Versatility of Substituted 1‐Formyl‐9H‐β‐carbolines for the Synthesis of New Fused β‐Carbolines via Intramolecular 1,3‐Dipolar Cycloaddition

Abstract

Substituted 1‐formyl‐9H‐β‐carbolines are demonstrated to be viable precursors for the synthesis of a library of new β‐carboline‐based polycyclic systems via 1,3‐dipolar cycloaddition strategy.

Facile Synthesis of Dihydroquinoline‐Fused Canthines by Intramolecular Aza‐Diels–Alder Reaction

“…[6] Interestingly, the 1 H NMR spectrum of crude 4a indicated that the reaction was diastereoselective and favoured the formation of the syn isomer. This conclusion was based on the coupling constant associated with the CHOH proton, which was observed to be 1.8 Hz for the syn isomer and 8.0 Hz for the anti isomer (see below).…”

“…[1] Aiming to diversify the range of D-ring-fused β-carbolines using cycloaddition reactions as a key step, we now report the synthesis of dihydroquinoline-fused canthines through aza-Diels-Alder reactions between N-prenylated 1-formyl-9H-β-carbolines and anilines in the presence of a Lewis acid, followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Such dihydroquinoline-fused canthines are analogous to Lavendamycin-based compounds, which elicit potent cytotoxic activity.…”

One-Pot Conversion of 1-Bromo-β-carboline and 1-Bromocarbazole into Pentacyclic­ Compounds by Suzuki Cross-Coupling Followed by Spontaneous Cyclization

“…11 Further approaches utilized heteroannulation reactions on 5,6-dihydrocanthin-4-one 14 for the preparation of pyrimidino and quinolino congeners of C and thermolysis of an azidoarene to generate a indolo-canthin-6-one. 15 Isoxazole-and pyrrole-annulated canthin-4-ones were obtained by intramolecular 1,3-dipolar cycloadditions, 16 whereas an attempted intramolecular hetero-Diels-Alder cycloaddition of a vinylindole failed to give the desired pentacyclus of type C. 17 Markgraf et al 11 reported an unsuccessful attempt to prepare benzocanthin-6-ones of type C starting from 1-chloro-β-carboline and 2-methoxycarbonylphenylboronic acid, which should comprise a Suzuki cross-coupling 18 and subsequent intramolecular N-acylation at the pyrrole nitrogen. In a project aimed at the synthesis of pentacycles of types C and D with high flexibility in ring E and without the problems associated with obtaining poorly separable isomeric mixtures, we reinvestigated the latter approach.…”

1-Formyl-9H-β-Carboline: A Useful Scaffold for Synthesizing Substituted- and Fused β-Carbolines

“…Application of Sharpless oxidation allowed Hibino and coworkers to accomplish the first enantioselective total synthesis of (+)-oxopropaline D (27) and its enantiomer in 13.4% overall yield from 19 [19]. A sequence of nine-steps using the common key compound, N-MOM-1-methoxycarbonyl-4-methyl--carboline (19) that was prepared by thermal electrocyclic reaction of a 1azahexatriene system (17) involving the 2,3-bond of indole led to the formation of (+)-oxopropaline D with 93% ee (Scheme 7).…”

“…Substituted 1-formyl-9H--carbolines were successfully employed as intermediate for the synthesis of a library of newcarboline-based polycyclic systems via 1,3-dipolar cycloaddition reaction [27]. The installation of dienophile in the form of allyl or propargyl in 1-formyl-9H--carbolines (2, 9 and 56) was achieved through a modified route via initial N-alkylation of acetal 55 with allyl or propargyl bromide to generate 68-69 followed by deprotection of formyl group to afford the N-substituted derivatives (70-71).…”