Efficient synthesis of N-prenylpyrroloindoline and N-prenylindole alkaloids based on a new four-reaction anionic domino process

Treatment of 2,5-diketopiperazines or carbamates derived from tryptophan or tryptamine with iodomethyltrimethylsilane followed by lithium hexamethyldisilazane and a prenyl halide produced stereoselectively derivatives of the hexahydropyrrolo[2,3-b]indole system bearing prenyl substituents both at C-3a and at the indoline nitrogen in a one-pot procedure involving a novel four-reaction anionic domino process. The reaction was applied to the preparation of N-prenyltryprostatin B and to achieving a very efficient formal total synthesis of the biologically active marine natural product (+/-)-debromoflustramine B.     

单萜吲哚生物碱Uleine及其衍生物的合成进展

生物碱uleine及其衍生物从结构上看属于单萜吲哚生物碱,它们共同的结构特征是吲哚核与碱性氮原子之间只有一个碳相隔,而不像其它单萜吲哚生物碱有两个碳原子.由于其结构特异,天然含量少,因而其合成工作一直吸引着化学工作者.总结uleine生物碱及其衍生物的合成方法,根据构建环的种类不同,把合成方法分为五类.大部分方法都是以吲哚和吡啶衍生物为起始原料进行四环的合成,有几条合成路线简短易行.     

One-pot three-component coupling reaction: solvent-free synthesis of novel 3-substituted indoles catalyzed by PMA-SiO2

Solvent-free PMA-SiO₂-catalyzed synthesis of 3-substituted indole derivatives by a one-pot three-component coupling reaction between aldehyde, N-methyl aniline and indole is described.     

A mild and efficient route to 2-benzyl tryptamine derivatives via ring-opening of β-carbolines

We described a mild and easy method, in two steps, by which various benzyl groups were introduced in the C-2 position of tryptamine. The first step consisted on the synthesis of β-carbolines, starting from tryptamine derivatives, by a Pictet-Spengler reaction. Ring-opening of the β-carbolines, by hydrogenation, led to the desired 2-substituted benzyl tryptamine indole products. A supplementary step of alkylation could be realized to give N-alkyl-2-substituted benzyl tryptamine. During these reactions, nitrogen atoms require no step of protection.     

TiCl4/Et3N-promoted three-component condensation between aromatic heterocycles, aldehydes, and active methylene compounds

A one-pot methodology for the synthesis of polyfunctionalized indole derivatives by a TiCl4/Et3N-promoted trimolecular condensation of aldehydes, indole heterocycles, and various activated carbonyl compounds is reported. Rationalization of these reactions and extension to other heterocyclic systems is also described.     

Fluorinated N-[2-(haloalkyl)phenyl]imidoyl chloride, a key intermediate for the synthesis of 2-fluoroalkyl substituted indole derivatives via Grignard cyclization process

Fluorinated N-[2-(haloalkyl)phenyl]imidoyl chloride, which was readily available from the corresponding anilines by using Uneyama's one-pot synthesis of fluorinated imidoyl chloride, was found to be a key intermediate for the facile synthesis of 2-fluoroalkyl substituted indole derivatives via the Grignard cyclization process. The bromination of 3-methyl group of 3-methyl-2-trifluoromethyl indole with NBS/CCl₄ led to the formation of 3-bromomethyl substituted indole which can be further utilized to synthesize some new and biologically interested indole derivatives.     

p-TsOH promoted Fischer indole synthesis of multi-substituted 2-trifluoromethyl indole derivatives

A p-TsOH promoted one-pot synthesis of multi-substituted 2-trifluoromethyl indole derivatives, for instance, 2-trifluoromethyl-3-phenylindoles, 2-trifluoromethyl-indole-3-propanoates, and 2-trifluoromethyl-indole-3-butanoates from reactions of 1,1,1-trifluoro-3-phenylacetone and simply prepared ω-trifluoromethyl substituted δ and ?-ketoesters with arylhydrazines via Fischer indole synthesis has been developed.     

Sequential one-pot five-component synthesis of tetrazole-based spirotetrahydro-β-carbolines

A one-pot five-component two-step sequential synthesis of tetrazole-based tetrahydrospiro[indene-2,1′-pyrido[3,4-b]indole]-1,3-diones in moderate to good yields is described. The reaction consists of four-component condensation of aromatic aldehydes with tryptamine, trimethylsilyl azide (TMSN₃) and isocyanides, followed by addition of ninhydrin. These reactions presumably proceeded through Ugi-azide/Pictet–Spengler processes, respectively.     

Direct Synthesis of Structurally Divergent Indole Alkaloids from Simple Chemicals

A direct and structurally divergent synthesis of indole alkaloids from very simple 2‐vinylanilines, alkynes and TBN via a novel substrate fragmentation/cycloaddition strategy has been developed, which provides an efficient noble‐metal‐free approach to access a library of highly valuable indole derivatives of tryptamines and tryptamine‐related oximes, lactams, and lactones, as well as β‐carbolines, spiroindolines, and hexa‐hydropyrrolo[2,3‐b]indoles.     

Synthesis of Indole Derivatives Attached to Polyethylene Oxides)

N-Benzyl 5-, 6-, and 7-bromoindolines were converted to the respective organosodium derivatives and used as initiators for the anionic polymerization of ethylene oxide. The resulting indoline derivatives attached to polyethylene oxide were dehydrogenated to the indole derivatives, which in turn were converted through suitable reactions to the tryptamine and indole acetic acid derivatives.     

Synthesis of tryptamine derivatives via a direct, one-pot reductive alkylation of indoles

An efficient, one-pot reductive alkylation of indoles with N-protected aminoethyl acetals in the presence of TES/TFA is reported. It represents the first general method for the direct synthesis of tryptamine derivatives from indoles and nitrogen-functionalized acetals. This convergent and versatile approach employs safe and inexpensive reagents, proceeds under mild conditions, and tolerates several functional groups. The new procedure was efficiently applied to a gram-scale synthesis of both luzindole, a reference MT2-selective melatonin receptor antagonist, and melatonin.     

Palladium-catalyzed synthesis of indole fused coumarins via cross-dehydrogenative coupling

The present method describes a palladium-catalyzed cross-dehydrogenative coupling reaction of coumarin and aniline for the synthesis of indole fused coumarin derivatives. The one-pot method is operationally simple and molecular oxygen is used as sole oxidant. The target compounds are obtained in good yields from commercially available precursors.     

Efficient one-pot synthesis of tryptamines and tryptamine homologues by amination of chloroalkynes

A new method was developed for the one-pot synthesis of substituted 3-(2-aminoethyl)- and 3-(3-aminopropyl)indoles from commercially available aryl hydrazines and chloroalkylalkynes. Various tryptamine derivatives were prepared directly in good yield with excellent regioselectivity. The method involves a new domino reaction sequence consisting of a titanium-catalyzed amination of the chloroalkylalkyne, [3+3]-rearrangement of the resulting aryl hydrazone, and nucleophilic substitution of the chloride by ammonia.     

A direct access to 3-(2-Oxoalkyl)indoles via aluminum chloride induced C-C bond formation

3-Methylindole is acylated regioselectively at the methyl group when treated with a variety of acyl chlorides in 1,2-dichloroethane in the presence of AlCl(3), affording a mild and direct method for the synthesis of 3-(2-oxoalkyl)indoles. The product formation in this one-pot reaction largely depends on the conditions of the reaction employed. The methodology does not require protection-deprotection steps and is amenable for the scale-up synthesis of these indole derivatives.     

A novel one-pot four-component access to tetrahydro-beta-carbolines by a coupling-amination-aza-annulation-Pictet-Spengler sequence (CAAPS)

The four-component coupling-amination-aza-annulation-Pictet-Spengler (CAAPS) sequence of acid chlorides 1, terminal alkynes 2, tryptamine derivatives 6, and acryloyl chloride derivatives 4 represents a facile and rapid one-pot access to tetrahydro-beta-carbolines 7 in moderate to good yields.     

A general synthesis of substituted indoles from cyclic enol ethers and enol lactones

[reaction: see text] X = CH2, C[double bond]O, R2 = H, alkyl. A general method was developed for the one-pot synthesis of highly functionalized indoles from simple, commercially available aryl hydrazines and cyclic enol ethers. Enol lactones were also used as substrates, affording substituted indole acetic acid or indole propionic acid derivatives. This procedure affords 2,3-disubstituted indoles as single regioisomers from the appropriately substituted enol ether or enol lactone. This method was highlighted in the efficient synthesis of the antimigraine drug sumitriptan and the antiinflammatory drug indomethacin.     

Synthesis of Poly-5-vinylindole Derivatives

5-Vinyl-N-benzylindoline and 5-vinyl-N-benzylindole were synthesized starting from the corresponding 5-formyl derivative, by utilizing the Wittig or Wittig-Horner reactions. The monomers were polymerized by free-radical (AIBN) and anionic (BuLi) catalysts. Poly-5-vinyl-N-benzylindole was converted through suitable reactions to the tryptamine and indole acetic acid derivatives. Poly-5-vinyl-N-benzyl-tryptophane was synthesized by malonic ester synthesis by utilizing the condensation of poly-5-vinyl-N-benzylgramine and diethyl formamidomalonate.     

Unexpected formation of fluorine-containing tetrahydrocarbazole during the reaction of indole, paraformaldehyde, and fluorine-containing β-ketoesters

A surprise and mild method to prepare fluorine-containing indole derivatives through a one-pot three-component condensation reaction sequence is presented. To our surprise, during the reaction of preparation of fluorine-containing indole derivatives, unexpected formation of fluorine-containing tetrahydrocarbazole was found. Moreover, this method has been demonstrated in the preparation of functionalized polycyclic indole derivatives in a straightforward and atom-economical manner.     

Synthesis of functionalized indole- and benzo-fused heterocyclic derivatives through anionic benzyne cyclization

The development of a new method for the regioselective synthesis of functionalized indoles and six-membered benzo-fused N-, O-, and S-heterocycles is reported. The key step involves the generation of a benzyne-tethered vinyl or aryllithium compound that undergoes a subsequent intramolecular anionic cyclization. Reaction of the organolithium intermediates with selected electrophiles allows the preparation of a wide variety of indole, tetrahydrocarbazole, dihydrofenantridine, dibenzopyran, and dibenzothiopyran derivatives. Finally, the application of this strategy to the appropriate starting materials allows the preparation of some tryptamine and serotonin analogues.     

“On-water” synthesis of 3-substituted indoles via Knoevenagel/Michael addition sequence catalyzed by Cu doped ZnS NPs

Cu doped ZnS NPs represent a green catalyst for an ‘on-water’ one-pot rapid synthesis of 3-substituted indole derivatives via Knoevenagel/Michael addition reaction of indane-1,3-dione, aromatic aldehydes, and indole. The catalytic activity of Cu doped ZnS NPs was about sevenfold higher as compared to the ZnS NPs. The Cu doped ZnS NPs catalyst could be recovered and reused for five reaction cycles, giving a total TOF = 201 h⁻¹.