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 ω 0 , θ 1 , θ 2 and θ 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 (θ 3′ , θ 2 ) was generated. The conformational features of the Fmoc‐NH– moiety: (i) two possible values for the angle ω 0 (∼180° or, rarely, ∼0° ) and (ii) the angle θ 1 = 180° ± 15°, are common to the Z‐NH– and Boc‐NH– systems. By contrast, the θ 2 and θ 3 angles in the Fmoc, Z and Boc groups differ essentially. In the Fmoc groups θ 2 mostly has values of 180° ± 30° and values up |115°| seem to be forbidden, whereas fewer than half of the Z groups adopt θ 2 ∼ 180° and the remainder have θ 2 in the range of |90° ± 20°|. On the other hand, the Boc methyl groups are staggered. The θ 3 values observed for Fmoc are limited to the regions of 180° ± 20° and |60° ± 20°|, while for the Z group a variety of θ 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 OC–NH functionality in hydrogen bonds. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.