NMR spectra and conformational analysis of some 4,5-dihydro-s-triazolo[3,4-d][1,5]benzothiazepine derivatives

High field ¹H and ¹³C nmr spectra of a series of 1-substituted-4,5-dihydro-s-triazolo[3,4-d][1,5]benzothiazepine derivatives have been recorded. These have shown that, unless X = H or O, the molecules occur as a mixture of two slowly interconverting conformers at ambient temperatures. Variable temperature nmr experiments disclosed that the energy barrier to interconversion varies with the size of the substituent X located at position 1 of the fused s-triazole ring.     

Anticancer effect of three pyrazole derivatives

The evaluation of the cytotoxic properties in vitro of three synthetic tripods containing pyrazole: N,N-bis[(3,5-dimethylpyrazol-1-yl)methyl]aniline (1); N,N-tetrakis[(3,5-dimethylpyrazol-1-yl)methyl]-para-phenylenediamine (2); and N,N-tetrakis-[(1,5-dimethylpyrazol-3-yl)methyl]-para-phenylenediamine (3), was examined for their cytotoxic activity on two tumor cell lines: P815 (murin mastocytoma) and Hep (human laryngeal carcinome). While the compound 2 shows a small cytotoxic activity, compounds 1 and 3 are more cytotoxic against both cell lines. However, this cytotoxicity is more pronounced against Hep cell line (IC50: 3.25 microg mL(-1) for compound 1 and 6.92 microg mL(-1) for compound 3) than P815 cell line (IC50: 17.82 microg mL(-1) for compound 1 and 37.21 microg mL(-1) for compound 3). Statistical analysis shows that the compound 1 is two- to threefold more cytotoxic than compound 3 (P < 0.05). Interestingly, the cytotoxicity induced by compound 1 against Hep cell line is more important than that induced by adriamycin used as a positive control.     

Optical rotary dispersion of nitrobenzene derivatives—IV : Absolute conformation of twisted nitrobenzen derivatives and its control through conformational transmission

The origin of Cotton effect shown by o-nitrobenzoyl esters is discussed. The Cotton effect observed for 1-(?)-methyl ester of 3-nitrophalic acid and 4-nitrohemimellitic acid (6 and 12), indicated that the favoured twisting direction of the nitrobenzene moiety is determined by the asymmetric menthyl group through the intervening carboxyl groups. This provides a new concept in conformational analysis of aromatic compounds. Extending the concept of conformational transmission to 2,2′-dinitrobipenhyl derivatives with known ab twisted nitrobenzene was related to the sign of the Cotton effect at 330 nm in accordance with the result of X-ray crystal analysis 1-(?)-menthyl 4-bromo-2-nitrobenzoate (1)     

Stereoselective synthesis and conformational analysis of pseudo-heptapeptides: Part 5

The stereoselective synthesis of pseudo-heptapeptides 8, 9 and 12, incorporating a 2,6-diamino-4-methylen-1,7-heptanedioic acid residue, was accomplished starting from chiral synthon 3, a masked unnatural dipeptide derived from an l-valine unit and (2R)-methylaspartic acid. Investigations of the conformational preference and structure of these unnatural peptides were carried out using ¹H NMR and IR spectroscopic data and a conformational analysis based on molecular dynamics (MD).     

Conformational analysis of 3,4-dihydropyridine and its alkyl derivatives

The geometry of dihydropyridine and its alkyl derivatives was studied by the molecular mechanics method. The dihydrocycle was found to be mobile; however, substituents exert little effect on its distorted sofa conformation. The alkyl groups attached to the saturated carbon atoms occupy pseudo-equatorial position in monosubstituted and pseudo-axial positions in disubstituted 3,4-dihydropyridines. Unusually high barriers to inversion of the dihydrocycle were observed incis-3,4-dialkyl-3,4-dihydropyridines caused by the eclipse of the substituents in the transition state.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1009–1012, June, 1994.     

5-Arylideneaminouracyls: IV. Phosphorylated derivatives and their biological activity

It extension of the studies on the search for the new biologically active 5-aminouracyl derivatives, we synthesized by the reaction of dialkylphosphites with arylideneuracils respective aminomethylphosphonates. The high level of the antiviral and anti-mycobacterial activity of the target compounds correlates well with the physicochemical parameters characterizing their structure.     

The santonins : Qantitative conformational analysis

Empirical valence force-field calculations have been used to investigate the conformations and relative strain energies of α-santonin, β-santonin, and their C(6) epimers. The cis-fused γ-lactone ring is energetically preferred over the trans and the nearly eclipsed C(13)-C(11)-C(12) = 0 torsion angle plays a key role in stabilising the isomers with a pseudo-equatorial Me group at C(11).     

Vinyl derivatives of 2, 5-diaryl-1, 3,4-oxadiazoles

Vinyl derivatives of 2, 5-diaryl-1, 3, 4-oxadiazoles have been synthesized and some of their physical properties have been studied.     

Synthesis and conformational analysis of some cyanomethylene derivatives of piperidines

Five 4-dicyanomethylene derivatives 6–10, N-cyanoacetyl-cis-2,6-diphenylpiperidin-4-one 11 and 4-cyano(ethoxycarbonyl)-methylene-cis-2,6-bis(o-chlorophenyl)piperidine 12 were synthesised by condensing the appropriate piperidin-4-ones 13–17 with malononitrile/ethylcyanoacetate and their ¹H and ¹³C NMR spectra were recorded. The ¹H-¹H COSY spectrum for 6 and NOESY spectra for 8, 10, and 11 were also recorded. Based on coupling constants and the results obtained from NOESY spectra boat conformation for 10 and epimerised chair conformations for 8 and 9 have been proposed. Other derivatives adopt normal chair conformations. Theoretical calculations and the ¹H and ¹³C chemical shifts also support the above conformations. Mass spectra were also recorded for 6–12.     

Vinyl derivatives of 2, 5-diaryl-1, 3,4-oxadiazoles

Vinyl derivatives of 2, 5-diaryl-1, 3, 4-oxadiazoles have been synthesized and some of their physical properties have been studied.     

Vibrational and conformational analysis of chloromethylacetate and some deuterated derivatives

The i.r. spectra of gaseous, amorphous and crystalline solid and the Raman spectra of liquid and amorphous solid chloromethylacetate, CH₃COOCH₂Cl, and three deuterated derivatives, CH₃COOCD₂Cl, CD₃COOCH₂Cl and CD₃COOCD₂Cl, were obtained and an assignment proposed. Only one conformer of CMA was found to be present in all phases. Band contour simulation of the i.r. vapour phase bands showed this to be the s-cis gauche conformer. This was confirmed by a study of the partially deuterated compound CD₃COOCDHCl, of which the separate transitions originating from the antiperiplanar and synclinal isolated CH stretches were observed in the i.r. spectra of the vapour and crystalline solid and in the Raman spectrum of the vapour.     

Synthesis and conformational analysis of 9,10-bis-aminomethyl-11,12-dicarboxy-dibenzobarrelene derivatives

The synthesis of bis-γ-amino acid dibenzobarrelene derivatives (9,10-bis-aminomethyl-11,12-bis-carboxy-dibenzobarrelene) is presented. Bromomethylation of anthracene followed by azide substitution gave 9,10-bis-azidomethylanthracene. Azide reduction, N-Boc protection, and Diels-Alder cycloaddition in DMAD furnished the protected 9,10-bi-aminomethyl-11,12-dicarboxy-dibenzobarrelene derivative, which was further converted into the bis-γ-amino acid methyl ester, the N-Boc-protected bis-γ-amino methyl amide, and a bis-γ-lactam. Monte Carlo simulations and X-ray analysis of the 9,10-substituted dibenzobarrelenes revealed an exposed hydrophobic surface surrounded by amino and carboxy groups.     

Thermal studies on metal complexes of 5-nitrosopyrimidine derivatives IV

The thermal decomposition processes of the complexes of 6-amino-5-nitrosouracil with Fe(II), Co(II), Ni(II) and Cu(II) have been studied using TG and DSC techniques. Dehydration energies have been calculated from the DSC curves.     

NMR study of 5-substituted pyrazolo[3,4-c]pyridine derivatives

Substituted pyrazolopyridines are potent inhibitors of phosphodiesterases and cyclin-dependent kinases. In this study, NMR was used to investigate the potential N1-H and N2-H tautomerism of 5-substituted pyrazolo[3,4-c]pyridine derivatives. Six compounds were fully characterized by using (1)H, (13)C, and (15)N chemical shifts and indirect (1)H--(13)C and (1)H--(15)N coupling constants. The (1)H NMR spectra were measured over a broad range of temperatures. All of the compounds were shown to exist predominantly in the N1-H tautomeric form. Complementary quantum-chemical calculations of the chemical shieldings and indirect spin-spin couplings support the structural conclusions drawn.     

The analysis of mixtures: IV

The analysis of mixtures has been re-examined and extended. The results have been applied to several mixtures, including steroids, distilled from a direct insertion probe with promising results. An experimental scheme is described to enable the determination of the number of components in a mixture by two distinct methods. This work forms an early stage in a general mixtures analysis system.     

Theoretical conformational analysis of cyclopendant phosphorus-organic complexes,derivatives of triazacyclononane

The method of molecular mechanics has been used to calculate the strain energy of complex formation of two new phosphorus-organic cyclopendant ligands, derivatives of 1,4,7-triazacyclononane. It is shown that lengthening the pendant groups by one CH₂ unit increases the volume of the ligand cavity in hexadentate coordination. However, this requires a large strain energy, which leads to a loss of stability of the complexes with metal cations. A decrease in the strain energy for penta- and tetradentate ligand profiles accounts for the appearance of selectivity towards cations with small radii. Modifying the structure of cyclopendants based on triazacyclononane by means of benzene rings does not produce a ligand profile with a definite structure, or selective binding of metal cations.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1075–1079, May, 1990.     

Solvent effect on the conformational behaviour of amino acid and oligopeptide derivatives

The solvent effect on acetyl amino acid methyl esters and C- and N-protected di- and tripeptide derivatives has been studied in deuterium oxide (D₂O), 1.1.1.3.3.3-hexafluoroisopropanol (HFiP), dimethyl sulfoxide (DMSO) and methylene chloride (CH₂Cl₂). The interpretation is based on the amide I region. For the amino acid derivatives the relative shift of the amide I signal clearly indicates the strength of the interaction with the solvent molecules. However, in HFiP and DMSO solutions the occurrence of two overlapping signals for the amide I and the ester carbonyl signal, respectively, indicates the existence of two major conformers. Knowing the solvent effects on the small amino acid esters allows the assignment of the signals in di- and tripeptide derivatives. Although the identification of turn structures in these flexible molecules is not possible, the band positions and intensity of the deconvoluted amide I region clearly shows that certain conformers can be stabilised. It can be concluded that the band profile in the amide I region is determined by the number of amino acid residues linked in the molecule, the bulkiness of the side chains and their sequence and to a major extend by the solvent properties.