An efficient, one-pot reductive alkylation of indoles with N-protected aminoethyl acetals in the presence TES/TFA is reported. It represents first general method for direct synthesis tryptamine derivatives from and nitrogen-functionalized acetals. This convergent versatile approach employs safe inexpensive reagents, proceeds under mild conditions, tolerates several functional groups. The new procedure was efficiently applied to a gram-scale both luzindole, reference MT2-selective melatonin...

The selective C3-alkylation of indoles with N-protected ethanolamines involving the "borrowing hydrogen" strategy is described. This method provides convenient and sustainable access to several tryptamine derivatives.

Abstract A copper‐based catalytic technique for the regioselective hydroboration and hydrosilylation of dehydroalanine derivatives has been developed. This method introduces synthetically versatile boron silicon groups, while simultaneously performing a anti‐Markovnikov hydrofunctionalization dehydroalanines dehydropeptides synthesis amino acids peptides bearing unnatural side‐chains. The products obtained were expediently converted into valuable nonproteinogenic acid building blocks...

A facile synthetic approach to the direct preparation of various novel unnatural boronated protected tryptophans using a regio- and chemoselective electrophilic substitution 4- 5-boronated indoles with N-protected dehydroalanine is described. The gram-scale synthesis two free tryptophan boronic acids also reported.

The modular and versatile synthesis of C4-substituted tryptophan derivatives by direct functionalization easily available N-acetyl 4-boronate methyl ester via transition metal-catalyzed metal-mediated cross coupling reactions is described. versatility the chemistry highlighted gram-scale 4-boronated N-acetyl-tryptophan rapid C4-aryl, C4-alkyl, C4-cyano, C4-trifluoromethyl, C4-azido, C4-hydroxy derivatives. utility our methodology illustrated through quick approach to tricyclic azepino indole...

Stimulus-responsive cleavage reactions have found broad use to direct drug release at a particular target disease area. Increased levels of reactive oxygen species (ROS) been associated with the development and progression cancer several other states, motivating conjugates that can undergo chemoselective ROS-triggered release. Melatonin (MLT) electrophile p-benzoquinone methide (p-QM) evidenced either cytoprotective or cytotoxic effects in biological systems, depending on dose, cellular...

The concise and convergent total syntheses of (+)- (−)-Fumimycin have been achieved by taking advantage strategies for the asymmetric aza-Friedel–Crafts reaction a highly substituted hydroquinone N-fumaryl ketimine generated from corresponding dehydroalanine. enantiomerically pure natural product its enantiomer were prepared in seven steps 22% overall yield employing both enantiomers BINOL-derived chiral phosphoric acid (CPA) catalyst.

N-Acetyl ketimine generated from methyl 2-acetamidoacrylate was explored to develop an unprecedented domino aza-Friedel-Crafts/lactonization reaction with naphthols and phenols (including 5-hydroxyindoles). This novel method requires a catalyst loading of only 5 mol % phosphoric acid provides new series 3-NHAc-naphtho- benzofuranone derivatives bearing tetra-substituted stereogenic centers in moderate-to-good yields. The enantioselective variant using BINOL-derived acids also 1-naphthol,...

Oxindoles react with <italic>N</italic>-acetyl amino alcohols to form tryptamine-derived oxindoles, whereas analogous reactions <italic>N</italic>-alkyl lead lactam formation <italic>via</italic> a relatively mild borrowing hydrogen process.

An efficient and practical approach for the synthesis of all four stereoisomers MT(2) melatonin receptor ligand 4-phenyl-2-propionamidotetralin (4-P-PDOT), each in enantiomerically pure form (ee > 99.9%), was developed. The strategy involved an optical resolution procedure key precursor (±)-4-phenyl-2-tetralone with unusual resolving agent (S)-mandelamide, through formation dihydronaphtalene-spiro-oxazolidin-4-one diastereomers. Interestingly, NMR experimental observations combination...

N-anilinoethylamides are a class of melatoninergic agents with the aniline portion mimicking indole ring natural ligand and ethylamide chain reproducing that melatonin. The simplest compound in this class, N-{2-[(3-methoxyphenyl)methylamino]ethyl}acetamide (UCM793), has nanomolar binding affinity for MT1 MT2 membrane receptors. To explore effect conformation on receptor binding, methyl group was inserted methylene alpha or beta to amide nitrogen conformational equilibria were investigated by...

The mechanism by which pentylenetetrazole provokes convulsions in animals has been investigated measuring its influence vitro on the activities of several enzymes glutamate metabolism rat brain homogenates. Pentylenetetrazole does not affect specific glutamine synthetase, glutaminase, or decarboxylase; it inhibits those dehydrogenase and aspartate aminotransferase, stimulates that γ-aminobutyric acid (GABA) aminotransferase. overall consequence action these should be an increase...

Melatonin is an endogenous molecule involved in many pathophysiological processes. In addition to the control of circadian rhythms, its antioxidant and neuroprotective properties have been widely described. Thus far, different bivalent compounds composed by a melatonin linked another agent were synthesized tested for their ability block neurodegenerative processes vitro vivo. To identify novel class potential compounds, we prepared series ligands, which prototypic melatonergic ligand...

Abstract The MT 2 ‐selective melatonin receptor ligand UCM765 ( N ‐(2‐((3‐methoxyphenyl)(phenyl)amino)ethyl)acetamide), showed interesting sleep inducing, analgesic and anxiolytic properties in rodents, but suffers from low water solubility modest metabolic stability. To overcome these limitations, different strategies were investigated, including modification of metabolically liable sites, introduction hydrophilic substituents design more basic derivatives. Thermodynamic solubility,...

The growing importance of structurally diverse and functionalized enantiomerically pure unnatural amino acids in the design drugs, including peptides, has stimulated development new synthetic methods. This study reports challenging direct asymmetric alkylation cyclic ketones with dehydroalanine derivatives via a conjugate addition reaction for synthesis enantiopure ketone-based α-unnatural acids. key to success was bifunctional primary amine-thiourea catalyst that combines H-bond-directing...

Abstract A regioselective hydroboration and hydrosilylation of dehydroalanines is presented.

Abstract A single‐step practical synthesis of dehydroalanine (Dha) derivatives from commercially available starting materials is reported. The approach comprises a Brønsted acid‐catalyzed three‐component condensation reaction pyruvic acid, an alcohol/thiol, and amide/carbamate. This protocol provided access to several Dha derivatives, including novel chiral version modified with diverse functional groups, which might be useful for further transformations in the construction more complex molecules.

Abstract The selective indole alkylation reaction applying the Ir‐catalyzed‐borrowing hydrogen methodology and using amino alcohols (II), (V), (VII) as suitable nitrogen‐containing electrophiles is reported.

Fluorescent ligands are imperative to many facets of chemical biology and medicinal chemistry. Herein, we report the syntheses two fluorescent melatonin-based derivatives as potential melatonin receptors. The compounds, namely, 4-cyano 4-formyl (4CN-MLT 4CHO-MLT, respectively), which differ from by only two/three atoms that very compact in size, were prepared using selective C3-alkylation indoles with N-acetyl ethanolamines involving "borrowing hydrogen" strategy. These compounds exhibit...

Abstract The method can be used to synthesize melatonin (VIII) and luzindole (IIIe), an MT 2 receptor antagonist.