[Nitrogen pyramidal amides and related compounds].
A planar amide bond is a fundamental linkage in the structures of peptides and proteins. The rigid planarity of the amide linkage, due to a conjugation between carbonyl and amine groups, may be requisite for encoded protein folding and many other biological processes. Non-planar amides in the ground state will decode the significance of the planarity and rigidity of the amide linkage. We show here that simple amides of 7-azabicyclo[2.2.1]heptane, free from steric bias, including parent N-benzoyl 7-azabicyclo[2.2.1]heptane, are nitrogen-pyramidal amides in the crystalline state. We can suggest that pyramidalized amide nitrogen is a general feature and intrinsic to the 7-azabicyclo[2.2.1]heptane motif. Low rotational barriers of the amide C-N bond in a series of N-benzoyl amides of 7-azabicyclo[2.2.1]heptane, compared to monocyclic amides, may imply that ground-state nitrogen pyramidalization of the former amides also exist in solution. The 7-azabicyclo[2.2.1]heptane motif also favors nitrogen pyramidalization of sulfonamides and N-nitrosoamines, which can lead to pharmacophores after appropriate modification.
Ohwada
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Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603 Japan.
D000577:Amides / Q000737:chemistry*; D002625:Chemistry, Organic; D003460:Crystallization; D006536:Heptanes / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry*; D009602:Nitrosamines / Q000737:chemistry; D055601:Organic Chemistry Phenomena; D012996:Solutions; D013449:Sulfonamides / Q000737:chemistry
D000577:Amides; D006536:Heptanes; D009602:Nitrosamines; D012996:Solutions; D013449:Sulfonamides; D009584:Nitrogen