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Indoloquinoline alkaloids constitute an important class of aromatic heterocycles consisting of quinoline and indole fused together in various orientations. These compounds, both natural and synthetic, often display various bioactivities which have established them to be one of the interesting medicinal targets. This class of compounds have stimulated much interest among synthetic and medicinal chemists as evidenced by growth in the number of synthetic methods to prepare and study this class of alkaloids. This review compiles the synthetic strategies and methods currently known in the literature for the construction of four important indoloquinoline skeletons.

ortho-Alkynylarylketone derivatives were employed as key precursors for a one-pot synthesis of arylnaphthalenelactone and furanonaphthol libraries. In this work, we discovered a cost-effective protocol to prepare arylnaphthalenelactones in one-pot using inexpensive starting material, malonate ester, which was conveniently functionalized leading to a variety of structures. Moreover, we also found an unexpected oxy-dearylation reaction which could be used to synthesize furanonaphthol analogs. These novel methods could be applied to a broad range of substrates to give the corresponding products in up to 83% yield. Notably, these classes of compounds exhibited more significant inhibition against protein-tyrosine phosphatase 1B (PTP1B) enzyme than a standard compound, ursolic acid.

A method for the TfOH-promoted (Tf=trifluoromethanesulfonyl) cyclization of alkyne-tethered 1,3-ketoesters to afford 2-cyclohexenone-2-carboxylate derivatives has been developed. The procedure requires no transition-metal reagent or catalyst and is practical to conduct under mild conditions. 2-Cyclohexenone-2-carboxylate derivatives were obtained in moderate to good yields without any evidence of decarboxylation. In addition, the approach can be easily adapted as a one-pot sequential cyclization/chlorination protocol that selectively provides access to 4-chloro-2-cyclohexenone-2-carboxylate derivatives in moderate to good yields.

A new approach for the synthesis of indenone derivatives using I2-promoted cyclization of ortho-alkynylarylketones has been developed. This method provides a metal-free and convenient route for regioselective synthesis of indenones employing ortho-alkynylarylketones with predefined substituents to obtain indenone products in moderate to good yields.

The combination of TMSCl and NCS generates Cl2 and HCl in situ and the E-oximes can isomerize to Z-isomers under the reaction conditions.

Regioselective synthesis of 3-bromoquinoline derivatives was achieved via a formal [4 + 2]-cycloaddition between N-aryliminium ion, generated from arylmethyl azides, and 1-bromoalkynes. This method could also be applied to other quinoline derivatives using appropriate alkynes. Moreover, the current strategy could be utilized for the diastereoselective synthesis of tetrahydroquinoline derivatives employing alkenyl substrates in good to excellent yields.

This direct azidation process provides secondary and tertiary benzyl azides in high yields and short reaction times, whereas primary benzyl alcohol (Ig) fails to react.

Zirconium(IV) chloride effectively activates nitrogen extrusion from aryl azidoacrylates followed by annulation to provide indoles at low temperature and in short reaction times.

A new and mild synthetic approach for the synthesis of 6-unsubstituted phenanthridine and phenanthridine-like compounds under metal-free conditions at room temperature has been developed. The strategy involved a tandem azide rearrangement/intramolecular annulation and oxidation reactions of biarylmethyl azide precursors to obtain the desired products in up to 99% yields with high regioselectivity.

The electrophilic agent I—Cl induces rapid cyclization of secondary enynyl alcohols (I) into dihalofurans (II).

A variety of dihydrobenzopyran derivatives is prepared by Pt(IV)-catalyzed generation of o-quinone methides and their subsequent inter- and intramolecular cycloaddition towards various dienophiles.

Reductive cyclization of aryl and vinyl iodides tethered to vinylogous acyl triflates (VATs) induces a ring-expanding fragmentation to provide cyclic alkynyl ketones, including strained nine-membered cycloalkynes, in fair to excellent yield. The tandem cyclization/C-C bond-cleavage is initiated under carefully optimized conditions by halogen-metal exchange in the presence of carbonyl and vinyl triflate functionality. A modified protocol for alkylation of 1,3-cyclohexanedione is described for preparing the relevant VAT substrates.

A variety of synthetically valuable multifunctional homopropargyl amine derivatives is prepared via reaction of dihydropyridone triflates with BuLi.

Ring-opening/C–C bond cleavage reactions induced by nucleophilic addition of methyl Grignard to 5,6-dihydro-2-pyrone (DHP) triflates 1 furnish homopropargyl alcohols (1 → 2) stereospecifically with respect to the stereochemistry of 1. Carbonyl extrusion from DHP triflates provides a unified and operationally simple strategy for preparing chiral homopropargyl alcohols.

Triethylamine (Et3N) mediates esterification reactions between the title reagent (1) and carboxylic acids. Alcohols, phenols, amides, and other sensitive functionality are not affected; a dual role for Et3N as a promoter and a scavenger is postulated. Benzyl esters are obtained from substrates including amino acid and sugar derivatives.

Synthesis of dehydrorotenoid (1) was successfully achieved via an intramolecular aldol reaction of the corresponding 1,2-diaryl diketone intermediate. The 1,2-diaryl diketone was prepared using a ruthenium-catalyzed oxidation of the corresponding substituted diaryl acetylene. Treatment of this 1,2-diketone with l -proline induced a selective intramolecular aldol condensation reaction, forming the desired benzopyranone over the alternative benzofuran. Deprotection, cyclization, and dehydration gave the target compound in good overall yield.