Theoretical and experimental conformational analysis of two diastereomeric "Val"-statine derivatives.
The preferred conformations and self-association modes of the two diastereomeric N-acetyl, methylamides of 3-hydroxy, 4-amino, 5-methylhexanoic acid ("Val"-statine) with (S,S) and (R,S) configurations at the 3-hydroxy and 4-amino carbon atoms, respectively, were determined in solution as well as in the crystal state by infrared absorption, 1H nuclear magnetic resonance and x-ray diffraction. A corollary conformational energy computation study was also carried out. In the crystal state intramolecular H-bonds are absent in both structures. However, the change in chirality of the carbon atom carrying the hydroxy group and the presence of a co-crystallized water molecule in the (S,S) isomer induce partially different backbone and "Val" side chain conformations and divergent intermolecular H-bonding schemes in the two isomers. A marked propensity to self-aggregate is seen in solvents of low polarity. The two isomers, however, are largely solvated in solvents of high polarity. Conformational energy computations indicate that in vacuo both diastereomers exhibit a significant flexibility and the conformers presenting absolute minima are not stabilized by any intramolecular bonding.
Toniolo
C
C
Department of Organic Chemistry, University of Padova, Italy.
Valle
G
G
Crisma
M
M
Bonora
G M
GM
Lelj
F
F
Cristinziano
P L
PL
Barone
V
V
Nisato
D
D
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012996:Solutions; D013237:Stereoisomerism; D014633:Valine / Q000737:chemistry*; D014961:X-Ray Diffraction
D000596:Amino Acids; D012996:Solutions; D014633:Valine; C013165:statine