PEG-SO3H as a Catalyst for the Preparation of Bis-Indolyl and Tris-Indolyl Methanes in Aqueous Media

A facile, efficient, and green synthesis of bis-indolyl and tris-indolyl methanes has been developed by one-pot condensation of indole with structurally diverse aldehydes and ketones in the presence of poly(ethylene glycol)–bound sulfonic acid as catalyst at room temperature.     

PEG-600: a facile and eco-friendly reaction medium for the synthesis of N-alkyl derivatives of indole-3-carboxyaldehyde

Abstract

A facile and eco-friendly methodology for the synthesis of N-alkyl/aralkyl derivatives of indole & indole-3-carboxyaldehydes mediated by polyethylene glycol as an efficient and green solvent is described.     

π–π Stacking Interaction in an Oxidized CuII–Salen Complex with a Side-Chain Indole Ring: An Approach to the Function of the Tryptophan in the Active Site of Galactose Oxidase

In order to gain new insights into the effect of the π–π stacking interaction of the indole ring with the Cu^II–phenoxyl radical as seen in the active form of galactose oxidase, we have prepared a Cu^II complex of a methoxy-substituted salen-type ligand, containing a pendent indole ring on the dinitrogen chelate backbone, and characterized its one-electron-oxidized forms. The X-ray crystal structures of the oxidized Cu^II complex exhibited the π–π stacking interaction of the indole ring mainly with one of the two phenolate moieties. The phenolate moiety in close contact with the indole moiety showed the characteristic phenoxyl radical structural features, indicating that the indole ring favors the π–π stacking interaction with the phenoxyl radical. The UV/Vis/NIR spectra of the oxidized Cu^II complex with the pendent indole ring was significantly different from those of the complex without the side-chain indole ring, and the absorption and CD spectra exhibited a solvent dependence, which is in line with the phenoxyl radical–indole stacking interaction in solution. The other physicochemical results and theoretical calculations strongly support that the indole ring, as an electron donor, stabilizes the phenoxyl radical by the π–π stacking interaction.     

Rapid access to the Welwitindolinone alkaloid skeleton by cyclization of indolecarboxaldehyde substituted cyclohexanones

[reaction: see text] A very rapid access to cyclohexanone-bridged indole systems was established by an acid-mediated ring closure of appropriately substituted indole aldehydes, which involved an apparent disproportionation of an aldol-like intermediate. One of the bridged indole intermediates was further transformed into an oxindole having the essential skeleton of the Welwitindolinone alkaloids.     

吲哚的直接气相合成: MgO助剂对Cu/SiO2催化剂性能的影响

将MgO作为助剂用于苯胺和乙二醇直接气相合成吲哚Cu/SiO2催化剂中,通过X射线衍射、程序升温还原和热重分析对催化剂进行了表征.结果表明,适量(如0.17mmol/g)MgO的添加不仅提高了催化剂的活性,而且显著增强了催化剂的稳定性.加入的MgO可与CuO发生一定的相互作用,从而改善铜在二氧化硅表面上的分散,抑制铜在反应过程中的烧结.此外,MgO还减少了催化剂的积炭.     

ZnO对Ag/SiO2催化剂银的分散作用及对吲哚合成稳定性的影响

将ZnO助剂加到由苯胺和乙二醇一步合成吲哚的Ag/SiO2催化剂中,发现ZnO助剂能大大提高催化剂的稳定性.XRD和TEM表征首次得到:ZnO是结构型助剂,它能使银很好地分散在SiO2表面上,并可有效地抑制反应过程中银粒子的烧结.     

Carbohydrate recognition at the minor-groove of the self-complementary duplex d(CGCGAATTCGCG)2 by a synthetic glyco-oligoamide

The structure of a neutral glyco-conjugate β-Gal-Py-γ-Py-Ind (1), designed as a probe for analyzing sugar-DNA interactions, when bound to a self-complementary oligonucleotide duplex d(CGCG AATT CGCG)(2) has been deduced by employing (1)H NMR techniques. Analysis of the formed 1:1 complex demonstrated that the glycol ligand is bound in a hairpin-like conformation in which both pyrrole amino acid moieties are stacked, whereas the indole and the sugar residues are spatially close. The binding site is defined by the minor groove formed by the -AATT- stretch. In particular, the -Py-γ-Py- region of the ligand is sited near the A5-A6 oligonucleotide residues, whereas the indole and the sugar rings are next to the T7-T8 base pairs. More relevant, the existence of a variety of intermolecular NOE correlations permitted the close proximity of the sugar to the minor groove to be assessed, thus showing that the binding of the glycoconjugate at the minor groove is the origin of the specificity of the glycoconjugate-DNA interaction. The experimental NMR data have been combined with restrained and unrestrained molecular dynamics calculations, to provide the 3D structure of the complex.     

An unusual hydrogen addition of indolo-2,3-quinodimethanes to dimethylindoles in the presence of 1,3-azoles

Indolo-2,3-quinodimethane generatedin situ frombis-(bromomethyl)indole with NaI/DMF at 70°C was expected to undergo cycloaddition with 1,3-azoles to give carboline derivatives, which form the backbone of many indole alkaloids. However, the reaction did not give the anticipated product but proceeded via hydrogen addition to exocyclic methylene groups, furnishing dimethylindoles in good yields     

Electrostatic contributions to indole-lipid interactions

The role of electrostatic forces in indole-lipid interactions was studied by (1)H and (2)H NMR in ether- and ester-linked phospholipid bilayers with incorporated indole. Indole-ring-current-induced (1)H NMR chemical shifts of lipid resonances in bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-di-O-octadecenyl-sn-glycero-3-phosphocholine, and 1,2-di-O-octadecenyl-sn-glycero-3-phosphomethanol show a bimodal indole distribution, with indole residing at the upper hydrocarbon chain/glycerol region of the lipid and near the choline group, when present. (2)H NMR of indole-d(7)-incorporated lipid bilayers reveals that the former site is occupied by about two-thirds of the indole, which adopts a distinct preferred orientation with respect to the bilayer normal. The results suggest that the upper hydrocarbon chain/glycerol location is dictated by many factors, including interactions with the electric charges and dipoles, van der Waals interactions, entropic contributions, and hydrogen bonding. Indole diffusion rates are higher in lipids with ester bonds and lower in choline-containing lipids, suggesting that interactions between indole and carbonyl groups are of minor importance for lipid-indole association and that cation-pi interactions with choline drive the second indole location. Nuclear Overhauser effect spectroscopy cross-relaxation rates suggest a 30-ns lifetime for indole-lipid associations. These results may have important implications for sidedness and structural transitions in tryptophan-rich membrane proteins.     

Nucleophilic substitution and cyclization reactions involving quaternized 3-dimethylaminomethyl derivatives of 3,4-bis(indol-l-yl)maleimide and 3-(indol-l-yl)-4-(indolin-l-yl)maleimide

A dialkylaminomethylation reaction (the Mannich reaction) of 3,4-bis(indol-l-yl)-maleimides and 3-(indol-l-yl)-4-(indolin-l-yl)maleimides leads to mono- and di(dimethyl-amino) derivatives at position 3 of one or two indole rings. A series of 3,4-bis(indol-l-yl)-maleimides and 3-(indol-l-yl)-4-(indolin-l-yl)maleimides containing ω-hydroxyalkyloxy-methyl substituents at position 3 of the indole ring was obtained by the reaction of iodomethyl-ates of these compounds with ethylene glycol and other 6h,ω-alkanediols. The reaction of quaternary salts of bis(3-dimethylaminomethylindol-l-yl)maleimides with 6h,ω-alkanediols resulted in the isolation of 3,4-bis(3-ω-hydroxyalkyloxymethylindol-l-yl)maleimides. Upon heating iodomethylate of 3-(3-dimethylaminoindol-l-yl)-4-(indolin-l-yl)maleimide in pyridine, 5,6-dihydro-10-methyl-H-indolo[l′,7a′,7′:4,5,6]pyrrolo[3′,4′:2,3]-[l,4]diazepino[l,7-a]-indole-l,3(2H)-dione was obtained due to the intramolecular alkylation and formation of the bond between position 2 of the indole and position 7 of the indoline rings.     

Indole-tolerant Oxidation of 1,2-Diarylalkynes to 1,2-Diketone Derivatives

A new indole-tolerant oxidation condition for the synthesis of 1,2-diketone derivatives from the corresponding 1,2-diarylalkynes was described. By screening a series of oxidation systems on alkynes linked with indole and different substituted aromatic ring, the DMSO/PdCl₂/CuCl₂ system afforded moderate to good yields despite the existence of electron-rich indole ring.     

苯胺和乙二醇生成吲哚反应机理的DFT理论研究

利用传统过渡态理论研究了苯胺和乙二醇生成吲哚反应的机理,设计了四种可能的反应通道.优化计算了反应物、产物和每个通道中可能的中间体和过渡态的几何构型,找出并确认了每个反应通道中各基元反应的可能过渡态和活化能.经分析对比给出该反应可能的主反应通道.同时初步探讨了在经过渡态TS1的基元反应中加入催化剂Ag后的反应机理.加入催化剂后,反应的活化能降低.     

Biotransformation of Indole to Indigo by the Whole Cells of Phenol Hydroxylase Engineered Strain in Biphasic Systems

Biotransformation of indole to indigo in liquid–liquid biphasic systems was performed in Escherichia coli cells expressing phenol hydroxylase. It was suggested that indole could inhibit the cell growth even at low concentration of 0.1 g/L. The critical Log P for strain PH__IND was about 5.0. Three different solvents, i.e., decane, dodecane, and dioctyl phthalate, were selected as organic phase in biphasic media. The results showed that dodecane gave the highest yield of indigo (176.4 mg/L), which was more than that of single phase (90.5 mg/L). The optimal conditions for biotransformation evaluated by response surface methodology were as follows: 540.26 mg/L of indole concentration, 42.27 % of organic phase ratio, and 200 r/min of stirrer speed; under these conditions, the maximal production of indigo was 243.51 mg/L. This study proved that the potential application of strain PH__IND in the biotransformation of indole to indigo using liquid–liquid biphasic systems.     

Synthesis of the cycloheptannelated indole fragment of dragmacidin E

Synthesis of the pivotal cycloheptannelated indole fragment of indole alkaloid dragmacidin E is achieved. The synthesis features a Pd-catalyzed indole synthesis reaction for the preparation of 3,7-disubstituted indole, a regioselective intramolecular Friedel–Crafts reaction for the construction of the 3,4-bridged cycloheptannelated indole skeleton, and a coupling reaction of vinyl triflate with diorganocuprate.     

A directed metalation route to the zwitterionic indole alkaloids. : Synthesis of sempervirine

A synyhesis protocol involving beta-lithiation of 2-(2-pyridinyl)indoles (4 → 5) and subsequent reaction with bromoacetaldehyde leads to the indol[2,3-a]quinolzine(1)ring system. Application of this methodology to 2-(2-pyridinyl)indole 17, which is prepered via Taylor-Boger triazine Dieis-Alder annulation chemistry, affords the zwitterionic indole alkaloid sempervirine (3).     

Direct approaches to annulated indoles. A formal total synthesis of 0231B

An advanced intermediate in the Nakatsuka synthesis of 0231B was prepared using a fluoride-mediated indole formation in the key step. Both palladium-based approaches and hydride-based approaches failed to generate the indole.     

The novel approach to indole alkaloids by using Pd(II)-catalyzed cyclization

The synthesis of indole skeleton by using Pd(II)-catalyzed cyclization of the urethane has been achieved. The urethanes with allylic alcohol were converted into vinyl indolines in good yield. The vinyl indoline was transformed into some intermediates of indole alkaloids.     

Oxidation reactions of indapamide. A novel route to the indole derivative,N-(3-sulfamyl-4-chlorobenzamido)-2-methylindole

Indapamide ( 1 ) is readily oxidized with mild oxidizing agents to the indole derivative 2 . Dehydrogenation of indapamide is a convenient one step synthesis of a complex indole compound.     

A pyrone remodeling strategy to access diverse heterocycles: application to the synthesis of fascaplysin natural products

The synthesis of diverse N-fused heterocycles, including the pyrido[1,2-a]indole scaffold, using an efficient pyrone remodeling strategy is described. The pyrido[1,2-a]indole core was demonstrated to be a versatile scaffold that can be site-selectively functionalized. The utility of this novel annulation strategy was showcased in a concise formal synthesis of three fascaplysin congeners.

The synthesis of diverse N-fused heterocycles, including the pyrido[1,2-a]indole scaffold, using an efficient pyrone remodeling strategy is described.     

The diazo route to diazonamide A. Studies on the indole bis-oxazole fragment

[structure: see text] Various approaches to the indole bis-oxazole fragment of the marine secondary metabolite diazonamide A are described, all of which feature dirhodium(II)-catalyzed reactions of diazocarbonyl compounds in key steps. Thus, 3-bromophenylacetaldehyde is converted into an alpha-diazo-beta-ketoester, dirhodium(II)-catalyzed reaction of which with N-Boc-valinamide resulted in N-H insertion of the intermediate rhodium carbene to give a ketoamide that readily underwent cyclodehydration to give (S)-2-(1-tert-butoxycarbonylamino)-2-methylpropyl]-5-(3-bromobenzyl)oxazole-4-carboxamide, after ammonolysis of the initially formed ester. This aryl bromide was then coupled to a 3-formyl-indole-4-boronate under Pd catalysis to give the expected biaryl. Subsequent conversion of the aldehyde group into a second alpha-diazo-beta-ketoester gave a substrate for an intramolecular carbene N-H insertion, although attempts to effect this cyclization were unsuccessful. A second approach to an indole bis-oxazole involved an intermolecular rhodium carbene N-H insertion, followed by oxazole formation to give (S)-2-[1-tert-(butoxycarbonylamino)-2-methylpropyl]-5-methyloxazole-4-carboxamide. A further N-H insertion of this carboxmide with the rhodium carbene derived from ethyl 2-diazo-3-[1-(2-nitrobenzenesulfonyl)indol-3-yl]-3-oxopropanoate gave a ketoamide, cyclodehydration of which gave the desired indole bis-oxazole. Finally, the boronate formed from 4-bromotryptamine was coupled to another diazocarbonyl-derived oxazole to give the corresponding biaryl, deprotection and cyclization of which produced a macrocyclic indole-oxazole derivative. Subsequent oxidation and cyclodehydration incorporated the second oxazole and gave the macrocyclic indole bis-oxazole.