Search

The O4-benzo[c]phenanthridine alkaloids exhibit potent antiproliferative activity against cancer cells, which is derived from their ability to inhibit of topoisomerase I and II. It has been reported that in the alkaloids a cationic quaternary ammonium atom, which results in resonance effects between ring A and B, is necessary for increased antiproliferative activity. These findings indicate the role of their substituents at ring A on inhibition of tumor cell proliferation. In the present study, we systematically assessed the cytotoxic activities of naturally occurring alkaloids and their derivatives containing various ring A substituents against two tumor cell lines, HCT-116 colon tumor cells and HL-60 promyelocytic leukemia cells. Among the cationic iminium alkaloids, which displayed more potent activity than the corresponding neutral derivatives, and the 7,8-oxygenated benzo[c]phenanthridine alkaloids, chelerythrine and NK109, exhibited stronger antiproliferative activity than the 8,9- and 9,10-oxygenated alkaloids. The activity of cationic iminium alkaloids could be correlated with the bond lengths of their ring A substituents and the electrostatic potentials of their ammonium molecules by DFT calculation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Antioxidant activities of 3-oxygenated and 3,4-dioxygenated carbazole alkaloids and their related carbazoles were comprehensively evaluated. In all assay systems, the 3,8-dihydroxycarbazoles carbazomadurin A (2) and B (3), and their synthetic precursors 2a and 3a exhibited higher antioxidant activities than the 3-monohydroxycarbazoles carazostatin (1), and the synthetic precursors 4a and 4b of carquinostatin A (4). In particular, 2a and 3a exhibited strong scavenging activities due to the reducing ability of formyl group at the C-5 position of carbazoles. The results suggest that these compounds could serve as useful clues for designing and developing novel antioxidants., (Copyright © 2014. Published by Elsevier Ltd.)

Concise syntheses of 9-methoxyellipticine, 3,4-dihydroellipticine (µ-alkaloid D), 1,2,3,4-tetrahydroellipticine, 2-methyl-1,2,3,4-tetrahydroellipticine, olivacine, 3,4-dihydroolivacine, (±)-guatambuine, and (±)-janetine were developed starting from hexatriene intermediates readily obtained by Pd-catalyzed tandem cyclization/cross-coupling reaction of indolylborates. The route enables the facile construction of pyrido[4,3- b]carbazoles by Cu-catalyzed 6π-electrocyclization and subsequent transformation of the pyridocarbazole intermediates into pyrido[4,3- b]carbazole alkaloids. [ABSTRACT FROM AUTHOR]

Covering: 2012 to 2013. Previous review: Nat. Prod. Rep., 2013, 30, 694–752 This review covers the literature on simple indole alkaloids and those with a nonrearranged monoterpenoid unit from the beginning of 2012 up to the end of 2013, which includes newly isolated alkaloids, structure determinations, total syntheses and biological activities. [ABSTRACT FROM AUTHOR]

The total syntheses of the neuronal cell-protecting carbazole alkaloids carbazomadurin A and ( S)-(+)-carbazomadurin B were achieved. The key step of the synthesis of the polysubstituted carbazole rings included an allene-mediated electrocyclic reaction of the 6π-electron system that involved the indole 2,3-bond. The cleavage of the alkoxy groups of the resulting 3-ethoxy-8-isopropoxycarbazole successfully gave the 3,8-dihydroxycarbazole, which was converted into the 3,8-bis(OSEM)-carbazole (SEM = 2-trimethylsilylethoxymethyl). A Suzuki-Miyaura cross-coupling reaction of the 3,8-bis(OSEM)-carbazole with the corresponding alkenyl pinacol borates afforded the 1-alkenylcarbazoles, which were treated with tetra- n-butylammonium fluoride (TBAF) followed by reduction with NaBH4 to provide carbazomadurin A and ( S)-(+)-carbazomadurin B, respectively. [ABSTRACT FROM AUTHOR]

The neurobiological mechanism underlying the negative motivational component of withdrawal from acute opiate dependence is far from understood.Our objectives were to determine whether the glutamatergic system is involved in the motivational component of morphine withdrawal in acutely dependent rats and such an involvement is associated with dopaminergic neurotransmission.We examined the effects of various kinds of glutamate receptor antagonists on conditioned place aversion (CPA) induced by naloxone-precipitated withdrawal from a single morphine exposure 24 h before. Furthermore, the influence of pretreatment with the dopamine receptor antagonist haloperidol on those effects of glutamate receptor antagonists was also investigated.CPA was attenuated in a dose-dependent manner by all glutamate receptor antagonists examined including the NMDA receptor antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine maleate (MK-801) and phencyclidine hydrochloride (PCP), AMPA receptor antagonist 1-(4-aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466), and metabotropic receptor antagonists (±)-2-amino-3-phosphonopropionic acid (AP-3) and (±)-α-methyl-4-carboxyphenylglycine (MCPG). The effects of MK-801, GYKI 52466 and MCPG were blocked by haloperidol.These results suggest that the glutamatergic system involving multiple classes of receptors plays a role in the motivational component of withdrawal from acute morphine dependence, and the function of the glutamatergic system would be closely associated with dopaminergic neurotransmission.British Journal of Pharmacology (2005) 145, 751–757. doi:10.1038/sj.bjp.0706228; published online 9 May 2005 [ABSTRACT FROM AUTHOR]

The synthesis of alkaloid (I) is achieved in six steps in 60% overall yield from dihydroxymethylchromanone. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article "Total Synthesis of the Neuronal Cell-Protecting Carbazole Alkaloids Carbazomadurin A (I) and (S)-(+)-Carbazomadurin B (II)" by Y. Hieda, T. Choshi and others, published in the "European Journal of Organic Chemistry" in 2013.

Abstract: Total syntheses of the des-N-methyl (nor) type of benzo[c]phenanthridine alkaloids 1a–f and 19 and benzo[c]phenanthridine alkaloids, chelerythrine (2d), and broussonpapyrine (2f) were achieved. The key step was the construction of tetracyclic 10,11-dihydrobenzo[c]phenanthridines using a microwave-assisted electrocyclic reaction of the 2-cycloalkenylbenzaldoxime methyl ether 4 as an aza 6π-electron system, which was derived in two steps from a Suzuki–Miyaura cross-coupling reaction of 2-bromobenzaldehyde 6 with 2-(3,4-dihydro-6,7-methylenedioxynaphthyl)boronic acid pinacol ester 7. In addition, the exact structure of broussonpapyrine (2f) (2,3,9,10-tetraoxygenated type) was determined to be chelerythrine (2d). [ABSTRACT FROM AUTHOR]

Abstract: A new and versatile synthetic route to a benzophenanthridine alkaloid was developed by a bond formation between C4b and N5 on the benzo[c]phenanthridine nucleus, using a microwave-assisted electrocyclic reaction of the aza 6π-electron system. This strategy was successfully used to synthesize nornitidine (1b), noravicine (1d), and isodecaline (1f). [Copyright &y& Elsevier]

Cu-catalyzed 6π-electrocyclization of triene-substrates of type (I) provides a facile access to pyrido[4,3-b]carbazoles, which represent advanced intermediates for the construction of various ellipticine and olivacine alkaloids. [ABSTRACT FROM AUTHOR]

The alkaloid tryptanthrin (IIa) is further converted into the natural products phaitanthrin A (IXa), phaitanthrin B (IXb), and cruciferane (X). [ABSTRACT FROM AUTHOR]

In this study, we achieved the total synthesis of carbazole alkaloid mukoenine A through a seven-step sequence involving the construction of a carbazole framework using the electrocyclization of a 6π-electron system including an allene intermediate as the key step. Subsequently, the synthesis of pyrano[3,2- a ]carbazole alkaloid girinimbine was achieved by the construction of the pyran ring via selenoetherification of the o-allylic phenol moiety of mukoenine A. [Display omitted] • The total synthesis of mukoenine A has been accomplished via a seven-step sequence. • Girinimbine was synthesized by the construction of the pyran ring via mukoenine A. • The carbazole framework was constructed by the allene-mediated electrocyclization. [ABSTRACT FROM AUTHOR]

Review: 265 refs. [ABSTRACT FROM AUTHOR]

The total synthesis of renierone, mimocin, renierol, renierol acetate, renierol propionate, and 7-methoxy-1,6-dimethylisoquinoline-5,8-dione was successfully achieved by the regioselective oxidation of 5-oxygenated isoquinoline. The synthetic method of the 5-oxygenated isoquinoline is based on the thermal electrocyclic reaction of 1-azahexatriene system involving the benzene 1,2-bond. [Copyright &y& Elsevier]

In this study, the total syntheses of 1,3,4-trisubstituted carbazole alkaloid clausamine E was accomplished via an eight-step sequence using construction of the 1,4-dioxygenated carbazole framework based on the cyclocarbonylation between 3-iodo-2-(prop-2-enyl)indole and CO (1 atm) in the presence of tributyl(vinyl)tin and a Pd catalyst. Image 1 • The total synthesis of clausamine E has been accomplished via an eight-step sequence. • Synthesis of 1,4-dioxygenated carbazoles by Pd-catalyzed cyclocarbonylation. • This method could be used as a versatile method to synthesize substituted carbazoles. [ABSTRACT FROM AUTHOR]

• The enantioselective total synthesis of (+)-asiaticumine A has been accomplished. • The construction of phenanthridine framework by MW-assisted electrocyclization. • The synthesis of 1,2-dihydroxyethyl moiety by Sharpless asymmetric dihydroxylation. • Its absolute configuration was determined to be S by Mosher's method. In this study, the first asymmetric enantioselective total syntheses of (+)-asiaticumine A (2) and its enantiomer were accomplished through a seven-step sequence using the bond formation between the C4a and N5 positions of the phenanthridine framework based on the microwave-assisted electrocyclization of cyclohexenylbenzaldoxime methyl ether as an aza 6π-hexatriene system followed by the Sharpless asymmetric dihydroxylation as the key step. In addition, the absolute configuration of natural (+)- 2 was determined to be S by Mosher's method. [ABSTRACT FROM AUTHOR]