Cyclopeptide alkaloids. Conformational analysis of the dihydro-p-phencyclopeptine nucleus

Journal Article · Wed Feb 23 04:00:00 EST 1983 · J. Am. Chem. Soc.; (United States)

DOI:https://doi.org/10.1021/ja00342a064· OSTI ID:6263270

Lagarias, J C ^[1]; Yokoyama, W H; Bordner, J; Shih, W C; Klein, M P; Rapoport, H

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1. Univ. of California, Davis

A combined NMR spectroscopic and x-ray crystallographic approach to the analysis of the conformations of two synthetic dihydro-p-phencyclopeptines, (5S)-5,6-trimethylene-8-deamino-1,2-dihydro-p-phencyclopeptine (2d) and its N-methyl derivative, (5S)-3-methyl-5,6-trimethylene-8-deamino-1,2-dihydro-p-phencyclopeptine (2a), is described. The one-dimensional /sup 1/H NMR spectra of both cyclopeptides are assigned by means of two-dimensional homonuclear (/sup 1/H) J-spectral analysis, homonuclear decoupling experiments, computer-generated spectral simulations, and steady-state /sup 1/H NOE measurements at 270 and 360 MHz. On the basis of Karplus relationships derived from these experimental results, together with /sup 13/C NMR spectroscopic analysis, predictions for the solution conformations of both cyclopeptides are deduced. The solution conformation of the N-methyl cyclopeptide 2a is compared with its solid-state conformation determined by x-ray crystallography, and the two are found to be in good agreement. Comparative NMR studies of the two p-phencyclopeptines reveal only subtle conformational differences between the two cyclopeptides. These differences occur in the region near the N3-C4 amide where the structural difference between the two cyclopeptides, the N-methyl group, is localized. Of the eight possible conformations of the p-phencyclopeptine nucleus, both cyclopeptides adopt the same overall geometry with both amides trans. The small conformational differences that do exist between 2a and 2d reflect the ability of NH cyclopeptide 2d to form an intramolecular hydrogen bond similar to those observed in the ..gamma.. turns in proteins. Conformational implications with respect to ion binding of the p-phencyclopeptines nucleus are considered.

• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 6263270
• Journal Information: J. Am. Chem. Soc.; (United States), Journal Name: J. Am. Chem. Soc.; (United States) Vol. 105:4; ISSN JACSA
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400301* -- Organic Chemistry-- Chemical & Physicochemical Properties-- (-1987)
550200 -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ALKALOIDS
COHERENT SCATTERING
DIFFRACTION
MAGNETIC RESONANCE
NUCLEAR MAGNETIC RESONANCE
ORGANIC COMPOUNDS
PEPTIDES
PROTEINS
RESONANCE
SCATTERING
SPECTRA
STRUCTURAL CHEMICAL ANALYSIS
X-RAY DIFFRACTION