Download or read book Synthesis of a Proteasome Inhibitor Containing a [Gamma]-lactam-[Beta]-lactone Fused Ring System written by Armando Urbina and published by . This book was released on 2009 with total page 81 pages. Available in PDF, EPUB and Kindle. Book excerpt: Natural proteasome inhibitors such as omuralide and salinosporamide A exhibit potent cancer cell cytotoxicity, through selective inhibition of the 20S proteasome. Recently, the mechanism of resistance to salinosporamide A was proposed by Moore (UCSD, SIO) based on gene analysis of sediment bacteria Salinospora which produces the compound. In this research, initial design and the synthesis of salinosporamide A-resistant proteasome inhibitor is demonstrated. It features a stereoselective Ugi 4-center 3-component condensation reaction of [Gamma]-ketoacid with novel convertible isocyanides. This forms a functionalized pyroglutamic acid, and further manipulations afford the fused [Gamma]-lactam-[Beta]-lactone core bicyclic ring of the natural product, which is essential to the action of the inhibition.