Proton NMR analyses, shielding mechanisms, coupling constants, and conformations in steroids bearing halogen, hydroxy, and oxo groups and double bonds

Frondoside A. A novel triterpene glycoside from the holothurian Cucumariafrondosa

“…Thus, since all the enhancements for C-16H arose for protons that are a , C-16H must also be assigned as a. Coupling constant calculations (1 1) for the C-16 proton with C-17Ha and the C-15 protons, based on a distorted envelope conformation for the D-ring, again supported the P configuration for the C-16 acetoxy group (Table 2). Therefore, it appears that the presence of the pseudo-equatorial (P) C-16 substituent induces larger downfield shifts on the pseudo-equatorial C-15a and C-17ci vicinal protons, a situation analogous to the reported effect of substituents in cyclohexanoid systems (9).…”

Classical H-NMR shielding calculations with the program SHIFT and conformational analysis of three cyclophanes

“…The linear electric field effects (LEF ) due to the presence of C-halogen and C-hydroxy groups (the inducing C-X bonds) are calculated with Coulomb-type equations, describing the polarization of C-Y (C-C or C-H) bonds with the observed nucleus Y by application of point poles for the inducing C-X group; these were derived from published dipole moments and MO calculations and checked with more than 250 observed and calculated proton shifts in steroids 6 and decalins. 9 With a screening factor of 17.8 ppm esu 1 for protons (corresponding to the Lamb term) and 170 ppm esu 1 for carbon signals, 10 the observed shifts are usually reproduced to within š0.1 ppm for 1-H 6 and š1 ppm for carbon atoms remote from high-order distortions 11 (see below).…”

“…in steroids with an X-Y distance >10Å) were correctly reproduced. 12 Anisotropy effects generated by single bonds with a diversity of published susceptibility values were found to be misleading 6,13 and are neglected.…”

“…in gauche fragments; 16 in SHIFT they are calculated (abbreviated grache) with a modified 2 in the default option the point of action is used arising from the center of the C X bond when X D C and at a distance of 20% from X when X is not C. Parametrizations close to the original ones 3,4 were found to predict 1 H shielding variations by C O groups within š0.1 ppm for over 20 signals in three different steroids, if simultaneously the strong LEF contribution of the C O dipole was taken into account. 6 The program also provides for  evaluations with C C double and and C C triple bonds, although the experimental basis set in this case is smaller.…”

“…The advent of 2D NMR methods made it possible to use, e.g., with a single monosubstituted androstane 26 non-equivalent signals for parametrizations. 6 For the parametrization of the computer program realistic structures were used from force field minimizations, which were checked as far as possible against published x-ray analyses.…”