Rapid acquisition of1H-13C and1H-15N heteronuclear chemical shift correlation data at the submilligram level using SMIDG (submicro inverse-detection gradient) NMR probe technology

The application of submicro inverse-detection gradient (SMIDG) NMR probe technology at 600 MHz is demonstrated for the rapid acquisition of both 1H–13C and 1H–15N heteronuclear chemical shift correlation data. Using a 750 µg (ca 1.5 µmol, MW 505) sample of the complex spirononacyclic alkaloid cryptospirolepine, the acquisition of 1H–13C direct correlation GHSQC data is possible as rapidly as 34 s. Fully resolved GHSQC data are accessible in < 5 min. The acquisition of well digitized 1H–13C long-range heteronuclear shift correlation data (GHMBC) in 16 min is demonstrated. The acquisition of 1H–15N direct heteronuclear shift correlation data at natural abundance with ca 15 : 1 signal-to-noise ratio is possible in < 50 min despite the inherently much lower sensitivity of 15N relative to 13C as a structural probe. Finally, long-range correlations to three of the four nitrogens in the alkaloid are identified in a 1H–15N long-range (GHMBC) spectrum acquired overnight. The ability to characterize rapidly the chemical structures of submilligram sample quantities using rigorous heteronuclear shift correlation methods realistically offers the possibility of employing heteronuclear correlation techniques for the first time in the characterization of compounds with limited solution stability at the submilligram level.