ABSTRACT
3,4,6-Tri-O-acetyl-2-deoxy-2-hydroxyimino-beta and -alpha-D-lyxo-hexopyranosides of thiophenol (3, 4) and the methyl ester of N-benzoyl-L-cysteine have been synthesised by condensation of 3,4,6-tri-O-acetyl-2-deoxy-2-nitroso-alpha-D-galactopyranosyl chloride with thiophenol and the L-cysteine derivative, respectively. The conformation of the sugar residue and configuration of the anomeric centre as well as of the hydroxyimino group were established on the basis of the 1H NMR (DQF-COSY, ROESY, TOCSY) spectrometric techniques and polarimetric data. Additionally, the structure of S-[3,4,6-tri-O-acetyl-2-deoxy-2-(Z)-hydroxyimino-beta-D-lyxo -hexopyranosyl]-thiophenol (3) was supported by X-ray diffraction data.
Subject(s)
Deoxy Sugars/chemical synthesis , Oximes/chemical synthesis , Phenols/chemical synthesis , Sulfhydryl Compounds/chemical synthesis , Thioglycosides/chemical synthesis , Carbohydrate Conformation , Magnetic Resonance Spectroscopy , Models, Chemical , Models, Molecular , Temperature , Thioglycosides/chemistry , X-Ray DiffractionABSTRACT
PNAs are relatively novel DNA analogues, intensively studied due to their potential as gene-targeted drugs with antigene and antisense properties. In 1996 we elaborated a new method of synthesis of PNA monomer backbones based on the Mitsunobu reaction with N-tosyl-protected (Tos) amino acid esters as acidic components of the reaction. Since the method used for the Tos group removal requires conditions incompatible with various functional groups, here we modified the procedure by replacing the tosyl group with o-nitrobenzenesulfonyl (o-NBS) group. Using the new procedure we obtained protected PNA monomer backbones with various amino acid side chains. The pseudodipeptide secondary amine groups were then deprotected by thiolysis, and after standard work-up acylated with thymin-1-ylacetic acid, to give the protected monomers. Since the deprotection of the secondary amine group occurs under mild conditions, the procedure is of general applicability and allows various modifications of PNA structure by using diverse beta-amino alcohols and alpha-amino acid esters.
Subject(s)
Peptide Nucleic Acids/chemical synthesis , Amino Acids , Indicators and Reagents , Tosyl CompoundsABSTRACT
cyclo(D-Phenylalanyl-trans-4-fluoro-D-prolyl), c(D-Phe-D-FPro), was synthesized and its conformation determined both in solution and in the solid state by 1H NMR and X-ray analysis, respectively. In the crystals the 2.5-diketopiperazine (DKP) ring assumes the uncommon conformation, for cyclodipeptides containing Pro residue, of a flattened chair, which seemingly results from a compromise between, on the one hand, the DKP-aromatic intramolecular ring-ring attraction (folding), requiring the C alpha--C beta bond of the Phe to be axial, and, on the other hand, the intrinsic tendency of the Pro residue to have its C alpha--C beta bond equatorial. Unlike the solid state, the 1H NMR data in CDCl3 and C6D6 demonstrate that in both solutions the DKP ring assumes a boat-like shape, typical for the Pro-containing cyclodipeptides, with the equatorial C alpha--C beta bonds in both amino acid residues, which preclude ring-ring folding. A similar conformation was encountered in the closest analog of c(D-Phe-D-FPro), viz, in c(Phe-Pro), both in solution (21, 22, 26) and in the solid state (12). A subtle interplay of intramolecular interactions introduced into a cyclodipeptide by a Pro-type and a Phe-type residue is emphasized.
