Indole NH Group Research Articles

Structure of a key intermediate in the synthesis of (–)-5-carboxytetrahydroalstonine and (–)-tetrahydroalstonine

Methyl [4aS*-(4 alpha,4a beta,7 beta,13b beta,14a beta)]-7,8,13,13b,14,14a- hexahydro-4-methyl-5-oxo-4H-indolo-[2,3-a]pyrano[3,4-g]qu inolizine-7-carboxylate acetone solvate, C22H22N2O4.C3H6O, Mr = 424.50, triclinic, P1, a = 9.9955(13), b = 10.8523(14), c = 11.9352(14) A, alpha = 63.189(9), beta = 72.286(9), gamma = 72.901(10) degrees, V = 1081.8(2) A3, Z = 2, Dx = 1.30 g cm-3(198K), mu = 0.8554 cm-1, Mo K alpha radiation, lambda = 0.7107 A, F(000) = 452, T = 198 K, R = 0.0435 for 3842 reflections, FO greater than or equal to 4 sigma (FO). The acetone solvent is hydrogen bonded to the indole NH group with relevant parameters: N13...O1A 2.982(2), H13...O1A 2.10(2) A, N--H...O 164(2) degrees. The conformation at the C and D ring junction is quasi-cis [relevant torsion angles are C7--N6--C13B--C13A 9.4(2) degrees and C5--N6--C13B--C14 46.7(2) degrees] while the conformation at the D and E ring junction is cis [relevant torsion angles are 37.8(2) degrees for C5--C4A--C14A--C14 and 41.3(2) degrees for C4--C4A--C14A--C1].

The structure of (±)-21-oxoisopteropodine

Methyl (1'S*,3S*,4a'S*,5a'S*,10a'R*)- 3',4a',5a',6',7',8',10',10a'-octahydro-2-hydroxy-1'-methyl-10'- oxospiro[3H-indole-3,6'-[1'H]pyrano[3,4-f]indolizine-4'-carb oxylate, (1), C21H22N2O5, Mr = 382.42, monoclinic, P21/c, a = 12.920 (4), b = 10.342 c = 15.192 (8) A, beta = 105.68 (3) degrees, V = 1954.4 (14) A3, Z = 4, D chi = 1.30 g cm-3 (298 K), mu = 0.8738 cm-1, Mo K alpha radiation, lambda = 0.7107 A, F(000) = 808, T = 298 K, R = 0.0800 for 1000 reflections, F zero greater than or equal to 4 sigma(F zero). The indole NH group is hydrogen bonded to the amide oxygen, O15' (related by chi, 0.5 -y, -0.5 + z), of the indolizine moiety with relevant parameters: N...O 2.79 (2)A, H...O 2.02 (15) A, N-H...O 145 (14) degrees. A close, non-bonded contact of 2.28 (8) A is also observed between O15' and H7'A (related by -chi, 0.5 + y, 1.5 - z).

Synthesis of arcyriarubin b and related bisindolylmaleimides

The reaction of indolyl magnesium bromide with 2,3-dibromo- N-methylmaleimide (3) in toluene leads to bisindolylmaleimides 6. In THF a monosubstitution product 5 is obtained which after protection of the indole NH-group with the Boc residue can be used to prepare unsymmetrically substituted bisindolylmaleimides, arcyriarubin B given as an example.

Phase separation and hexagonal H II phase formation by gramicidins A, B and C in dioleoylphosphatidylcholine model membranes. A study on the role of the tryptophan residues

The role of the tryptophan-residues in gramicidin-induced H II phase formation was investigated in dioleoylphosphatidylcholine (DOPC) model membranes. 31P-NMR and small angle X-ray diffraction measurements showed, that gramicidin A and C (in which tryptophan-11 is replaced by tyrosine) induce a similar extent of H II phase formation, whereas for gramicidin B and synthetic analogs in which one tryptophan, either at position 9 or 11 is replaced by phenylalanine, a dramatic decrease of the H II phase inducing activity can be observed. Modification of all four tryptophans by means of formylation of the indole NH group leads to a complete block of H II phase formation. Sucrose density centrifugation experiments on the various peptide/lipid samples showed a quantitative incorporation of the peptide into the lipid. For all samples in a 1 10 molar ratio of peptide to lipid distinct bands were found, indicative of a phase separation. For the gramicidin A′/DOPC mixture these bands were analyzed and the macroscopic organization was determined by 31P-NMR and small-angle X-ray diffraction. The results demonstrate that a quantitative phase separation had occurred between a lamellar phase with a gramicidin/lipid ratio of 1 15 and a hexagonal H II phase, which is highly enriched in gramicidin. A study on the hydration properties of tryptophan- N-formylated gramicidin in mixtures with DOPC showed that this analog has a similar dehydrating effect on the lipid headgroup as the unmodified gramicidin. In addition both the hydration study and sucrose density centrifugation experiments showed that, like gramicidin also its analogs have a tendency to aggregate, but with differences in aggregation behaviour which seemed related to their H II phase inducing activity. It is proposed (i) that the main driving force for H II phase formation is the tendency of gramicidin molecules to self-associate and organize into tubular structures such as found in the H II phase and (ii) that whether gramicidin (analogs) form these or other types of aggregates depends on their tertiary structure, which is determined by intra- as well as intermolecular aromatic-aromatic stacking interactions.

Structure-activity studies with somatostatin: The role of tryptophan in position 8

The gastric acid and pepsin inhibitory activities of 21 analogues of somatostatin, the majority modified at position 8, were determined in conscious cats in order to examine the importance of Trp 8 for the activity of somatostatin. Pepsin secretion stimulated by pentagastrin was 5 times more sensitive, compared with the acid secretion, to inhibition by somatostatin. All the analogues showed similar differential sensitivity, indicating a similar specificity of somatostatin receptors involved in the inhibition of these two secretions. Halogenated-Trp 8 analogues of somatostatin were only equipotent or slightly more active than somatostatin against gastric secretion in the cat, whilst these analogues are up to 30 times more potent against growth hormone release in the rat, indicating a different specificity of the two groups of receptors. Studies with the position 8 modified analogues suggest that the electron density of the aromatic nucleus of Trp 8 may be relatively unimportant in determining gastric inhibitory activity, whilst it can be concluded that the role of Trp 8 in somatostatin depends to a large extent on the indole NH group. The precise role of Trp 8 in somatostatin could be an involvement in the binding of somatostatin to its receptors, or involvement in forming the biologically active conformation of somatostatin.

Electronic spectroscopy and deuteration kinetics of tyrosine and tryptophan residues: an application to the study of erabutoxin b.

The fluorescence increase on the deuterium oxide addition to the solvent medium was studied in various tryptophan- (or indole-) and/or tyrosine-containing model compounds. It was shown how the rates of the deuteration at the indole NH group of tryptophan and at the OH group of tyrosine could be followed independently of each other. The method was applied to a study of erabutoxin b molecule, a neurotoxic protein from a sea snake, to analyze the microenvironments of its single tryptophan and tyrosine residues. It was shown that the "functionally invariant" single tryptophan residue was exposed to the solvent in the surface of the molecule and that the "structurally conserved" single tyrosine residue was buried in the molecule. The rate of deuteration of the tyrosine residue (80 s(-1) at pH 6.3 and 33 degrees C) was 1/20 of that of an exposed tyrosine. It was also found that the amino group of Lys-27 quenched the fluorescence of Trp-29 but its deuteration had no effect on the fluorescence.

Metabolism of lergotrile to 13-hydroxy lergotrile, a potent inhibitor of prolactin release in vitro

This chapter discusses the perspectives in the design and application of dopamine receptor agonists. The chapter discusses main pharmacological and clinical achievements as well as the essential results of the search of pharmacophores and of tentative receptor models, to provide the basis for understanding “third generation” of dopamine receptor agonists. The era of dopamine receptor pharmacology began around 1960. Heralded by the discovery of the neurotransmitter role of dopamine, it was previously regarded only as a metabolic precursor of noradrenaline. A new avenue of investigation of the interactions of agonistic and antagonistic ligands with receptor models directly derived from the structure of the protein is opened by recent advancements. Thus, progress in indirect modeling, based on steric and electronic properties of the ligands, plays an important role not only in the design of new active compounds, but also in the improvement and the validation of the direct models. In these models, it has been generally accepted that at least one phenolic or equivalent function, such as the indole NH group of the ergolines, acts as a hydrogen bond donor with respect to a site of the receptor. The recent discovery of potent dopamine agonists devoid of such functions suggests that recognition modes other than hydrogen bonding may be involved in the corresponding region of the receptor.

Mechanism of graft copolymerization of vinyl monomers with silk fibroin

In order to examine the mechanism of graft copolymerization to silk fibroin, polymethylmethacrylate (PMMA) was synthesized using model systems of amino acid-ferrous iron-hydrogen peroxide. It was shown that the phenol OH group of tyrosine and the indole NH group of tryptophan are the most active in chain transfer. The presence of amino acid residues in graft PMMA was established by IR spectroscopy.

The Glc Separation of Indole Amines and Indole Alcohols as Heptafluorobutyryl Derivatives

Abstract Indole amines and indole alcohols were converted to heptafluoro-butyryl (HFB) derivatives by an acyl transfer reaction with heptafluoro-butyrylimidazole. The indole NH group as well as all amino and hydroxyl groups were acylated. The HFB derivatives have excellent gas chroma-tographic properties and can be used with either hydrogen flame or electron capture detection systems. Mass spectra of the HFB derivatives of biologic N, N-dialkyl indole amines are very characteristic; these compounds can be identified easily by GLC-MS methods.