ABSTRACT
The fungal metabolite TAN-2483B has a 2,6-trans-relationship across the pyran ring of its furo[3,4-b]pyran-5-one core, which has thwarted previous attempts at its synthesis. We have now developed a chiral pool approach to this core and prepared side-chain analogues of TAN-2483B. The synthesis relies on ring expansion of a reactive furan ring-fused dibromocyclopropane and alkynylation of the resulting pyran. The furan ring is constructed by palladium-catalysed carbonylative lactonisation. Various side-chains are appended through Wittig-type chemistry. The prepared analogues showed micromolar activity towards cancer cell lines HL-60, 1A9 and MCF-7 and certain human disease-relevant kinases, including Bruton's tyrosine kinase (Btk).
Subject(s)
Antineoplastic Agents/chemical synthesis , Lactones/chemistry , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/chemical synthesis , Pyrans/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Lactones/chemical synthesis , Lactones/pharmacology , Molecular Structure , Phosphotransferases/antagonists & inhibitors , Phosphotransferases/metabolism , Protein Kinase Inhibitors/pharmacology , Pyrans/chemical synthesis , Pyrans/pharmacology , Structure-Activity RelationshipABSTRACT
The reductions in the transmission of emission originating from a fluorophore dissolved in a polymer matrix due to light scattering were compared in two forms of planar waveguides used as luminescent solar concentrators: a thin film of poly(methylmethacrylate) (PMMA) spin-coated on a glass plate and a solid PMMA plate of the same dimensions. The losses attributable to light scattering encountered in the waveguide consisting of the thin film of polymer coated on a glass plate were not detectable within experimental uncertainty, whereas the losses in the solid polymer plate were significant. The losses in the solid plate are interpreted as arising from light-scattering centers comprising minute bubbles of vapor/gas, incomplete polymerization or water clusters that are introduced during or after the thermally induced polymerization process.
