Conformational studies of peptides: Crystal and molecular structures of L ‐3,4‐dehydroproline and its t ‐butoxycarbonyl and acetyl amide derivatives

The crystal structures of L ‐3,4‐dehydroproline, t ‐butoxycarbonyl‐ L ‐3,4‐dehydroproline amide, and acetyl‐ L ‐3,4‐dehydroproline amide have been determined. L ‐3,4‐Dehydroproline is orthorhombic with a = 16.756, b = 5.870, c = 5.275 Å, and Z = 4; t ‐butoxycarbonyl‐ L ‐3,4‐dehydroproline amide is orthorhombic with a = 6.448, b = 8.602, c = 21.710 Å, and Z = 4; acetyl‐ L ‐3,4‐dehydroproline amide is monoclinic with a = 4.788, b = 10.880, c = 7.785 Å, β = 105.25°, and Z = 2. The final R value for the L ‐3,4‐dehydroproline is 0.046 based on 529 reflections; for t ‐butoxycarbonyl‐ L ‐3,4‐dehydroproline amide, 0.050 based on 792 reflections; and for acetyl‐ L ‐3,4‐dehydroproline amide, 0.058 based on 632 reflections. The structures clearly establish that the free amino acid exists in the zwitterionic form in the crystalline state. The molecular conformations of the t ‐Boc and acetyl derivatives consist of two planes: one involving the primary amide and the other the remaining atoms of the molecule. The acetyl‐ L ‐3,4‐dehydroproline amide contains a tertiary amide bond in the cis conformation. To the best of our knowledge, this is the first example of a cis bond in an acetyl derivative of an amino acid or peptide. At variance with the previously reported proline amides, which present ϕ and ψ values corresponding to those of a right‐handed α‐helical conformation (conformation A), the t ‐Boc and acetyl derivatives both have ϕ and ψ values corresponding to a collagenlike conformation (conformation F).