Indolo quinolizidine conformations

Conformational study of geissoschizine isomers and their model compounds (geissoschizine is the indolo[2,3-fl]quinolizidine derivative considered to be an important participant of indole alkaloids biogenesis) 99H(51)649. 

In comparison with other spectroscopic methods, 13C-NMR spectroscopy affords the most valuable information for the stereochemical and conformational analysis of quinolizidine compounds. On the basis of the results, summarized in a review by Tourwe and van Binst (313) as well as in a series of publications (314-318), the steric structure elucidation of indolo[2,3-a]quinolizidine alkaloids has been facilitated. 

The nature of the ring fusion in quinolizidine derivatives may be determined from the 15N chemical shifts, which are to lower field in the transfused derivatives. This is shown for the indolo[a]quinolizidines 73 and 74 (chemical shifts to low field of external anhydrous liquid ammonia)115 and by the perhydropyrido[l,2-c][l,3]thiazines 8 66.9 trans conformer 312, 8 43.9 S-inside cis conformer 313.ll5a... 

Indolo or benzo fusion at the 5,6-position in perhydropyrido[l,2-c]pyrim-idine (335-340) (Fig. 13), as in 360 and 361 shifts the equilibrium in favor of the cis-fused conformer 364 and the axial JV-methyl trans-fused con-former 362, with 54% of the equatorial iV-methyl trans-fused conformer 363 present at room temperature (CDC13 solution).284 285 The shift in equilibrium (compare corresponding shift for 192-194 compared to quinolizidine 179-181, Section III,B,3) is presumably a result of a destabilization of 362 and 363 by the peri-type interaction involving the C-l-H and either the... 

The different conformations of indolo[2,3-a]quinolizidines play an important role in predicting the thermodynamically more stable epimer (see below). The indolo[2,3-a]quinolizidine system can exist in three main conformations one C/D trans ring juncture (conformation a) and two C/D cis ring junctures (conformations b and c). These are in equilibrium by nitrogen inversion and cw-decalin type ring interconversion. Ring C is considered to be in a half chair conformation and ring D in a chair conformation, Scheme (16) [40]. 

The stability of indolo[2,3-a]quinolizidine epimers can be determined by conformational analysis, bearing in mind three important factors ... 

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