Synthesis Of Β-carbolines Research Articles

PhI(OAc)2-mediated one-pot oxidative decarboxylation and aromatization of tetrahydro-β-carbolines: synthesis of norharmane, harmane, eudistomin U and eudistomin I.

Iodobenzene diacetate was employed as a mild and efficient reagent for one-pot oxidative decarboxylation of tetrahydro-β-carboline acids and dehydrogenation of tetrahydro-β-carbolines to access the corresponding aromatic β-carbolines. To the best of our knowledge this is the first synthesis of β-carbolines via a one-pot oxidative decarboxylation at ambient temperature. The utility of this protocol has been demonstrated in the synthesis of β-carboline alkaloids norharmane (2o), harmane (2p), eudistomin U (9) and eudistomin I (12).

An efficient one-pot decarboxylative aromatization of tetrahydro-β-carbolines by using N-chlorosuccinimide: total synthesis of norharmane, harmane and eudistomins

A mild one-pot synthesis of β-carbolines from their tetrahydro-β-carboline acids has been developed via decorboxylative aromatization using N-chlorosuccinimide (NCS).

An Improved Synthesis of β-Carboline and Azepino-and Azocino[3,4-b]Indole Derivatives from Lactams

The Vilsmeier formylation of butyrolactam, N-methylbutyrolactam, N-methylvalerolactam, and N-methylcaprolactam followed by treatment with aryl hydrazines afforded the 2,3,4,9-tetrahydro-1Н-β-carbolin-1-ones, 3,4,5,10-tetrahydroazepino[3,4-b]indol-1(2Н)-ones, and 2,3,4,5,6,11-hexahydro-1Н-azocino[3,4-b]indol-1-ones. The synthesis was performed as a one-pot process without isolating the intermediate α-formyl lactams.

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

A novel synthetic methodology has been developed for the synthesis of dihydro-β-carboline derivatives employing oxidative amidation–Bischler–Napieralski reaction conditions using tryptamine and 2,2-dibromo-1-phenylethanone as key starting materials. A number of dihydro-β-carboline derivatives have been synthesized in moderate to good yields using this methodology. Attempts were made towards the conversion of these dihydro-β-carbolines to naturally occurring eudistomin alkaloids.

Synthesis of β-carboline–benzimidazole conjugates using lanthanum nitrate as a catalyst and their biological evaluation

A series of β-carboline-benzimidazole conjugates bearing a substituted benzimidazole and an aryl ring at C3 and C1 respectively were designed and synthesized. The key step of their preparation was determined to involve condensation of substituted o-phenylenediamines with 1-(substituted phenyl)-9H-pyrido[3,4-b]indole-3-carbaldehyde using La(NO3)3·6H2O as a catalyst and their cytotoxic potential was evaluated. Conjugates 5a, 5d, 5h and 5r showed enhanced cytotoxic activity (GI50 values range from 0.3 to 7.1 μM in most of the human cancer cell lines) in comparison to some of the previously reported β-carboline derivatives. To substantiate the cytotoxic activity and to understand the nature of interaction of these conjugates with DNA, spectroscopy, DNA photocleavage and DNA topoisomerase I inhibition (topo-I) studies were performed. These conjugates (5a, 5d and 5r) effectively cleave pBR322 plasmid DNA in the presence of UV light. In addition, the effect of these conjugates on DNA Topo I inhibition was studied. The mode of binding of these new conjugates with DNA was also examined by using both biophysical as well as molecular docking studies, which supported their multiple modes of interaction with DNA. Moreover, an in silico study of these β-carboline-benzimidazole conjugates reveals that they possess drug-like properties.

Three-step synthesis of an annulated β-carboline via palladium catalysis

The synthesis of β-carbolines is a mature field, yet new methods are desirable to introduce new functionality onto the core scaffold. We describe the incorporation of an additional fused ring onto the β-carboline via a novel palladium-catalyzed, one-pot Sonogashira coupling/intramolecular [2+2+2] cyclization. This method generates three rings in one flask and produces an annulated β-carboline in 80% yield. A preliminary mechanistic study into the sequence of events is described, which confirms an unprecedented catalytic role for palladium.

A Cascade Coupling Strategy for One‐Pot Total Synthesis of β‐Carboline and Isoquinoline‐Containing Natural Products and Derivatives

Multi-birds with one stone: A cascade coupling strategy was developed for the synthesis of β-carbolines. The method can direct the synthesis of β-carboline and isoquinoline-containing natural products with high yields. Moreover, this protocol can also be further applied towards the total synthesis of natural products fascaplysin and papaverin (see scheme).

Preparation and antiprotozoal evaluation of promising β-carboline alkaloids

The synthesis of β-carbolines and their in vitro antiplasmodial and antileishmanial activities were described herein. These molecules have also been studied concerning their in vitro cytotoxicity toward the human cell line THP1, in order to calculate their respective selectivity indexes (SI). Among the 20 tested molecules, four exhibited significant antiplasmodial activity on the W2 multi-resistant Plasmodium falciparum strain (0.7<IC50<1.7μM), in comparison with two references drugs (chloroquine and doxycycline), and a low cytotoxicity. These β-carbolines were also evaluated concerning their in vitro antileshmanial activity on Leishmania donovani promastigotes, permitting to identify an antileshmanial hit compound, displaying quite promising activity (IC50=6.1μM) in comparison with amphotericin B and pentamidine chosen as reference drugs. Finally, structure–activity relationships were discussed, pointing out that molecules presenting a para-substituted phenyl moiety at position 1 of the β-carboline ring displayed the best biological profile.

Intramolecular palladium-catalysed enolate arylation of 2- and 3-iodoindole derivatives for the synthesis of β-carbolines, γ-carbolines, and pyrrolo[3,4-b]indoles

The palladium-catalysed intramolecular α-arylation of carbonyl compounds with amino-tethered 2- and 3-iodoindoles provides a useful methodology for the synthesis of indolo-b-fused nitrogen heterocycles. A variety of substituted tetrahydro β- and γ-carbolines, and pyrrolo[3,4-b]indoles, have been prepared by means of this palladium-catalysed annulation process.

ChemInform Abstract: New One‐Pot Methodologies for the Modification or Synthesis of Alkaloid Scaffolds

AbstractReview: 38 refs.

New one-pot methodologies for the modification or synthesis of alkaloid scaffolds.

There are several avenues by which promising bioactive natural products can be produced in sufficient quantities to enable lead optimization and medicinal chemistry studies. The total synthesis of natural products is an important, but sometimes difficult, approach and requires the development of innovative synthetic methodologies to simplify the synthesis of complex molecules. Various classes of natural product alkaloids are both common and widely distributed in plants, bacteria, fungi, insects and marine organisms. This mini-review will discuss the scope, mechanistic insights and enantioselectivity aspects of selected examples of recently developed one-pot methods that have been published in 2009 for the synthesis of substituted piperidines, quinolizidines, pyrrolidines, hexahydropyrrolizines, octahydroindolizines and γ-lactams. In addition, progress on the synthesis of β-carboline (manzamine) alkaloids will also be discussed.

Synthesis of β-carbolines from aldehydes and ketones via the α-siloxy α,β-unsaturated esters

We report an efficient method for the synthesis of β-carbolines from α-siloxy α,β-unsaturated esters, which are accessible from a variety of aldehydes and ketones.

Facile and Efficient One-Pot Synthesis of β-Carbolines

Initial formation of tetrahydrocarboline 3 from tryptophan methyl ester 1 and aldehyde 2 by Pictet–Spengler reaction, followed by treatment with trichlorocyanuric acid, provides a facile and efficient route for a one-pot synthesis of β-carbolines with excellent yields.

Simple synthesis of γ-carbolines

indoles, γ-carbolines, Bischler-Napieralski reaction, Leuckart-Wallach reaction. γ-Carboline derivatives and their hydrogenated analogs are less popular than the structurally isomeric β-carbolines [1]. None the less, γ-carbolines are of interest pharmacologically since compounds having various forms of biological activity are found in this class [2-5] and so the development of novel routes of synthesizing the γ-carboline framework is timely. Thanks to the availability of tryptamine derivatives, electrophilic cyclizations of the Pictet-Spengler, Bischler-Napieralski and related type processes are widely used for the synthesis of β-carbolines [1]. Analogous reactions amongst methods for preparing γ-carbolines [2, 6-9] occupy a modest placement [10, 11] and this is likely related to the lesser availability of the corresponding amines. In this work we report preliminary data regarding a novel synthesis of γ-carbolines in which the key stage is a Bischler-Napieralski reaction. As a result of a Leuckart-Wallach type reductive amination the indole

A direct synthesis of β-carbolines via a three-step one-pot domino approach with a bifunctional Pd/C/K-10 catalyst

A rapid, microwave-assisted synthesis of β-carbolines via a successive condensation/cyclization/dehydrogenation approach is described. This methodology involves the coupling of various tryptamines with aromatic aldehydes/glyoxals. The product imine undergoes a Pictet–Spengler cyclization followed by a final dehydrogenation to yield β-carbolines in a three-step domino reaction. The use of the bifunctional catalyst Pd/C/K-10 combined with microwave irradiation enabled the synthesis of β-carbolines in short reaction times and in good to excellent yields.

A mild and efficient route to 2-benzyl tryptamine derivatives via ring-opening of β-carbolines

We described a mild and easy method, in two steps, by which various benzyl groups were introduced in the C-2 position of tryptamine. The first step consisted on the synthesis of β-carbolines, starting from tryptamine derivatives, by a Pictet–Spengler reaction. Ring-opening of the β-carbolines, by hydrogenation, led to the desired 2-substituted benzyl tryptamine indole products. A supplementary step of alkylation could be realized to give N-alkyl-2-substituted benzyl tryptamine. During these reactions, nitrogen atoms require no step of protection.

A novel palladium-catalyzed synthesis of β-carbolines: application in total synthesis of naturally occurring alkaloids

Two naturally occurring β-carbolines, 6-methoxy-2-methyl-1,2,3,4-tetrahydro-β-carboline and bauerine A, have been prepared using a Stille-type coupling, followed by a palladium-phosphine catalyzed N-heteroannulation as the key steps.

Liquid-phase parallel synthesis of tetrahydro-β-carbolines

Parallel synthesis of β-carbolines on soluble polyethylene glycol (PEG-OH) support is demonstrated. One-pot condensation of polymer-bound tryptophan residues with various aldehydes and ketones has been carried out in the presence of p-TSA as a catalyst to deliver immobilized 1,2,3,4-tetrahydro-β-carbolines. Subsequent disengagement of the appendant from the polymer support afforded the desired products in good yield and acceptable purity.

S26.02 Acute polymorphous psychosis due to endogenic synthesis of β-carbolines

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Synthesis ofβ-carboline with the germatrane portion

The 1-oxo-3,3-dimethyl-6-(β-trichlorogermyl)ethyl-1,2,3,4-tetrahydroindolo[2,3-c]pyrylium salt, obtained by the acid-catalyzed acylation of 2-(indol-3-yl)dimedone with β-trichlorogermylpropionyl chloride and the subsequent reaction with ammonia and triethanolamine, was converted to the corresponding β-carboline with the germatrane portion.