β-Carboline Alkaloids, Part 8.<sup>1</sup>Regioselective Homolytic Acetylation of β-Carbolines

Bracher, Franz; Daab, Jochen C.

doi:10.1080/00397919508011768

Cited by 15 publications

(10 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under mild conditions no conversion was seen, upon heating the bromoketone decomposed, without giving any identifiable product (Scheme 1). Finally, we succeeded in preparation of norisotuboflavine (1a) in 34% yield by reacting 1-acetyl-b-carboline (5) 14,17 with N-acetylbenzotriazole (6a) 21,22 and 2 equiv of LDA in THF at 0e20 C, obviously via the 1,3-diketone 3a. In the same manner, alkaloid isotuboflavine (1b) was obtained from methyl ketone 5 and Npropanoylbenzotriazole (6b) 21 in 16% yield (Scheme 1).…”

Section: 3-diketone Routementioning

confidence: 99%

“…Cyclization of the diketones was expected to give the canthin-4-one scaffold (1). In a second approach we intended to find alternatives to the 1-acyl-b-carboline intermediates, since these are accessible only by using laborious methods (radical reactions, 8,14,15 organometallic chemistry 16 ) or expensive organostannane building blocks. 17 1-Isoxazolyl-b-carbolines (D) were considered as versatile intermediates, which should give primary enaminoketones (E) upon reductive ring cleavage, 18 and the latter were expected to cyclize to the canthin-4-one ring system in a similar manner as known for tertiary enaminoketone intermediates (B) (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

New approaches to the synthesis of canthin-4-one alkaloids and synthetic analogues

Tremmel

Bracher

2015

Tetrahedron

View full text Add to dashboard Cite

Section: 3-diketone Routementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New approaches to the synthesis of canthin-4-one alkaloids and synthetic analogues

Tremmel

Bracher

2015

Tetrahedron

View full text Add to dashboard Cite

“…[31][32][33][34][35][36] The title compound 2 was achieved from 2f by the method analogus with 1f prepared from 1d mentioned above.…”

Section: -Aminosulfonyl-1-carbamoyl-3-(1h-benzo[d]imidazol-2-yl)-β-cmentioning

confidence: 99%

Synthesis and Structure of the β-Carboline Derivatives and Their Binding Intensity with Cyclin-Dependent Kinase 2

Wang

Jin

Lin

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Series of 3-substituted of 6-aminosulfonyl-β-carbolines were designed and synthesized. In addition, the binding mode of these β-carboline derivatives with cyclin-dependent kinase 2 (CDK2) was studied by means of fluorescence measurements and molecular docking calculation. The results showed that replacement of 3-cyclohexylmethoxy group will increase the hydrophobic binding interaction with the deep hydrophobic pocket of CDK2 correlate to the higher binding intensity.Key words cyclin-dependent kinase 2; β-carboline; synthesis; molecular docking; fluorescence It is well known that the phases of the cell cycle are driven by cyclin-dependent kinases (CDKs). Upon complexation with its activating proteins, cyclin E or cyclin A, cyclin-dependent kinase 2 (CDK2) modulates the activity of many cellular substrates via phosphorylation on serine (Ser) and/or threonine (Thr) residues.1-4) Abnormal CDK control of the cell cycle has been strongly linked to the molecular pathology of cancer. 5)The importance of CDK2 for cell cycle progression has led to an active pursuit of small molecule inhibitors of this enzyme as a possible treatment against cancer and other hyper-proliferative disorders.6-9) All CDK inhibitors, identified so far, function by competing with ATP for binding to the catalytic site. Actually several CDK inhibitors have entered clinical evaluation for the treatment of cancer, including flavopiridol, amino-thiazole compound.10) In our program to develop CDK2 inhibitors, we recently investigate the β-carboline alkaloids containing a planar tricyclic system as a large group of naturally-occurring and synthetic alkaloids, [11][12][13][14] which has a broad spectrum of biochemical effects and pharmaceutical properties. These compounds have been shown to intercalate into DNA, to inhibit CDK, topisomerase and monoamine oxidase, and to interact with benzodiazepine receptors (BZ), 5-hydroxy serotonin receptors (5-HT), dopamine (DA) and imidazoline receptors. [15][16][17][18][19][20][21][22][23] Inspired by these results, our research group recently focused on first of all, using a structure-guided strategy based on CDK2 as appropriate means to generate potent CDK2 inhibitors; then to synthesize disubstituted β-carbolines and to complete their biological evaluation study. As a part of our systematic work, in this paper, structure modification of β-carboline based on increasing its hydrophobic nature has been adopted. Herein we reported the design and synthesis of series of 3-substituted of 6-aminosulfonyl-β-carbolines. Series of 3-substituted compounds with different hydrophobic groups (Chart 1) were synthesized and one of their structures was elucidated with X-ray crystal analysis. The new derivatives were prepared following the reaction sequences depicted in Charts 2-4. Their binding intensity with CDK2 was measured by fluorescence spectroscopy. ExperimentalSynthesis The target compounds were prepared using the reaction sequence. All the chemical structures of the synthesized compounds were confirmed by spectroscopic me...

show abstract

“…In contrast, 1-acyl-β-carbolines cannot be readily prepared by the classical methods. Some time ago we published new strategies for the synthesis of 1-acyl-β-carbolines starting from 1-bromo-β-carboline (7) [3] or from norharmane (4) [1] following the Minisci reaction [4].…”

mentioning

confidence: 99%

“…Since arenarine A (1) is simply a α-methoxy derivative of the readily available 1-acetyl-β-carboline (3) [1,3], we envisaged to prepare this alkaloid by regioselective homolytic acylation of norharmane (4) with an appropriate aldehyde in close analogy to the synthesis of 3 [1]. This radical reaction worked well with various aromatic and aliphatic aldehydes [6], so we planned to use chloroacetaldehyde as a source of the acyl radical.…”

mentioning

confidence: 99%

β‐Carboline alkaloids 9 [1]. Total synthesis of the β‐carboline alkaloids arenarine A and (±)arenarine B

Bracher

Puzik

2004

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

The first total synthesis of the β-carboline alkaloids arenarine A (1) and arenarine B (2) is described. Methanolysis of the α-bromoketone 9 gives 1 in good yield. Alternatively 1 can be obtained from the diazoketone 11 with boron trifluoride/methanol in poor yield. Reduction of 1 with sodium borohydride gives racemic arenarine B (2). Regioselective homolytic methylation of norharmane (4) with tert-butyl hydroperoxide/ferrous sulfate gives the alkaloid harmane (6).

show abstract

β-Carboline Alkaloids, Part 8.¹Regioselective Homolytic Acetylation of β-Carbolines

Cited by 15 publications

References 13 publications

New approaches to the synthesis of canthin-4-one alkaloids and synthetic analogues

New approaches to the synthesis of canthin-4-one alkaloids and synthetic analogues

Synthesis and Structure of the β-Carboline Derivatives and Their Binding Intensity with Cyclin-Dependent Kinase 2

β‐Carboline alkaloids 9 [1]. Total synthesis of the β‐carboline alkaloids arenarine A and (±)arenarine B

Contact Info

Product

Resources

About

β-Carboline Alkaloids, Part 8.1Regioselective Homolytic Acetylation of β-Carbolines

Cited by 15 publications

References 13 publications

New approaches to the synthesis of canthin-4-one alkaloids and synthetic analogues

New approaches to the synthesis of canthin-4-one alkaloids and synthetic analogues

Synthesis and Structure of the β-Carboline Derivatives and Their Binding Intensity with Cyclin-Dependent Kinase 2

β‐Carboline alkaloids 9 [1]. Total synthesis of the β‐carboline alkaloids arenarine A and (±)arenarine B

Contact Info

Product

Resources

About

β-Carboline Alkaloids, Part 8.¹Regioselective Homolytic Acetylation of β-Carbolines