A stereoselective synthetic entry point to the 5-8-5 carbocyclic core of the ophiobolins was developed. This strategy exploits the chiral tertiary alcohol of ophiobolin A to guide assmebly of the 5-8-5 scaffold in a single step via a photoinitiated cycloisomerization. Mechanistic insights into the origin of stereocontrol in this reaction are described, as are efforts to elaborate the resultant fused 5-8-5 ring system to the pharmacophore of ophiobolin A.
View Article and Find Full Text PDFA new polyene cyclization strategy exploiting β-ionyl derivatives was developed. Photoinduced deconjugation of the extended π-system within these chromophores unveils a contrathermodynamic polyene that engages in a Heck bicyclization to afford [4.4.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
June 2021
Methyl groups are ubiquitous in biologically active molecules. Thus, new tactics to introduce this alkyl fragment into polyfunctional structures are of significant interest. With this goal in mind, a direct method for the Markovnikov hydromethylation of alkenes is reported.
View Article and Find Full Text PDFA 5-8-5 carbocyclic ring system forms the core of over 30 distinct natural products. Several members of this family have gained attention for their diverse activity in cell culture. In these cases, biological function is mediated by the arrangement of substituents around a conserved 5-8-5 nucleus.
View Article and Find Full Text PDFMetallo prodrugs that take advantage of the inherent acidity surrounding cancer cells have yet to be developed. We report a new class of pH-activated metallo prodrugs (pHAMPs) that are activated by light- and pH-triggered ligand dissociation. These ruthenium complexes take advantage of a key characteristic of cancer cells and hypoxic solid tumors (acidity) that can be exploited to lessen the side effects of chemotherapy.
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