Conformational Analysis of the Cyclic Pentadepsipeptide Cyclo(Tro‐Aib‐Aib‐Aib‐Aib) in the Solid State and in Solution

Abstract

The cyclic 16-membered pentadepsipeptide cyclo(Tro-Aib-Aib-Aib-Aib) (1) was crystallized from MeOH/ AcOEt/CH 2 Cl 2 , and its structure was established by X-ray crystallography (Fig. 1). There are two symmetryindependent molecules with different conformations in the asymmetric unit. Two intramolecular H-bonds stabilize two b-turns in each molecule. On the other hand, two of the four Aib residues are forced to assume a nonfavorable nonhelical conformation in each of the symmetry-independent molecules ( Table 1). The conformational study in CDCl 3 solution by NMR spectroscopy and molecular dynamics (MD) simulations indicate that the averaged structure (Fig. 3) is almost the same as in the solid state.

Synthesis of Enniatin‐like Cyclic Depsipeptides via ‘Direct Amide Cyclization’

“…Effective methods for the introduction of α,α-disubstituted α-amino acids and subsequent ring closure to give a cyclic depsipeptide are therefore of interest. A useful cyclization method for depsipeptides containing a C-terminal α,α-disubstituted α-amino acid, the so-called 'direct amide cyclization' method, has been developed in our laboratory [9][10][11][12][13][14][15][16][17][18][19][20]. The basic concept is shown in Scheme 1: if an amide of type 1 is treated with dry HCl-gas, the corresponding 1,3-oxazol-5(4H)-one derivative 2 is formed via ring closure and elimination of dimethylamine hydrochloride.…”