ABSTRACT
We developed a concise protocol for the synthesis of ellipticine quinone from the appropriate 3-iodoindole-2-carbaldehydes in four steps. The key step is the construction of carbazole-1,4-quinone through tandem Ring-Closing Metathesis (RCM) and dehydrogenation under oxygen atmosphere. Therefore, the ellipticine quinone analogs possessing substitution at the 8- and/or 9-positions were synthesized using this method. In total, 14 compounds were evaluated for antiproliferative activity against HCT-116 and HL-60 cell lines; 9-nitroellipticine quinone was found to have superior activity compared to calothrixin B.
Subject(s)
Antineoplastic Agents/pharmacology , Benzoquinones/pharmacology , Ellipticines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Benzoquinones/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Ellipticines/chemistry , Humans , Molecular Structure , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
We report a convenient synthesis of carbazole-1,4-quinone alkaloid koeniginequinones A and B using a tandem ring-closing metathesis with the dehydrogenation reaction sequence under an O2 atmosphere as an important step. Using this method, carbazole-1,4-quinones substituted at the 5-, 6-, 7-, and/or 8-positions have been synthesized. Moreover, 24 compounds, including koeniginequinones A and B, have been evaluated for their antiproliferative activity against HCT-116 and HL-60 cells, and the 6-nitro analog exhibited the most potent activity against both tumor cell types.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Carbazoles/chemical synthesis , Carbazoles/pharmacology , Quinones/chemical synthesis , Quinones/pharmacology , Antineoplastic Agents/chemistry , Carbazoles/chemistry , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , HCT116 Cells , HL-60 Cells , Humans , Quinones/chemistryABSTRACT
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.
Subject(s)
Indole Alkaloids/chemistry , Monoterpenes/chemistry , Indole Alkaloids/chemical synthesis , Indole Alkaloids/isolation & purification , Indole Alkaloids/pharmacology , Molecular Structure , Monoterpenes/chemical synthesis , Monoterpenes/isolation & purification , Monoterpenes/pharmacologyABSTRACT
9,10-Phenanthrenequinone (9,10-PQ) is one of the most abundant quinones among diesel exhaust particulates. Recent data have suggested that quinones induce apoptosis in immune, epithelial and tumor cells, leading to respirator illness; however, the mechanisms by which quinones induce apoptosis and the structure required for this remain unknown. We studied the antitumor activity of 9,10-PQ analogs against two human tumor cell lines, HCT-116 colon tumor cells and HL-60 promyelocytic leukemia cells. The loss of the cis-orthoquinone unit in 9,10-PQ abrogated its ability to induce apoptosis in the two tumor cell lines, and the LC50 values of these analogs were indicated over 10 µM. An analog of 9,10-PQ in which the biaryl unit had been deleted displayed a reduced ability to induce tumor cell apoptosis, while the analogs 1,10-phenanthroline-5,6-dione (9) and pyrene-4,5-dione (10), which also had modified biaryl units, exhibited increased tumor cell apoptotic activity. The cis-orthoquinone unit in 9,10-PQ was identified as essential for its ability to induce apoptosis in tumor cells, and its biaryl unit is also considered to influence orthoquinone-mediated apoptotic activity.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Neoplasms/drug therapy , Phenanthrenes/pharmacology , Antineoplastic Agents/chemistry , HCT116 Cells , HL-60 Cells , Humans , Inhibitory Concentration 50 , Molecular Structure , Phenanthrenes/chemical synthesis , Phenanthrenes/chemistryABSTRACT
A one-pot approach to 3,3'-bisindolylmethane derivatives from nitrobenzene derivatives through the Bartoli indole synthesis was developed, in which the acid used to quench the reaction markedly affected its outcome. Quenching the reaction with concd HCl produced 3,3'-bisindolylmethane in contrast to the formation of 7-substituted indole by quenching with NH4Cl.
Subject(s)
Indoles/chemical synthesis , Catalysis , Cyclization , Indoles/chemistry , Molecular StructureABSTRACT
A new cleavage reaction of carbon-carbon triple bonds proceeds efficiently with NIS and TMSN3, giving the corresponding nitriles in moderate to good yields.
Subject(s)
Alkynes/chemistry , Carbon/chemistry , Gold/chemistry , Nitriles/chemistry , Nitriles/chemical synthesis , CatalysisABSTRACT
Covering: 2010-2011. Previous review: Nat. Prod. Rep. 2010, 27, 1630-1680This review covers the literature on simple indole alkaloids and those with a non-rearranged monoterpenoid unit from the beginning of 2010 up to the end of 2011, which includes newly isolated alkaloids, structure determinations, total syntheses and biological activities.
Subject(s)
Indole Alkaloids/chemistry , Monoterpenes/chemistry , Indole Alkaloids/isolation & purification , Molecular Structure , Monoterpenes/isolation & purificationABSTRACT
We synthesized calothrixin B using our developed biomimetic method and derived N-alkyl-calothrixins A and B. The in vitro antimalarial activity of the calothrixin derivatives, including calothrixins A and B, against the Plasmodium falciparum FCR-3 strain was evaluated. All test compounds exhibited antimalarial activity over a concentration range of 6.4×10(-6)-1.2×10(-7) M.
Subject(s)
Antimalarials/chemical synthesis , Indole Alkaloids/chemistry , Alkylation , Antimalarials/pharmacology , Indole Alkaloids/pharmacology , Molecular Structure , Plasmodium falciparum/drug effects , Structure-Activity RelationshipABSTRACT
Concise and efficient syntheses of various trans-2,3-disubstituted-2,3-dihydro-4-quinolones have been achieved via tandem Hofmann-type rearrangement of 2-alkynylbenzamides, nucleophilic addition of alcohols to the isocyanate intermediates, intermolecular [2+2]-cycloaddition with carbon-carbon triple bonds and aldehydes, and intramolecular aminocyclization of nitrogen of carbamates to the α,ß-unsaturated ketones.
Subject(s)
4-Quinolones/chemistry , 4-Quinolones/chemical synthesis , Carbamates/chemistry , Alkenes/chemistry , Catalysis , Cyclization , Ketones/chemistry , Molecular Structure , StereoisomerismABSTRACT
The concise total synthesis of calothrixins A and B has been accomplished by utilizing the one-pot formation of hexatriene as a key intermediate via the palladium-catalyzed tandem cyclization/cross-coupling reaction of triethyl(indol-2-yl)borate. In another key transformation, the indolo[3,2-j]phenanthridine core was prepared in high yield via Cu(I)-mediated 6π-electrocyclization.
Subject(s)
Indole Alkaloids/chemical synthesis , Catalysis , Copper/chemistry , Cyclization , Molecular Structure , Palladium/chemistryABSTRACT
Starting from ortho-alkynylbenzaldehydes and ortho-alkynylanilines, In(OTf)3-catalyzed synthesis of ring-condensed heteroaromatic compounds was developed via a domino intramolecular nucleophilic attack/intermolecular cycloaddition/dehydration reaction.
Subject(s)
Benzaldehydes/chemistry , Heterocyclic Compounds/chemistry , Indium/chemistry , Sulfanilic Acids/chemistry , Catalysis , Molecular StructureABSTRACT
The preparation of 2',3'-epimino-carbocyclic analogues of adenosine is reported. The reaction of p-tosyl azide with N-substituted 2-azabicyclo[2.2.1]hept-5-en-3-one (ABH) (1a) provided aziridine-fused ABH (2), which was converted to 2',3'-epimino-carbocyclic nucleosides (11).
Subject(s)
Adenosine/analogs & derivatives , Adenosine/chemical synthesis , Nucleosides/chemistry , Azides/chemistry , Lactams/chemistryABSTRACT
The reaction of 1-methoxymethylindolylborates 2 with electrophiles in the presence of benzaldehyde enabled the novel construction of tri-substituted indoles in a 'one-pot' procedure.