual hydroformylation reaction of each vinyl arene derivative takes similar to 4 h of active effort over a period of 1-3 d

A global view of the proteome perturbations by Hsp90 inhibitors

Heat shock protein 90 (Hsp90) is a highly efficient molecular chaperone and a major hub in the protein network that maintains cellular homeostasis and function. The qualitative and quantitative changes and rewiring of this protein network in tumor cells make them vastly dependent on Hsp90, which therefore becomes a key target to fight cancer. The inhibition of Hsp90 creates a profound transformation in the cell proteome. In this chapter, we review and analyze the most recent efforts that take advantage of the druggability of Hsp90 in order to understand the global changes at the proteome level that this inhibition produces. The considerable impact that the targeting of Hsp90 has on the structure of these protein networks is also discussed