Pyridylethyl: A versatile protecting group. Part II. The protection of heterocyclic N-H groups

Pyrrole, indole, carbazole and imidazole have been protected as N-[2-(4-pyridyl)ethyl] derivatives. Deprotection occurred under mild conditions after quaternisation. 3-Bromoindole was prepared by bromin-ation of the protected parent indole.     

Highly Efficient Synthesis of Thieno[2,3‐b]indole Derivatives

Thieno[2,3‐b]indole derivatives were efficiently prepared via the reaction of 1,3‐dihydro‐2H‐indole‐2‐thiones with α‐bromo‐substituted ketones or aldehydes and in the presence of Et₃N (Scheme 2 and Table). The reaction took place under very mild conditions and in short times with good to excellent yields.     

Synthesis,Characterization, and Screening for Anti‐inflammatory and Antimicrobial Activity of Novel Indolyl Chalcone Derivatives

Because of the great biological importance of substituted indole derivatives, in the present study, a series of pyrazolylindole, thiazolylindole, and pyrimidinylindole derivatives have been synthesized with good yield. The precursor indolyl chalcone 2a – d was prepared by reaction of 3‐chloro‐1H‐indole‐2‐carbaldehyde 1 with different ketones. Then, compounds 3b – d , 4 , and 5a – d have been synthesized by the reaction of chalcones 2a – d with hydrazine, phenylhydrazine, and thiosemicarbazide. When the chalcone derivative 2b subjected to react with hydroxylamine hydrochloride gave isoxazolylindole derivative 6b . N‐thiazolidine pyrazolyl indole 7 was obtained by reacting compound 5a with ethyl chloroacetate. On the other hand, when chalcone derivative 2b allowed to react with urea and thiourea gave the corresponding pyrimidinylindole derivatives 8 and 9 . Finally, when chalcone derivative 2b reacted with ethyl cyanoacetate or malononitrile gave pyridinylindole derivatives 10 and 11 . The structures of the all synthesized compounds were elucidated on the basis of spectral analysis infrared, NMR, and mass spectroscopy. Some of the synthesized compounds were screened for their antimicrobial and anti‐inflammatory activity. Compound 4b was the highest antibacterial activity against all strains of bacteria with values higher than those of the corresponding reference antibiotics (ciprofloxacin and levofoxacin, respectively) and almost the same as (gemifloxacin, moxifloxacin, clindamycin, gentamycin, and streptomycin). Compounds 4 , 5 , 6 , and 7 showed high anti‐inflammatory activity compared with the standard drug indomethacin.     

Synthesis and Antibacterial Activity of Some Substituted 3-(Aryl)- and 3-(Heteroaryl)indoles

Summary. A synthesis of 3-(4-methoxycarbonyl-2,6-dinitrophenyl)indole, its 2,6-diamino analog, and 3-(2-amino-4-trifluoromethyl-6-nitrophenyl)indole is described. 4-(Trifluoromethyl)phenyl derivatives exhibit higher antibacterial potency than the former 4-(methoxycarbonyl)phenyl homologs, while 3-(4-trifluoromethyl-2-nitrophenyl)indole was the most active agent in the series, with MIC ≈ 7 μg/cm³ against E. coli and S. aureus.     

A Convenient and Efficient Route to 1,4-Bis（heteroaryl）-buta-1,3-diene and 4-Heteroarylbut-1-en-3-yne from 1,4-Dichlorobut-2-yne

A convenient and practical route to functionalized conjugated 1,3-enynes and 1,3-dienes is described. 1,4-Bis（heteroaryl）- 1,3-diene and 1-heteroarylbut- 1-en-3-yne derivatives were prepared from 1,4-dichloro-2-butyne and corresponding N-heteroarenes such as imidazole, pyrrole, pyrazole and indole derivatives in the presence of bases in good to high yields.     

An Efficient Ugi‐Azide Four‐Component Approach for the Preparation of Novel 1‐(1H‐tetrazol‐5‐yl)‐10‐chloro‐1,2,3,4‐tetrahydropyrazino[1,2‐a] Indoles

The synthesis of novel 1‐(1H‐tetrazol‐5‐yl)‐10‐chloro‐1,2,3,4‐tetrahydropyrazino[1,2‐a] indole derivatives starting from the initially prepared 1‐(2‐bromoethyl)‐3‐chloro‐1H‐indole‐2‐carbaldehyde is described. A variety of likely biologically relevant pyrazino[1,2‐a] indole‐based 1,5‐disubstituted tetrazoles was obtained in moderate to high yields via an Ugi‐azide reaction. These reactions presumably proceed by the imine formation, intramolecular cyclization to iminium ion, and nucleophilic addition tandem reactions, respectively.     

Synthesis of symmetrical and unsymmetrical diindolylmethanes via acid-catalysed electrophilic substitution reactions

A range of activated indole-2-carboxylate derivatives was prepared via the Hemetsberger indole synthesis. Vilsmeier formylation was explored to establish regioselectivity and to prepare a range of new indole carbaldehydes. The indole aldehydes were reduced to the corresponding hydroxymethylindoles in good yields by the use of sodium borohydride in THF. Symmetrical 4,4′-, 6,6′- and 7,7′-diindolylmethanes were prepared via the acid-catalysed reaction of the corresponding hydroxymethylindoles. Furthermore, the treatment of methyl 4-hydroxymethyl-5,6-dimethoxyindole-2-carboxylate and a range of methyl indole esters with acetic acid led to the formation of unsymmetrical 4,6′- and 4,7′-dindolylmethanes.     

Synthesis,Reactions and Antimicrobial Activity of Some New Indolyl‐1,3,4‐Oxadiazole,Triazole and Pyrazole Derivatives

Indole‐3‐carboxylic acid hydrazide 3 was prepared and was treated with aromatic aldehydes in ethanol to give the corresponding hydrazone derivatives 4–7 in good yields. The indole carbohydrazide was incorporated into the 3‐indolyloxadiazoles 8–11 and 18 , 3‐indolyltriazoles 13–17 and 35 , 3‐indolylpyrazole derivatives 19–23 and carbamate derivatives 26–27 . Furthermore, interaction of the carboazide 24 with hydrazine hydrate in refluxing toluene afforded the corresponding semicarbazide derivative 30 . The thiadiazine derivative 34 was also prepared. Some of these compounds were screened in vitro for their antibacterial and antifungal activity.     

Synthesis of New PMB‐Substituted Indoles Containing 1,3,4‐Oxadiazole and 1,2,4‐Triazole Units

A series of new indolyl‐1,3,4‐oxadiazole derivatives 3 , 4 , 5 , 6 , 7 and 10 , indolyl‐1,2,4‐triazole derivatives 14 and 15 was prepared, using 1‐(4‐methoxybenzyl)‐1H‐indole‐3‐carbohydrazide ( 2 ) as a key intermediate. Some of the new compounds were evaluated for their antineoplastic activity.     

The reaction of indole and the indole grignard reagent with phosgene. A facile synthesis of indole-3-carboxylic acid derivatives

Indole-3-carboxylic acid (as well as indole-3-glyoxylic acid) derivatives are readily prepared from indoles (including oxindoles) and phosgene (oxalyl chloride), respectively. The interaction of these reagents with the indole Grignard reagent afforded several products including the cyclo-tetramers, 21 and 30 . Indolo-fused heterocycles can be readily prepared from the reaction of phosgene (or oxalyl chloride) with suitable reactants. Thus e.g., phosgene and 2-(2-hydroxy-phenyl)-N-methylindole readily gave 5,6-dihydro-11-methyl-6-oxobenzo[a]pyrano[4,3-b] indole ( 33 ).     

Complexation of Indole-3-acetic Acid with Iron(III): Influence of Coordination on the π-Electronic System of the Ligand

Summary.  The iron(III) complex of indole-3-acetic acid (1) was prepared, and its physicochemical properties, mode of iron(III) coordination, and electronic structure were studied using UV/Vis, diffuse reflectance infrared Fourier transform (DRIFT), and transmission ⁵⁷Fe M?ssbauer spectroscopic techniques. The data obtained provide evidence that iron(III) is not only coordinated by the carboxylic O-donor atom, but also via the conjugated π-electronic system of the pyrrole moiety involving both the non-shared electronic pair of the heteroatom and the C(2)*C(3) double bond. Considering the well-known increased sensitivity of the pyrrole residue in indole derivatives to oxidation as compared to the benzene ring, as well as the formation of a triple complex (peroxidase-1-O₂) proposed for the enzymatic 1 oxidative degradation mechanism involving as a key step the Fe³⁺ → Fe²⁺ transition in the enzyme form as discussed in literature, it is concluded that iron(III) coordination with 1 can influence the redox properties of the pyrrole ring by affecting its π-electronic system. Received September 17, 2000. Accepted (revised) October 31, 2000     

Synthesis and properties of [1,4]diazepino[6,5-b]indoles

1-Aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxides were synthesized based on 3-(N"-aryl-N"-chloroacetyl)amino-2-formylindoles. Deoxidation of 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxide afforded 1,2,3,6-tetrahydro- and 1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole derivatives. A new approach to the synthesis of pyrido[3,2-b]indole and pyrimido[5,4-b]indole derivatives was developed.     

New synthesis of condensed hydropyridazine derivatives. VI

The reactivity of some indole derivatives towards the semicarbazone of ω-bromoacetophenone has been reported. Substituents at position 1 and 2 of the indole ring greatly affect the course of the reaction. 1,4,4a,9a-Tetrahydro-9H-pyridazino[3,4-b]indole derivatives or 3-indolyl derivatives were obtained depending on the substituents. The structures were assigned on the basis of satisfactory analytical and spectroscopic data.     

Substituted Pyrrolo[3,4-<Emphasis Type="Italic">a</Emphasis>]carbazoles from Reactions between 3-(1-Methoxy-vinyl)indoles and Maleimides

Summary. 5-Methylenolether derivatives of pyrrolo[3,4-a]carbazoles were obtained from cycloadditions between 3-(1-methoxyvinyl)-1-tosylindole and N-substituted maleimides. They were transformed into the hydroxy derivatives by treatment with H₂SO₄, selectively reduced to the ether by H₂/Pd–C, and in the imide moiety by L-Selectride^?. From the analogous BOC protected indole derivative the parent α,β-unsaturated ketones were obtained, which were transformed into hydroxyimino compounds, and which could be deprotected by heating to the melting point. Deprotection of the tosyl derivatives was not successful. The imide part of the molecule was hydrolyzed using methanolic NaOH. The stereochemistry of all products was elucidated mainly by spectroscopic methods, and compared with results of calculations.     

Cyclization reactions of 3-hydrazino[1, 2, 4]triazino[5, 6-b]indole

The reaction of 3-hydrazino[1, 2, 4]triazino[5, 6-b]indole I with nitrous acid affords the azide III which could be cyclized with acetic anhydride to 10-acetyl-10H-tetrazolo[5′,1′:3, 4][1, 2, 4]triazino[5, 6-b]indole IIb . Cyclization reactions of I with acetic anhydride, ethyl chloroformate, carbon disulphide and aromatic aldehydes to the corresponding fused triazolo derivatives V–VIII are reported. On the other hand cyclization reactions of I with malononitrile, ethyl cyanoacetate, ethyl acetoacetate and acetylacetone to the corresponding condensed pyrazolino derivatives IX–XI are also reported. The reaction of I with α-dicarbonyl compounds to form mono and dihydrazones are reported. The structure of the compounds prepared and their cyclization mechanisms are reported.     

高效液相色谱手性固定相法直接拆分4种吲哚类衍生物

将纤维素-三(3,5-二甲基苯基氨基甲酸酯)(CDMPC)涂敷于自制的球形氨丙基硅胶上,制备成了纤维素-三(3,5-二甲基苯基氨基甲酸酯)手性固定相(CDMPC-CSP)。利用正相高效液相色谱,在该固定相上对新合成的4种吲哚类衍生物对映体进行了手性拆分。通过选择不同结构和浓度的醇类改性剂,优化了色谱分离条件,同时探讨了醇的结构和浓度对于对映体拆分和保留的影响。结果表明,适合Ⅱ~Ⅳ号样品拆分的醇类改性剂分别为正丁醇、乙醇和乙醇,而适合Ⅰ号样品的醇类改性剂为乙醇和正丙醇组成的混合体系。在优化的各流动相体系下,4种吲哚类衍生物的对映体都得到了很好的分离。在此基础上计算了它们的对映体过量值(e.e.值)。实验结果令人满意,表明高效液相色谱手性固定相法是拆分这类化合物的一种理想方法。     

Synthetic studies of decursivine derivatives: preparation of key indole alkaloids via α-hydroxyalkylation

2-Hydroxyacetyl indole modified at C-3 position was prepared with an eye to developing a total synthesis of decursivine derivatives (decursivine, serotobenine, moschaminindolol, and flavumindole). The indole was prepared through a sequence of oxalyl chloride introduction at C-3 position of indole and acid chloride reduction with tributyltin hydride. In addition, we report a novel synthesis of fully functionalized Uhle's ketone via ortho-selective α-hydroxyalkylation.     

Synthesis of 6,7-dihydrobenzo[4,5]cyclohept-[1,2-b]indol-12(5H)-one and related compounds

The synthetic routes of 6,7-dihydrobenzo[4,5]cyclohept[1,2-b]indol-12(5H)-one 5 from either 1-methyl or 1-sulfonylindole-2-carboxaldehyde 1 or ethyl 1,2-dimethylindole-3-carboxylate 6 are reported. The structure of the ketone 5a was confirmed by X-ray crystallography. Several indole derivatives have been prepared with potential antitumor activity.     

Synthesis of 2‐amino‐4h‐thiazolo[5,4‐b]indole and characterization of its colored conversion products with protein tyrosine phosphatase inhibitory activity

In DMSO‐solution 2‐amino‐4H‐thiazolo[5,4‐b]indole is converted into a complex mixture of colored products. The three major conversion end‐products, of which two are inhibitors of protein tyrosine phos‐phatases (PTPs), were isolated by chromatographic methods and their structures characterized by spectro‐scopic analysis, including NMR and MS combined with computer assisted structure elucidation, and, finally, confirmed by independent chemical synthesis. Synthesis of 2‐amino‐4H‐thiazolo[5,4‐b]indole as well as its N‐acetyl derivatives prepared from either oxindole or 2‐bromo‐1‐(2‐nitro‐phenyl)ethanone is described.     

Pyrrolocoumarin derivatives as potential photoreagents toward DNA

A number of new methyl derivatives of linear and angular pyrrolocoumarins were synthesized by direct Fischer's indole synthesis. In the same way some linear 2H,10H-pyrano[2,3-b]carbazol-2-one and angular 2H,7H-pyrano[3,2-c]carbazol-2-one were prepared. The synthesis was performed starting from the 4-methyl-7-aminocoumarin and methyl groups were introduced into positions which look most promising for the photoreactivity of the compounds toward DNA.