1.Synthesis of histidinoalanine: a comparison of β-lactone and sulfamidate electrophiles.
Taylor CM1, De Silva ST. J Org Chem. 2011 Jul 15;76(14):5703-8. doi: 10.1021/jo200744d. Epub 2011 Jun 14.
Previous syntheses of histidinoalanine (HAL) have led to mixtures of regioisomers and/or stereoisomers. For example, opening of N-Cbz-D-serine-β-lactone (6) with Boc-L-His-OMe (5) gave a 2:1 mixture of τ- and π-regioisomers. The sulfamidate 10, derived from N-benzyl-D-serine methyl ester (11), was reacted with Boc-L-His-OMe (5) to give the τ-HAL derivative 17 as a single isomer in 57% yield. A similarly prepared τ-HAL 19, bearing protecting groups that were all hydrogenolytically labile, led to the free bis-amino acid, τ-L-histidinyl-D-alanine (τ-4), as a salt-free standard for amino acid analysis.
2.Preparation of optically pure δ-lactones using diastereomeric resolution with amino acid as resolving agent.
Shimotori Y1, Hoshi M, Seki S, Osanai T, Okabe H, Ikeda Y, Miyakoshi T. J Oleo Sci. 2015;64(1):75-90. doi: 10.5650/jos.ess14124.
Synthesis of optically pure δ-lactones by diastereomeric resolution was investigated. Amino acid derivatives, which can be obtained at a relatively low cost, were used as resolving agents. Six optically pure δ-lactones were efficiently synthesized using Cbz-L-alanine without other expensive resolving agents. Both enantiomers of δ-lactone obtained had over 98% enantiomeric excesses. This diastereomeric resolution is very efficient for the preparation of optically pure δ-lactones.
3.Conformational ensembles of flexible beta-turn mimetics in DMSO-d6.
Koivisto JJ1, Kumpulainen ET, Koskinen AM. Org Biomol Chem. 2010 May 7;8(9):2103-16. doi: 10.1039/b921794k. Epub 2010 Mar 11.
Beta-turns play an important role in peptide and protein chemistry, biophysics, and bioinformatics. The aim of this research was to study short linear peptides that have a high propensity to form beta-turn structures in solution. In particular, we examined conformational ensembles of beta-turn forming peptides with a general sequence CBz-L-Ala-L-Xaa-Gly-L-Ala-OtBu. These tetrapeptides, APGA, A(4R)MePGA, and A(4S)MePGA, incorporate proline, (4R)-methylproline, and (4S)-methylproline, respectively, at the Xaa position. To determine the influence of the 4-methyl substituted prolines on the beta-turn populations, the NAMFIS (NMR analysis of molecular flexibility in solution) deconvolution analysis for these three peptides were performed in DMSO-d(6) solution. The NBO (natural bond orbital) method was employed to gain further insight into the results obtained from the NAMFIS analysis. The emphasis in the NBO analysis was to characterize remote intramolecular interactions that could influence the backbone-backbone interactions contributing to beta-turn stability.
4.Design and synthesis of a tetradentate '3-amine-1-carboxylate' ligand to mimic the metal binding environment at the non-heme iron(II) oxidase active site.
Dungan VJ1, Ortin Y, Mueller-Bunz H, Rutledge PJ. Org Biomol Chem. 2010 Apr 7;8(7):1666-73. doi: 10.1039/b921934j. Epub 2010 Feb 4.
Non-heme iron(II) oxidases (NHIOs) catalyse a diverse array of oxidative chemistry in Nature. As part of ongoing efforts to realize biomimetic, iron-mediated C-H activation, we report the synthesis of a new 'three-amine-one-carboxylate' ligand designed to complex with iron(II) and mimic the NHIO active site. The tetradentate ligand has been prepared as a single enantiomer in nine synthetic steps from N-Cbz-L-alanine, pyridine-2,6-dimethanol and diphenylamine, using Seebach oxazolidinone chemistry to control the stereochemistry. X-Ray crystal structures are reported for two important intermediates, along with variable temperature NMR experiments to probe the hindered interconversion of conformational isomers of several key intermediates, 2,6-disubstituted pyridine derivatives. The target ligand and an N-Cbz-protected precursor were each then complexed with iron(II) and tested for their ability to promote alkene dihydroxylation, using hydrogen peroxide as the oxidant.