Preparation and properties of some α-aza-amino-acid derivatives,their possible use in peptide synthesis

Some derivatives of azaglycine and azaphenylalanine are described. Esters of acetyl- and benzoyl-aza-amino-acids rapidly cyclise to stable oxadiazolones and it is concluded that similar derivatives would be unsuitable for aza-peptide synthesis. t-Butyloxycarbonyl-azaglycine azide was too unreactive for use in peptide synthesis. Benzoyl-azaglycylphenylalanine ethyl ester and acetyl-azaphenylalanylphenylalanine ethyl ester were prepared by coupling benzoyl hydrazide and N-acetyl-N'-benzylhydrazide respectively with 2,4-dinitrophenyloxycarbonyl-phenylalanine ethyl ester.     

Synthesis of O-acylbenzohydroxamic acids and their use in peptide synthesis

The addition of N-protected amino acids to benzonitrile oxides yields activated esters, which on coupling with amino acid esters lead to peptides.     

Stannyl derivatives of naphthalene diimides and their use in oligomer synthesis

2-Stannyl and 2,6-distannyl naphthalene diimides (NDIs) can be synthesized through the palladium-catalyzed reaction of the appropriate bromo derivatives with hexabutylditin. The utility of these precursors in palladium catalyzed cross-coupling reactions is demonstrated by the synthesis of bi- and ter-NDI derivatives, UV-vis, cyclic voltammetry, and n-channel organic field-effect transistor data for which are compared to those of the monomeric parent NDI.     

Total synthesis of mannosyl tryptophan and its derivatives

Glycosylation is one of the most important post- or co-translational modifications of proteins, which affects the biological activities of the parent proteins by influencing the higher-order structure. Recently, a highly novel variant of glycoproteins that incorporate a C-glycosylated amino acid was identified in various proteins. The total synthesis of one such C-glycosyl amino acid, namely, C (2)-alpha-D-C-mannosylpyranosyl-L-tryptophan and related peptides were successfully achieved. The mannose and tryptophan moieties were connected via ring opening of benzyl-protected 1,2-anhydro-mannose by a lithiated indole derivative. After the functional group conversion and deprotection steps, the glyco-amino acid was synthesized in a concise and stereoselective manner, in high overall yields. The stereoisomer, C (2)-alpha-D-C-glycosylpyranosyl-L-tryptophan was synthesized in a similar way. Furthermore, it was revealed that the intermediate azido acid can serve as a useful building block for peptide elongation. A synthetic route for the peptide bond formation of a glycopeptide, without protection of the hydroxyl groups, using the triazine salt derivative as a coupling reagent is also reported.     

Convenient synthesis of chiral tryptophan derivatives using Negishi cross-coupling

A facile synthetic procedure for chiral tryptophan derivatives using Negishi cross-coupling reaction of serine-derived iodoalanine with 3-haloindole is described. The best result was obtained when the reaction of N-tosyl-3-bromoindole with N-Cbz-iodoalanine methyl ester was carried out by the combination of Pd₂(dba)₃ and sterically hindered ferrocenyl ligand Q-PHOS. This reaction condition not only gave the desired tryptophan derivative as high as 76% yield, but also suppressed the formation of undesired products, the dehalogenated indole and the homodimer of indole, which were difficult to separate. This reaction was extended to the synthesis of various tryptophan derivatives having substituents on the benzene ring. The characteristic of this reaction is the practical biomimetic synthesis of chiral tryptophan derivatives in one-step.     

The facile synthesis of a series of tryptophan derivatives

This study reports a facile method for the synthesis of a variety of 5- and 6-substituted tryptophan derivatives that are difficult to prepare using alternative enzymatic approaches. Acylation of an activated amino acid, derived from serine in situ, is coupled with an enzymatic resolution step to furnish enantiopure analogues bearing a range of electron withdrawing and releasing substituents. Isolation of a dehydroalanine derivative as a by-product from some reactions provides some insights into the likely mechanism of the reaction.     

Factors affecting the ultramicro-determination of tryptophan,kynurenine and their derivatives

The factors affecting the ultramicrodetermination of tryptophan and kynurenine were investigated by paper electrophoresis, paper chromatography and spectrophotometry. The electrolyte used in electrophoresis influences the mobility, the separation and the ultraviolet spectra of tryptophan and kynurenine. The pre-treatment of filter paper for chromatography did not influence the R_F of tryptophan and kynurenine, but interfered with their quantitative determination. The effect of ultraviolet irradiation of d-, l-, and dl-tryptophan as well as d-, l-, and dl-kynurenine was studied.     

Tricarbonylchromium(0) promoted stereoselective transformations of ephedrine and pseudoephedrine derivatives

(−)-(1S,2S)-(N,O-Dimethylephedrine)tricarbonyl chromium(0) (6) and (−)-(1S,2R)-(N,O-dimethylpseudoephedrine)tricarbonylchiromium(0) (22) undergo completely stereoselective ortho deprotonation upon treatment with alkyllithium base, followed by addition of an electrophile. In both cases, exclusive removal of the pro-(R)-ortho proton was confirmed by single crystal X-ray structure analyses of the methylated products. Addition of methyllithium onto the ortho-formylated derivative of complex (6) occurs stereoselectively, the stereochemistry of the major product being confirmed by a single crystal X-ray structure determination. The results presented demonstrate an efficient transfer of chirality from a side chain onto the (arene)tricarbonylchromium(0) complex and back to a different side chain.     

HPLC enantioseparation of amino acids and their protected derivatives used in peptide synthesis with pre-column chiral derivatization

Summary Indirect chiral separation methods based on enantiomeric derivatizations were developed in order to monitor optical purity of uncoded amino acids and a new series of amino acid derivatives. Marfey's reagent was used for derivatization of amino groups: whilst boxyl groups were derivatised with (1R, 2R)-or (1S, 2S)-2-amino-1(4-nitrophenyl)-1,3-propanediol reagents were used, respectively. The separations of diastereomeric derivatives formed via derivatization were optimized in RP-HPLC and NP-HPLC systems. Presented at Balaton Symposium on High Performance Separation Methods, Siófok, Hungary, September 1–3, 1999     

Unsaturated 1,5-diketones and their halogen-substituted derivatives — Preparation and use in the synthesis of heterocycles

Published data and the results of the authors' own research on methods for the production of unsaturated 1,5-diketones and halogen-substituted 2-pentene-1,5-diones and their use in the synthesis of difficulty obtainable pyrylium, 3,5-dichloropyrylium, and 3-chlorothiopyrylium salts, aroylfurans, 40-chloroaroylfurans, isoxazolines, pyrazolines, 3,5-dichloropyridines, 1,4-tetramethylenebispyridines, and others are summarized. Aspects of the structure of 2-pentene-1,5-diones and their 2,4-dichloro-substituted analogs and features of their heterocyclization are discussed in comparison with pentane-1,5-diones and their 2,4-dichloro-substituted derivatives.N. G. Chernyshevskii Saratov State University, Saratov, K. A. Fedin Saratov State Pedagogical Institute, Saratov. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1299–1319, October, 1996. Original article submmited June 8, 1995     

Hydroxamic acids and their derivatives—III Preparation of esters of pivalohydroxamic acid and their use in peptide synthesis

Reaction of N-protected amino acids with pivalonitrile oxide affords “active esters” which are useful in peptide syntheses.     

N-hydroxypeptides. I. Preparation of N-benzyloxy-α-amino acid anhydrides and their use in peptide synthesis

N-Benzyloxy-DL-α-amino acids are transformed with phosgen to N-benzyloxy-DL-α-amino acid anhydrides which react smoothly with the amino component of peptides to give the corresponding N-benzyloxypeptides.     

The synthesis of tetrafluoro-sulphobenzoic acids and their derivatives

The tetrafluorosulphobenzoic acids 1,2-HO₂C.C₆F₄.SO₃H (I) and 1,4-HO₂C.C₆F₄.SO₃H (II) have been synthesised [1] by oxidation of respectively 4,5,6,7-tetrafluorobenzo [b] thiophen- 2-carboxylic acid (III) [2] and 4-mercaptotetrafluorobenzoic acid (IV) [3].By-products were obtained when (III) was oxidised with either trifluoroperacetic acid or potassium permanganate.A number of reactions of these intermediates have been investigated and the products characterized, eg reaction of (I) with SoCl₂ gave tetrafluoro-1,2-sulphobenzoic acid cyclic anhyride (V). Although no significant change was observed when (II) was similarly treated reaction of (II) with DMF/SOCl₂ gave 1,4-Cl.C₆F₄.COCl. The diacid fluorides 1,2-FOC.C₆F₄.SO₂F (VI) and 1,4-FOC.C₆F₄.SO₂F (VII) were obtained when (I) and (II) respectively were reacted with sulphur tetrafluoride. The use of excess SF₄ gave 1,2- or 1,4- [F₃C.C₆F₄.SO₂F].     

Functionalised enaminones and their use in heterocyclic synthesis

A series of enaminones derived from 2,4-dioxocyclohexane carboxylic acid esters has been prepared. The use of some of the new derivatives in the synthesis of some quinazolones and imidazoloquinazolines is illustrated.     

Polyfluorovinyl lithium reagents and their use in synthesis

The use of polyfluorovinyl lithium reagents in synthesis since their original discovery almost simultaneously by Seyferth and Tarrant and their development by Normant is reviewed. More recent developments in the field using CFC replacements as starting materials has given a new impetus to the use of these important reagents as building blocks for the development of new materials. These new reactions are also reviewed.