Stereochemistry of Protected Ornithine Side Chains of Gramicidin S Derivatives: X-ray Crystal Structure of the Bis-Boc-tetra-N-methyl Derivative of Gramicidin S.

An X-ray crystallographic analysis of the bis-N[SUPδ]-Boc-tetra-N[SUPα]-methyl derivative of gramicidin S, cyclo(-VaI-MeOrn(Boc)-Leu-D-MePhe-Pro-)[SUB2], was undertaken successfully (R-factor = 0.088). As expected, the main chain adopts an antiparallel pleated β-sheet conformation, but the pleated sheet is slightly twisted, and the sense of twisting is opposite to that found in the reported crystal structures of the gramicidin S-urea complex and the bis-N[SUPδ]-(trichloroacetyl) and bis-Nδ-(m-bromobenzoyl) derivatives of gramicidin S. In agreement with the observed resistance toward N-methylation, the urethane NH groups of the protected Orn side chains are hydrogen bonded to the carbonyl groups of the D-Phe residues. However, the side-chain-main-chain hydrogen bonding is in the i → i - 3 mode, although hydrogen bonding in the i → i + 2 mode was deduced from a [SUP1]H NMR study of protected gramicidin S derivatives and was actually found in the crystal structures of the diacylated gramicidin S. [ABSTRACT FROM AUTHOR]