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The synthesis and analysis of the conformation in solution of the dolastatin 3 diastereomer cyclo[‐ L ‐Pro‐ L ‐Leu‐ D ‐(Gln)Thz‐(Gly)Thz‐ L ‐Val‐]
Author(s) -
Bredenkamp Martin W.,
Holzapfel Cedric W.,
van Zyl Wynand J.
Publication year - 1990
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.1990199001163
Subject(s) - chemistry , diastereomer , intramolecular force , peptide , stereochemistry , cyclic peptide , nuclear magnetic resonance spectroscopy , spectroscopy , hydrogen bond , peptide bond , thiazole , circular dichroism , amino acid , molecule , crystallography , organic chemistry , physics , biochemistry , quantum mechanics
The cyclic peptide cyclo[‐ L ‐Pro‐ L ‐Leu‐ D ‐(Gln)Thz‐(Gly)Thz‐ L ‐Val‐] ( 1a ), which is a diastereomer of the antineoplastic agent dolastatin 3 ( 1b ), and contains the unusual thiazole amino acids, was synthesized. All the peptide bonds of the cyclic peptide 1a are trans in solution, and the compound is conformationally homogeneous, as deduced by CD spectroscopy and comprehensive NMR spectroscopy. The conformation was refined by SYBYL molecular force‐field calculations. The saddle‐like conformation contains three intramolecular, but no transannular hydrogen bonds.