Browsing publications of the department medicinal chemistry (MCH) by Journal
Now showing items 1-4 of 4
Desymmetrization of C -Symmetric Bis(Boronic Esters) by Zweifel Olefinations.anti-Configured 1,3-dimethyl deoxypropionate motifs are important sub structures in natural products. Herein, we describe a bidirectional approach for the rapid construction of natural products featuring such motifs by using C2 -symmetrical 1,3-bis(boronic esters). As for its application in convergent syntheses it was important to establish a selective mono-Zweifel olefination we describe the scope and limitations by using different 1,3-bis(boronic esters) and nucleophiles. This protocol takes advantage of the combination of the Hoppe-Matteson-Zweifel chemistry, which was elegantly put into practice by Aggarwal et al. In order to show its applicability the total syntheses of two natural products, serricornin and (+)-invictolide, were performed.
Resolving Inflammation: Synthesis, Configurational Assignment, and Biological Evaluations of RvD1.New drugs that can resolve inflammation without immunosuppressive effects are at the medicinal chemistry frontier. Pro-resolving endogenously formed small molecules, that is, the resolvins, are excellent candidates displaying such bioactions. The first total synthesis of the specialized pro-resolving mediator RvD1n-3 DPA has been achieved using the underutilized sp3 -sp3 Negishi cross coupling reaction and an alkyne hydrosilylation-protodesilylation protocol. Biological evaluations revealed that this novel mediator displays low nanomolar pro-resolving properties and potently activates the human DRV1/GPR32 receptor. As such, this endogenous natural product is a lead compound for the development of novel immunoresolvents.
Synthesis of Desepoxy-Tedanolide C.The synthesis of desepoxy-tedanolide C was accomplished and provided experimental evidence on the configuration of tedanolide C. The reported chemical shifts and coupling constants point to a configuration different from the published structure and analogous to the structures of the other members of this family of natural products. The key step is a Kiyooka aldol protocol for the stereoselective synthesis of the tertiary alcohol flanked by three additional oxygenated carbon atoms. Furthermore, two additional aldol reactions and a Julia-Kocienski olefination were used to assemble the carbon framework.
Total Synthesis and Structure Revision of Halioxepine.The first total synthesis of halioxepine is accomplished using a 1,4-addition for constructing the quaternary center at C10 and a halo etherification for the generation of the tertiary ether at C7. The correct structure of halioxepine was determined by assembling different enantiomeric building blocks and by changing the relative configuration between C10 and C15.