3069-52-1Relevant articles and documents
α-Aminoxy Oligopeptides: Synthesis, Secondary Structure, and Cytotoxicity of a New Class of Anticancer Foldamers
Diedrich, Daniela,Moita, Ana J. Rodrigues,Rüther, Anja,Frieg, Benedikt,Reiss, Guido J.,Hoeppner, Astrid,Kurz, Thomas,Gohlke, Holger,Lüdeke, Steffen,Kassack, Matthias U.,Hansen, Finn K.
, p. 17600 - 17611 (2016/11/28)
α-Aminoxy peptides are peptidomimetic foldamers with high proteolytic and conformational stability. To gain an improved synthetic access to α-aminoxy oligopeptides we used a straightforward combination of solution- and solid-phase-supported methods and obtained oligomers that showed a remarkable anticancer activity against a panel of cancer cell lines. We solved the first X-ray crystal structure of an α-aminoxy peptide with multiple turns around the helical axis. The crystal structure revealed a right-handed 28-helical conformation with precisely two residues per turn and a helical pitch of 5.8 ?. By 2D ROESY experiments, molecular dynamics simulations, and CD spectroscopy we were able to identify the 28-helix as the predominant conformation in organic solvents. In aqueous solution, the α-aminoxy peptides exist in the 28-helical conformation at acidic pH, but exhibit remarkable changes in the secondary structure with increasing pH. The most cytotoxic α-aminoxy peptides have an increased propensity to take up a 28-helical conformation in the presence of a model membrane. This indicates a correlation between the 28-helical conformation and the membranolytic activity observed in mode of action studies, thereby providing novel insights in the folding properties and the biological activity of α-aminoxy peptides.
Total synthesis, stereochemical assignment, and antimalarial activity of gallinamide A
Conroy, Trent,Guo, Jin T.,Linington, Roger G.,Hunt, Nicholas H.,Payne, Richard J.
supporting information; experimental part, p. 13544 - 13552 (2012/01/13)
The total synthesis and stereochemical assignment of gallinamideA, an antimalarial depsipeptide of cyanobacterial origin, is described. Synthesis of the four possible N-terminal diastereoisomers of gallinamideA (including the natural product symplostatin4) was achieved using a divergent strategy from a common imide fragment. The natural product and corresponding diastereoisomers were synthesized in 30-33% overall yield in a longest linear sequence of 8 steps. Comparative NMR spectroscopic studies of the four synthetic diastereoisomers with the isolated natural product demonstrated that gallinamideA possesses a dimethylated L-isoleucyl residue at the N-terminus. As such, we have shown that gallinamideA is structurally and stereochemically identical to symplostatin4. GallinamideA and its N-terminal diastereoisomers were also shown to possess significant antimalarial activity with IC 50 values in the nanomolar range against the 3D7 strain of Plasmodium falciparum. Naturally active: The total synthesis of gallinamideA, a cyanobacterium-derived depsipeptide, is described. Four N-terminal diastereoisomers of gallinamide A were prepared by using two key fragments (see scheme). Spectroscopic comparison to the isolated natural product enabled the absolute configuration of the N,N-dimethylated isoleucyl residue to be determined as 25S, 26S. GallinamideA (and its diastereoisomers) were also shown to possess potent antimalarial activity. Copyright
Zinc-catalyzed enantiospecific sp3-sp3 cross-coupling of α-hydroxy ester triflates with grignard reagents
Studte, Christopher,Breit, Bernhard
supporting information; experimental part, p. 5451 - 5455 (2009/03/12)
(Chemical Equation Presented) Zinc chloride does the trick and efficiently catalyzes the enantiospecific cross-coupling of α-hydroxy ester triflates with Grignard reagents under mild conditions. Enantiopure α-hydroxy esters are directly available from the chiral pool or by diazotization of α-amino acids. Substantial variations in both reacting partners are tolerated making this methodology an attractive alternative to enolate alkylation featuring a reversal of polarity.
