Steroids NOESY

Generally, the most powerful method for stmctural elucidation of steroids is nuclear magnetic resonance (nmr) spectroscopy. There are several classical reviews on the one-dimensional (1-D) proton H-nmr spectroscopy of steroids (267). C-nmr, a technique used to observe individual carbons, is used for stmcture elucidation of steroids. In addition, C-nmr is used for biosynthesis experiments with C-enriched precursors (268). The availability of higher magnetic field instmments coupled with the arrival of 1-D and two-dimensional (2-D) techniques such as DEPT, COSY, NOESY, 2-D J-resolved, HOHAHA, etc, have provided powerful new tools for the stmctural elucidation of complex natural products including steroids (269). 

C-21 methyl protons. The C-3 and C-16 melhine protons appeared at 8 3.82 and 4.99, respectively. The downfield chemical shift values of C-3 and C-6 methine protons were indicative of the presence of geminal oxygen functionahties. The C-6 resonated at 8 5.36 while the sp hybridized C-28 methylene protons resonated as two singlets, integrating for one proton each, at 8 5.56 and 6.06. A combination of H and C-NMR spectral data indicated to us that compound 11 has a steroidal skeleton. A detailed interpretation of broad C-NMR and DEPT spectra revealed the presence of three metlyl, ten methylene, eight methine and five quaternary carbon atoms in 11. The stereochemistry at various chiral centers was estabhshed with the aid of NOESY spectrum. 

Figure 6J8 (a) The chromatogram from a 0.75 mg injection of an impure steroidal drug substance. Peaks 1-5 are at levels of 2-3% each. The individual peaks were stored in BPSU loops, (b) NMR spectra were acquired with NOESY presaturation with an acquisition time of 10 h on a Bruker DRX500 fitted with a 4-mm SEl z-gradient EC probe with a 120 pi active cell volume. 

Fig. 7 Aliphatic region of a NOESY spectrum of dutasteride in DMSO-d6- Correlations show through space interactions between neighboring nuclei and are used to make relative stereochemical assignments for proton resonances. Correlations between the His methyl group and nearby protons on the same side of the steroid ring system are highlighted. (See Fig. 10 for structure and numbering scheme.)...

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