Geometrical and conformational preferences of the 9-fluorenylmethoxycarbonyl-amino moiety

Structural parameters, originating from x-ray crystallographic data, have been compiled for 13 derivatives of amino acids, peptides and related compounds, which contain a total of 14 Fmoc-NH- moieties. For these moieties, molecular geometries and conformations - described by the omega(0), theta(1), theta(2) and theta(3') torsion angles - were analysed and compared with the corresponding parameters for the Z-NH- and Boc-NH-moieties (290 and 553, respectively). To gain a deeper insight into the conformational features of the Fmoc-NH- moiety, ab initio free molecule calculations were performed for fully relaxed minima. Also the potential energy surface as a function of the torsion angles (theta(3r), theta(2)) was generated. The conformational features of the Fmoc-NH- moiety: (i) two possible values for the angle omega(0) (similar to180degrees or, rarely, similar to0degrees) and (ii) the angle theta(1) = 180degrees +/- 15degrees, are common to the Z-NH- and Boc-NH- systems. By contrast, the theta(2) and theta(3) angles in the Fmoc, Z and Boc groups differ essentially. In the Fmoc groups 02 mostly has values of 180degrees +/- 30degrees and values up \115degrees\ seem to be forbidden, whereas fewer than half of the Z groups adopt theta(2) similar to 180degrees and the remainder have theta(2) in the range of \90degrees +/- 20degrees\. On the other hand, the Boc methyl groups are staggered. The theta(3) values observed for Fmoc are limited to the regions of 180degrees +/- 20degrees and \60degrees +/- 20degrees\, while for the Z group a variety of theta(3) occurs. The orientation of the fluorenyl vs the urethane function is mostly trans. Our results suggest a lower conformational flexibility for the Fmoc group compared with that of the Z group. Our calculations confirm that the observed conformational features for the Fmoc-NH- moiety are inherent properties. The Fmoc-NH-moiety in crystals involves the participation of its O=C-NH functionality in hydrogen bonds. Copyright (C) 2004 European Peptide Society and John Wiley Sons, Ltd.