Effect of the Solvent on the Conformation of a Depsipeptide: NMR‐Derived Solution Structure of Hormaomycin in DMSO from Residual Dipolar Couplings in a Novel DMSO‐Compatible Alignment Medium

Abstract

The macrocyclic compound hormaomycin has been investigated by NMR spectroscopy and by restrained molecular-dynamics simulations. Measurement of residual dipolar couplings induced by dissolving the depsipeptide in a polyacrylamide gel compatible with DMSO and their incorporation into the structure calculation of the title compound improved the precision of the family of structures. In DMSO the macrocyclic ring shows two beta-turns, whose positions in the sequence differ from those found in the CDCl3 solution structure and in the crystal structure obtained from hexylene glycol/H2O (50:50). The bulky side chain consisting of a 3-(2-nitrocyclopropyl)alanine and a chlorinated N-hydroxypyrrole moiety is flexible in DMSO.

Use of RDCs in rigid organic compounds and some practical considerations concerning alignment media

“…Although many exciting publications dealing with conformation determination of peptides (62,63) and oligosaccharides (64-67) appeared, so far no approach in which a simultaneous determination of configuration and conformation was performed has been published for (nonrigid) organic compounds. To develop methodologies that also allow the treatment of flexible compounds is (in our opinion) the next necessary step and will certainly be the breakthrough of RDCs as additional tools in structure determination of organic compounds.…”

Use of a Halogenase of Hormaomycin Biosynthesis for Formation of New Clorobiocin Analogues with 5‐Chloropyrrole Moieties

“…[13] Hormaomycin is a depsipeptide antibiotic formed by Streptomyces griseoflavus W-384. [14][15][16] It also contains a pyrrole-2-carboxylic acid moiety, which is in this case attached by an amide bond to the peptide backbone of the molecule. However, in contrast to clorobiocin and coumermycin A 1 , the pyrrole The depsipeptide antibiotic hormaomycin, which is produced by Streptomyces griseoflavus W-384, contains a 5-chloropyrrole moiety.…”

Residual Dipolar Coupling Enhanced NMR Spectroscopy and Chiroptics: A Powerful Combination for the Complete Elucidation of Symmetrical Small Molecules

“…[7] On the other hand, determination of absolute configuration by time-dependent (TD)-DFT prediction of chiroptical properties (i.e., electronic circular dichroism (ECD) and optical rotatory dispersion (ORD)) has been particularly successful, as long as the relative configuration, and the conformational distribution in the case of flexible compounds, have been previously established (e.g., by NMR spectroscopy). [8,9] Many homodimeric bilaterally symmetric structures can be found in the bispyrrolidinoindoline diketopiperazine family of alkaloids (Scheme 1).…”