An efficient and convenient method was developed for the one‐pot construction of the complex polycyclic heterocycles pyrrolo[1,2‐a:2′,1′‐c]‐/pyrido[2,1‐c]pyrrolo[1,2‐a]quinoxalinones from two simple starting materials via a gold(I)‐catalyzed domino reaction. This strategy presents an atom economical and environmentally friendly transformation, in which two new C N bonds and one new C C bond are formed in a one‐pot reaction process. 相似文献
A series of substituted indolo[2,1-a]isoquinolines and indolo[1,2-a]benzoxazines have been prepared, as melatonin analogues, to investigate the nature of the binding site of the melatonin receptor. Agonist and antagonist potency of all the analogues was measured using the [35S]GTPγS binding assay protocol. The binding affinity of the analogues were measured by competition binding studies against the human MT1 (hMT1) and MT2 (hMT2) receptors stably transfected in Chinese Hamster Ovarian (CHO) cells, using 2-[125I]-iodomelatonin, as a ligand. N-Acetyl 2-(10-methoxy-5,6-dihydroindolo[2,1-a]isoquinolin-12-yl)propyl-1-amine (12 a) binds strongly to both the hMT1 and hMT2 receptors, and shows a preference for the hMT2, as does its propanamido counterpart 12 b . The introduction of two methyl groups into their side chain, analogues 15 a and 1 5 b , leads to antagonism, in the case of the former, and drastically diminishes its hMT1 binding; an analogous profile is seen for 15 b , which, however, is a partial agonist. Introduction of chlorine or methoxy groups into ring 4 gives compounds, that are weakly binding, with a preference for MT2. Substitution of oxygen for carbon at position 5 gives the indolo[1,2-c]benzoxazines 33 , 36 a and b , that bind strongly to the human receptors, 33 , 36 b being potent agonists at the melatonin receptors, but do not discriminate between hMT1 and hMT2. 相似文献
A novel palladium‐catalyzed intramolecular tandem annulation method is presented for the synthesis of 3‐[5H‐dibenzo[b,e]azepin‐11(6H)‐ylidene]indolin‐2‐ones. This method allows the conversion of various 3‐[2‐(2‐iodobenzylamino)aryl]‐N‐arylpropiolamides to the corresponding 3‐[5H‐dibenzo[b,e]azepin‐11(6H)‐ylidene]indolin‐2‐ones through the diarylation of an alkyne. 相似文献
A direct diastereoselective synthesis approach of important 9H‐pyrrolo[1,2‐a]azepin‐9‐amines was established via base‐promoted [4+3] annulation between donor–acceptor reagents derived from 1H‐pyrrole‐2‐carbaldehydes and alkyl 2‐aroyl‐1‐chlorocyclopropanecarboxylates. This transition metal‐free domino reaction proceeded quickly under mild basic conditions, affording potentially bioactive azepine derivatives in moderate to high yields with high diastereoselectivities (up to >20:1).
The synthesis of hitherto unknown pyrrolo[2,1‐f][1,2,4]triazine C‐nucleosides is described. Structural variations (chlorine, bromine, iodine, and cyano groups) were introduced at position 7 of 4‐aza‐7,9‐dideazaadenine. In addition, pyrrolo[2,1‐f][1,2,4]triazine C‐nucleosides bearing a 2′‐deoxy‐, 2′,3′‐dideoxy‐, and 2′,3′‐dehydrodideoxyribose moiety were also prepared. Among these analogues, the pyrrolo[2,1‐f][1,2,4]triazine C‐ribonucleosides with either a hydrogen atom or cyano group at position 7 of the nucleobase displayed potent cytotoxic activity in a panel of various cancer cell lines. 相似文献
A new enantioselective α‐alkylation of α‐tert‐butoxycarbonyllactams for the construction of β‐quaternary chiral pyrrolidine and piperidine core systems is reported. α‐Alkylations of N‐methyl‐α‐tert‐butoxycarbonylbutyrolactam and N‐diphenylmethyl‐α‐tert‐butoxycarbonylvalerolactam under phase‐transfer catalytic conditions (solid potassium hydroxide, toluene, −40 °C) in the presence of (S,S)‐3,4,5‐trifluorophenyl‐3,3′,5,5′‐tetrahydro‐2,6‐bis(3,4,5‐trifluorophenyl)‐4,4′‐spirobi[4H‐dinaphth[2,1‐c:1′,2′‐e]azepinium] bromide [(S,S)‐NAS Br] (5 mol%) afforded the corresponding α‐alkyl‐α‐tert‐butoxycarbonyllactams in very high chemical (up to 99%) and optical yields (up to 98% ee). Our new catalytic systems provide attractive synthetic methods for pyrrolidine‐ and piperidine‐based alkaloids and chiral intermediates with β‐quaternary carbon centers. 相似文献
An efficient protocol has been developed for the methylenation of imidazo[1,2‐a]pyridines using dimethylacetamide (DMA) as methylene source in the presence of vanadyl acetylacetonate [VO(acac)2] as the catalyst and iodobenzene diacetate as the oxidant. The reaction involves coupling of sp3‐ and sp2‐hybridized carbons and proceeds through the formation of an iminium ion. A wide variety of imidazo[1,2‐a]pyridines were converted to bis(imidazo[1,2‐a]pyridin‐3‐yl)methanes in good to excellent yields. A gram‐scale reaction demonstrated the potential for the scale‐up processes.
A number of aza‐heterocyclic compounds, which share the 5,6‐dihydropyrrolo[2,1‐a]isoquinoline (DHPIQ) scaffold with members of the lamellarin alkaloid family, were synthesized and evaluated for their ability to reverse in vitro multidrug resistance in cancer cells through inhibition of P‐glycoprotein (P‐gp) and/or multidrug‐resistance‐associated protein 1. Most of the investigated DHPIQ compounds proved to be selective P‐gp modulators, and the most potent modulator, 8,9‐diethoxy‐1‐(3,4‐diethoxyphenyl)‐3‐(furan‐2‐yl)‐5,6‐dihydropyrrolo[2,1‐a]isoquinoline‐2‐carbaldehyde, attained sub‐micromolar inhibitory potency (IC50: 0.19 μm ). Schiff bases prepared by the condensation of some 1‐aryl‐DHPIQ aldehydes with p‐aminophenol also proved to be of some interest, and one of them, 4‐((1‐(4‐fluorophenyl)‐5,6‐dihydro‐8,9‐dimethoxypyrrolo[2,1‐a]isoquinolin‐2‐yl)methyleneamino)phenol, had an IC50 value of 1.01 μm . In drug combination assays in multidrug‐resistant cells, some DHPIQ compounds, at nontoxic concentrations, significantly increased the cytotoxicity of doxorubicin in a concentration‐dependent manner. Studies of structure–activity relationships and investigation of the chemical stability of Schiff bases provided physicochemical information useful for molecular optimization of lamellarin‐like cytotoxic drugs active toward chemoresistant tumors as well as nontoxic reversers of P‐gp‐mediated multidrug resistance in tumor cells. 相似文献
A mild, catalytic, atom economical synthesis of imidazo[1,2‐a]pyridines has been developed: catalytic dichloro(2‐pyridinecarboxylato)gold [PicAuCl2] in the presence of an acid produces a range of imidazo[1,2‐a]pyridines in good yields starting from alkynes and 2‐aminopyridine N‐oxides. This strategy is mild and foreseen to be of particular use for the installation of stereogenic centers adjacent to the imidazo[1,2‐a]pyridine ring without loss of enantiomeric excess.
Treatment of cyclobutanecarboxamide with bis(trifluoroacetoxy)iodobenzene, PhI(OCOCF3)2, resulted in the formation of 1‐pyrroline via Hofmann rearrangement of the former followed by in situ ring expansion reaction of the cyclobutylamine intermediate. Further elaboration of this methodology to the synthesis of 2,3‐dihydro‐1H‐pyrrolo[2,1‐a]isoquinolinium salts has also been described.
A library of 5‐methylindolo[3,2‐c]quinolones (IQc) with various substitution patterns of alkyldiamine side chains were evaluated for G‐quadruplex (G4) binding mode and efficiency. Fluorescence resonance energy transfer melting assays showed that IQcs with a positive charge in the heteroaromatic nucleus and two weakly basic side chains are potent and selective human telomeric (HT) and gene promoter G4 stabilizers. Spectroscopic studies with HT G4 as a model showed that an IQc stabilizing complex involves the binding of two IQc molecules (2,9‐bis{[3‐(diethylamino)propyl]amino}‐5‐methyl‐11H‐indolo[3,2‐c]quinolin‐5‐ium chloride, 3 d ) per G4 unit, in two non‐independent but equivalent binding sites. Molecular dynamics studies suggest that end‐stacking of 3 d induces a conformational rearrangement in the G4 structure, driving the binding of a second 3 d ligand to a G4 groove. Modeling studies also suggest that 3 d , with two three‐carbon side chains, has the appropriate geometry to participate in direct or water‐mediated hydrogen bonding to the phosphate backbone and/or G4 loops, assisted by the terminal nitrogen atoms of the side chains. Additionally, antiproliferative studies showed that IQc compounds 2 d (2‐{[3‐(diethylamino)propyl]amino}‐5‐methyl‐11H‐indolo[3,2‐c]quinolin‐5‐ium chloride) and 3 d are 7‐ to 12‐fold more selective for human malignant cell lines than for nonmalignant fibroblasts. 相似文献
A novel and efficient synthesis of 11‐fluoro‐11H‐indeno[1,2‐c]quinolines has been developed via a palladium‐catalyzed three‐component reaction of 2‐alkynylbromobenzenes, 2‐alkynylanilines, and N‐fluorobenzenesulfonimide. The reaction works well with high selectivity. Additionally, the diversity and complexity could be easily introduced via a simple operation from readily available starting materials. In the meantime, a fluorine atom could be incorporated into the scaffold during the reaction process. 相似文献
An efficient and practical copper‐catalyzed domino synthesis of benzo[4,5]imidazo[1,2‐a]pyrimidin‐4(10H)‐ones has been developed. The protocol uses N‐(2‐halophenyl)‐3‐alkylpropiolamides and cyanamide as the starting materials, inexpensive copper(I) iodide and pipecolinic acid as the catalyst and ligand, and the corresponding products were obtained in moderate to good yields.
A convenient gold‐catalyzed strategy for the synthesis of imidazo[1,2‐a]pyridine derivatives has been developed via gold carbene complexes. This transformation opens a new synthetic route to a variety of 3‐carbonyl‐substituted imidazo[1,2‐a]pyridines using air as oxidant affording the products in good yields.
An efficient cascade methodology toward chemoselective synthesis of N‐fused heterocycles including 9H‐pyrrolo[1,2‐a]indole, 3H‐pyrrolo[1,2‐a]indole and 1H‐pyrrolo[1,2‐a]indole derivatives has been developed. This transformation proceeds via a silver(I) triflate‐catalyzed consecutive Friedel–Crafts reaction/N C bond formation sequence between readily available propargyl alcohols and 3‐substituted 1H‐indoles. Not only is excellent chemoselectivity observed according to the substitution patterns of propargyl alcohols, but also the Lewis acid‐catalyzed N C bond formation process can be carried out under base‐ and ligand‐free conditions. 相似文献
17 monodentate phosphepine ligands with a 4,5‐dihydro‐3H‐dinaphtho[2,1‐c;1′,2′‐e]phosphepine structural motif have been synthesized and tested in the asymmetric hydrogenation of various β‐keto esters. By variation of the substituents of the aryl group on the phosphorus atom a fine tuning of the selectivity of the catalytic system is possible. Quantitative yield and enantioselectivities up to 95% ee have been achieved for the hydrogenation of methyl acetoacetate ( 7a ), methyl 3‐oxovalerate ( 7b ) and ethyl 4‐phenyl‐3‐oxo‐propionate ( 7d ) using 4‐(4‐methoxyphenyl)‐4,5‐dihydro‐3H‐dinaphtho‐[2,1‐c;1′,2′‐e]phosphepine ( 4g ) as ligand. Best enantioselectivities were obtained at comparably high temperatures (100–120 °C), which had the advantage of increased reaction rates. 相似文献
A new [3+2] cycloaddition strategy for the direct synthesis of highly substituted pyrroles from the readily available α‐acylketene dithioacetals (or related substrates) and commercially available propargylamines under mild metal‐free conditions has been developed. In this reaction, the acyl group plays a critical role in driving the conjugate addition of propargylamine and further cyclization to give pyrroles. Furthermore, the wide scope was confirmed by the preparation of 1,2,3,4‐tetrasubstituted pyrroles (60–70% yields) via a formal 1,2‐acyl migrating [3+2] cycloaddition pathway with N‐methylprop‐2‐yn‐1‐amine as the secondary amine component. 相似文献