Total Synthesis of the Turrianes and Evaluation of Their DNA‐Cleaving Properties

摘要: The first total synthesis of three naturally occurring cyclophane derivatives belonging to the turriane family natural products is described. Their sterically hindered biaryl entity formed by reaction Grignard reagent derived from aryl bromide 10 with oxazoline derivative 18, and macrocyclic tether targets efficiently forged ring closing metathesis. While conventional RCM catalyzed ruthenium-carbene complexes 33 or 34 invariably leads formation mixtures both stereoisomers undesirable (E)-alkene prevailing, alkyne metathesis (RCAM) followed Lindlar reduction resulting cycloalkynes 37 38 opens a convenient stereoselective entry into this class compounds. RCAM can either be accomplished using tungsten alkylidyne complex [(tBuO)3 [triple bond] WCCMe3] means catalyst in situ [Mo(CO)6] para-trifluoromethylphenol. latter method significantly accelerated when carried out under microwave heating. Furthermore, judicious choice protecting groups for phenolic -OH functions turned crucial. PMB-ethers were found compatible diverse conditions en route 3-5; their cleavage, however, had carefully optimized minimize competing O-C PMB migration. Turrianes 3-5 are shown potent DNA cleaving agents oxidative administered presence copper ions.