Rapid acquisition of H-1-C-13 and H-1-N-15 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 te chnology at 600 MHz is demonstrated for the rapid acquisition of both H-1-C -13 and H-1-N-15 heteronuclear chemical shift correlation data. Using a 750 mu g (ca 1.5 mu mol, MW 505) sample of the complex spirononacyclic alkaloi d cryptospirolepine, the acquisition of H-1-C-13 direct correlation GHSQC d ata is possible as rapidly as 34 s. Fully resolved GHSQC data are accessibl e in <5 min. The acquisition of well digitized H-1-C-13 long-range heteronu clear shift correlation data (GHMBC) in 16 min is demonstrated. The acquisi tion of H-1-N-15 direct heteronuclear shift correlation data at natural abu ndance with ca 15:1 signal-to-noise ratio is possible in <50 min despite th e inherently much lower sensitivity of N-15 relative to C-13 as a structura l probe. Finally, long-range correlations to three of the four nitrogens in the alkaloid are identified in a H-1-N-15 long-range (GHMBC) spectrum acqu ired overnight. The ability to characterize rapidly the chemical structures of submilligram sample quantities using rigorous heteronuclear shift corre lation methods realistically offers the possibility of employing heteronucl ear correlation techniques for the first time in the characterization of co mpounds with limited solution stability at the submilligram level. Copyrigh t (C) 1999 John Wiley & Sons, Ltd.