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

6533b838fe1ef96bd12a4685

RESEARCH PRODUCT

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

Liliana Mazur Anna E. Koziol Małgorzata A. Broda Barbara Rzeszotarska

subject

crystal structure Stereochemistry Ab initio Molecular Conformation Crystal structure Crystallography X-Ray Biochemistry Boc amino protection Structure-Activity Relationship fluorene Structural Biology Ab initio quantum chemistry methods Drug Discovery Molecule Moiety urethane geometry Fmoc amino protection Amino Acids Molecular Biology Pharmacology Fluorenes Molecular Structure Chemistry Hydrogen bond ab initio calculations Organic Chemistry Hydrogen Bonding General Medicine Z amino protection Molecular geometry Potential energy surface Molecular Medicine Crystallization Peptides N‐terminally protected peptides

description

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 omegao, theta1, theta2 and theta3' 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 (theta3', theta2) was generated. The conformational features of the Fmoc-NH- moiety: (i) two possible values for the angle omegao (approximately 180 degrees or, rarely, approximately theta degrees) and (ii) the angle theta1 = 180 degrees +/- 15 degrees, are common to the Z-NH- and Boc-NH- systems. By contrast, the theta2 and theta3 angles in the Fmoc, Z and Boc groups differ essentially. In the Fmoc groups theta2 mostly has values of 180 degrees +/- 30 degrees and values up [115 degrees] seem to be forbidden, whereas fewer than half of the Z groups adopt theta2 approximately 180 degrees and the remainder have theta2 in the range of [90 degrees +/- 20 degrees]. On the other hand, the Boc methyl groups are staggered. The theta3 values observed for Fmoc are limited to the regions of 180 degrees +/- 20 degrees and 160 degrees +/- 20 degrees], while for the Z group a variety of theta3 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.

year	journal	country	edition	language
2004-08-10	Journal of Peptide Science

10.1002/psc.555 https://onlinelibrary.wiley.com/doi/abs/10.1002/psc.555