Bogdan Liberek

Synthesis of diazoketones derived from α-amino acids; problem of side reactions

Abstract Optimum conditions of synthesis of eight diazoketones derived from optically active N-(t-butyloxycarbonyl)- and N-benzyloxycarbonylamino acids have been described. The problem of formation of by-products during Arndt-Eistert synthesis of β-homoamino acids at the stage of reaction of mixed anhydride with a weak nucleophile-diazomethane - has been discussed.

Synthesis of achiral and chiral peptide nucleic acid (PNA) monomers using Mitsunobu reaction

Abstract Peptide nucleic acids (PNAs) are intensively studied DNA analogues. We elaborated an efficient procedure for the synthesis of N-, C-protected pseudodipeptides with a reduced peptide bond and then peptide nucleic acid (PNA) monomers, based on the Mitsunobu reaction of N-Boc-β-amino alcohols with N-o-nitrobenzenesulfonyl-protected (oNBS-protected) amino acid esters. 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 appropriate work-up, acylated with thymin-1-ylacetic acid to give the protected monomers. The procedure seems to be of general applicability and allows various modifications of PNA structure by using diverse alcohols and amino acid esters.

Tetrazole analogues of amino acids and peptides— V: Syntheses of peptide derivatives containing tetrazole analogues of amino acids in C-terminal position

Abstract The title compounds were prepared by coupling of N-protected amino acids with triethylammonium salts of tetrazole analogues of amino acids followed by removal of amino protection. Alternatively the products were prepared from amides of N-protected peptides by dehydration to the corresponding nitriles, formation of the tetrazole nucleus by the reaction of the cyano group with ammonium azide, and removal of amino protection.

Tetrazole analogues of amino acids and peptides IV : Resolution of racemic tetrazole analogues of N-benzyloxycarbonyl amino acids by means of hydrazide of L-tyrosine☆

Abstract Racemic tetrazole analogues of N-benzyloxycarbonyl derivatives of alanine, S-benzyl-cysteine, leucine, phenylalanine and valine were resolved by means of L -tyrosine hydrazide. The resolution of tetrazole analogue of N-benzyloxycarbonyl- DL -phenylalanine provided the L -enantiomer. From the other fractionation experiments tetrazole analogues of N-benzyloxycarbonyl- D -alanine, -S-benzyl- D -cysteine, - D -leucine, and - D -valine were obtained.

Thin-Layer chromatographic separation of the Z and E rotational isomers of α-N-nitroso-N-alkylamino acids

Abstract Thin-layer chromatography at 0–2 C affords a simple and rapid method for the detection and separation of the Z and E isomers of N-nitroso-N-alkylamino acids. The procedure enables conformational purity of the crystals to be determined and conformational Z⇌E interconversions to be studied.

Conformation of dioxopiperazines: Part 7. The dependence of the internal coordinates on puckering of the 2,5-dioxopiperazine ring

Abstract The variations of the bond lengths, the endo- and the exocyclic valence and torsion angles involved in the 2,5-dioxopiperazine, DOP, ring have been inv

Conformation of cyclodipeptides. factor analysis: a convenient tool for simplifying conformational studies of condensed poly-ring systems: prolyltype cyclopeptides

Abstract AFA analysis (AFA), also known as principal-component analysis, was used in conformational studies of the condensed 2,5-dioxopiperazine/pyrrolydine (DOP/PYR) 6/5-membered two-ring system, a compound typical of cyclodipeptides comprising prolyl-type amino acid residues. The study is based on the analysis of 30 various X-ray conformers of the molecular frame in question. The results were evaluated and discussed using ring-puckering theory (RPT) as a reference. Complete mutual correspondence between the AFA and the RPT results was found, when both rings are considered separately, which is the prerequisite to using RPT. This correspondence allows a clear-cut physical interpretation of the AFA results, which are otherwise abstract in nature. Thus, two or three independent puckering variables were found for the DOP and PYR rings, respectively, and they acquire the physical significance of the absolute amplitudes of the basic pucker modes, typical of the respective rings. The term absolute is used for puckering with respect to the planar conformer of reference. Subsequent AFA treatment of the condensed DOP/PYR system allowed identification of five conformational variables necessary and sufficient to describe the concerted two-ring puckering completely. Each of the respective basic pucker modes defines a unique pattern of conformational variation of the whole two-ring system. In contrast to the separated ring cases, the origin of the five-dimensional conformational space of DOP/PYR is placed at the mean conformer and it spans physically accessible conformational deviations around the mean. When a conformer other than the mean (e.g. planar) one is chosen initially as a reference, AFA automatically brings the system to the basis set of local deviations around the mean. The results obtained demonstrate that AFA may be a very powerful technique in conformational studies based on an evaluation of a large collection of mutually consistent data. Factor analysis is especially useful in analyses of condensed poly-ring systems, not amenable to the RPT treatment.