Evolution of a Strategy for Concise Enantioselective Total Synthesis of the Salinosporamide Family of Natural Products

Abstract

Our first strategy for rapidly accessing pyrrolidinone cores of salinosporamides involved combined use of memory of chirality and dynamic kinetic resolution principles in aldol reactions of the serinederived 5-oxazolidinone substrate, which was ultimately unsuccessful with respect to enantioselectivity. This failure led us to the revised strategy. The influence of the stereocenter in 5-oxazolidinone enabled selective installation of the C-2 stereocenter. The intramolecular aldol reaction of the C-2 stereodefined aldol substrate was successful. An unexpected hydrolytic dynamic kinetic resolution was observed in hydrolyses of the bicyclic aldol products. This unprecedented substratedriven hydrolytic dynamic kinetic resolution was utilized in preparing the pyrrolidinone core with excellent efficiency. Through this strategy, the concise total syntheses of salinosporamides A and B as well as cinnabaramides A, E, and F were achieved with high selectivity.

Nitrogen monoxide and calix[4]pyrrolato aluminate: structural constraint enabled NO dimerization

“…1C, VIII) exhibiting similar redox chemistry compared to transition metal nitrosyl complexes. 41,42 Despite this plethora of examples, studies on element-ligand cooperative binding of NO different from FLP-type reactions are rare.…”