A phenyl-substituted chiral dihydrofuroangelicin, 4-methyl-8-(2-E-phenylethenyl)-8,9-dihydro-2H-furo[2,3-h]- 1-benzopyran-2-one, synthesized in racemic form, has been resolved by HPLC chiral separation, and its absolute configuration determined by the non-empirical exciton chirality method. The solution conformation has been investigated through NMR and molecular modeling methods: two minima found by molecular mechanics and DFT methods are in keeping with observed 1H-1H 3J coupling constants and NOE effects. The experimental CD spectrum for the second eluted enantiomer shows a positive couplet between 230 and 350 nm (amplitude A = + 15.7); by application of the exciton chirality method, the absolute configuration of this enantiomer at C8 is determined as (S). The experimental spectrum is in very good agreement with the one evaluated by means of DeVoe coupled-oscillator calculations, using the DFT calculated geometries.
Enantiomer separations by HPLC using the macrocyclic glycopeptides teicoplanin (Chirobiotic T), teicoplanin aglycon (Chirobiotic TAG), and ristocetin A (Chirobiotic R) chiral stationary phases (CSP) have been achieved on a unique series of potentially biologically active racemic analogues of dihydrofurocoumarin. The macrocyclic glycopeptides have proven to be very selective for this class of compound. All of the 28 chiral analogues examined afforded baseline separation on at least one of the macrocyclic glycopeptide CSP. The teicoplanin CSP showed the broadest enantioselectivity with 24 of the compounds baseline separated. The TAG and the R CSP produced 23 and 14 baseline separations respectively. All three mobile phase modes, i.e. normal phase (NP), reversed phase (RP), and new polar organic modes (PO), have been evaluated. The NP mode proved to be most effective for the separation of chiral dihydrofurocoumarins on all CSP tested. In the reversed phase (RP) mode, all three CSP separated a similar number of compounds. It was observed that the structural characteristics of the analytes and steric effects are very important factors leading to chiral recognition. Hydrogen bonding was found to play a secondary role in chiral discrimination in the normal phase and polar organic modes. Hydrophobic interactions are important for chiral separation in the reversed-phase mode. Chromatographic retention data does not provide information on the absolute configuration of these chiral dihydrofurocoumarin derivatives. However, when coupled with circular dichroism using the exciton coupling chirality method, the enantiomer elution order and the absolute configuration of some chiral dihydrofurocoumarins were successfully determined.
The palladium-catalyzed annulation of 1,3-dienes by o-iodoaryl acetates provides an efficient approach to biologically interesting dihydrobenzofurans. The annulation is believed to proceed via (1) oxidative addition of the aryl iodide to Pd(0), (2) syn-addition of the resulting arylpalladium complex to the 1,3-diene, (3) intramolecular coordination of the phenolic oxygen to the Pd center, (4) hydrolysis of the acetyl group, and (5) reductive elimination of Pd(0), which regenerates the catalyst. This reaction is quite general, regioselective, and stereoselective, and a wide variety of terminal, cyclic, and internal 1,3-dienes, as well as electron-rich and electron-deficient o-iodoaryl acetates, can be utilized.
[reaction: see text] A variety of biologically interesting dihydrofurocoumarins have been synthesized in high yields by the palladium-catalyzed annulation of 1,3-dienes by o-iodoacetoxycoumarins. This reaction is very general and regioselective, and a wide variety of terminal, cyclic, and internal 1,3-dienes can be utilized.
Abstract:We have developed novel fluorogenic transformations based on formation of C À C bonds catalyzed by palladium using iodocoumarin 1 as a model aryl iodide, where fluorescence is quenched completely due to effects of the heavy, polarizable iodine atom. Substitution of the iodine atom for the carbon using Sonogashira, Suzuki-Miyaura and Heck couplings results in a dramatic fluorescence enhancement. This approach has been used successfully for the optimization of reaction conditions and kinetic studies in high throughput format.
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