ABSTRACT
Conioidine A (1), isolated in 1993 with unknown relative and absolute configuration, was suggested to be a DNA-binding compound by an indirect technique. Four stereoisomers of conioidine A have been synthesized from d- and l-proline, and the natural product has been identified as possessing (4R,6R) absolute configuration. Binding of the conioidine diastereomers to calf thymus DNA (CT DNA) and human serum albumin (HSA) has been investigated by fluorescence spectroscopy and isothermal titration calorimetry (ITC). All stereoisomers display at least an order of magnitude weaker binding to DNA than the control compound netropsin; however, a strong association with HSA was observed for the (4R,6S) stereoisomer.
Subject(s)
Pyrrolidines/chemistry , Pyrrolidines/chemical synthesis , Solanaceous Alkaloids/chemistry , Solanaceous Alkaloids/chemical synthesis , Binding Sites , Binding, Competitive/drug effects , Calorimetry , Circular Dichroism , DNA/chemistry , Ethidium , Molecular Docking Simulation , Molecular Structure , Netropsin/chemistry , Netropsin/metabolism , Proline/chemistry , Serum Albumin, Human/chemistry , Spectrometry, Fluorescence , StereoisomerismABSTRACT
Oxidative cleavage of cycloalkenylalkylphosphonates 1 followed by treatment with base gives rise to homologated cycloalkenones 2 in good to excellent yields. Subjecting cycloalk-2-enylphosphonates 3 to identical conditions provides the one-carbon ring-contracted compounds 4 in excellent yields. Oxidative cleavage of γ,δ-unsaturated ketophosphonates 6 followed by treatment with base affords 2-cyclopenten-1-ones 7 in good overall yields. This method may offer a practical alternative to existing methods for effecting one-carbon ring expansion, ring contraction, and annulation reactions.
