5,5-Dimethylthiazolidine-4-carboxylic acid (DTC) as a proline analog with restricted conformation.
Spectroscopic evidence is presented for the lack of intramolecular hydrogen bonding in a simple peptide derivative of 5,5-dimethylthiazolidine-4-carboxylic acid (Dtc). The infrared spectrum of Boc-Pro-Ile-OMe 1 in nonpolar solvents displays two N-H stretching bands at 3419 and 3330 cm-1 in CCl4 and one at 3417 and 3328 cm-1 in CHCl3. The low frequency band at 3328-3330 cm-1 may be assigned to conformations with an intramolecular hydrogen bond between the Ile N-H and Boc C = O. The band at 3417-3419 cm-1 is the normal Ile N-H stretch. In the polar solvent CH3CN only one NH stretching band at 3365 cm-1 is observed. The IR spectrum of Boc-Dtc-Ile-OMe 2, on the other hand, displays one N-H stretching band at 3423 cm-1 in CCl4 and one at 3418 cm-1 in CHCl3. The IR spectrum of 2 does not display the N-H stretching band that would arise from intramolecular hydrogen bonding between the Boc C = O and Ile N-H. The lack of intramolecular hydrogen bonding for Boc-Dtc-Ile-OMe 2 was evident also in the NMR spectra in nonpolar solvents. The 1H-NMR spectrum of the Pro dipeptide 1 in 50% CDCl3/C6D6 at 20 degrees displayed two Ile-NH signals at 6.58 and 7.74 ppm. The latter signal corresponds to the intramolecularly hydrogen bonded Ile-NH in the trans-Boc isomer of 1 (60% of the total population), while the former signal corresponds to the nonhydrogen bonded Ile-NH in the cis-Boc isomer.(ABSTRACT TRUNCATED AT 250 WORDS)
Samanen
J
J
Smith Kline and French Laboratories, King of Prussia, PA.
Zuber
G
G
Bean
J
J
Eggleston
D
D
Romoff
T
T
Kopple
K
K
Saunders
M
M
Regoli
D
D
D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D010455:Peptides / Q000032:analysis* / Q000138:chemical synthesis; D011392:Proline; D011487:Protein Conformation; D013055:Spectrophotometry, Infrared; D013844:Thiazoles / Q000032:analysis*; D014961:X-Ray Diffraction
D010455:Peptides; D013844:Thiazoles; C065579:5,5-dimethylthiazolidine-4-carboxylic acid; D011392:Proline