Efficient total synthesis of neocryptolepine and synthetic access to 6-methylquinindoline from a common intermediate

Méndez, María Virginia; Heredia, Daniel A.; Larghi, Enrique L.; Bracca, Andrea B. J.; Kaufman, Teodoro S.

doi:10.1039/c7ra05349e

Cited by 22 publications

(10 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The oldest fashion involved the extension of an indole moiety from a functionalized quinoline through the C–C or the C–N coupling . Although modification toward various coupling processes has been carried out, this strategy has often been reported in synthesizing a solo case of neocryptolepine or with a limited scope of natural alkaloid derivatives . The dual annulation of an N -alkynylaryl- N -aryl carbodiimide through a diradical pathway is another method for the synthesis of quinindolines that has appeared occasionally in the literature .…”

mentioning

confidence: 99%

Palladium-Catalyzed Dual Annulation: A Method for the Synthesis of Norneocryptolepine

et al. 2019

View full text Add to dashboard Cite

A novel procedure for the Pd-catalyzed dual annulation reaction to synthesize the norneocryptolepine derivatives involving the concerted construction of two central heterocycles is reported. The further methylation of the norneocryptolepine to afford its alkaloid analog neocryptolepine implies that synthesis of various neocryptolepine derivatives is feasible. The oxidative addition of Pd(0) is indicated as the key step to activate the intramolecular addition of nitrile according to the mechanism study.

show abstract

mentioning

confidence: 99%

Palladium-Catalyzed Dual Annulation: A Method for the Synthesis of Norneocryptolepine

et al. 2019

View full text Add to dashboard Cite

show abstract

“…6-Methyl-6H-indolo [2,3-b]quinoline (1d). 17 Purification by column chromatography on silica gel [R f value = 0.8 (10% ethyl acetate in petroleum ether)] to afford 1d as an orange solid (82.5 mg, yield 79%), mp: 82−84 °C; 1 H NMR (CDCl 3 , 600 MHz): δ 8.74 (s, 1H), 8.17 (t, J = 9.6, 2H), 8.03 (d, J = 8.6 Hz, 1H), 7.74 (t, J = 8.2 Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.48 (t, J = 7.4 Hz, 1H), 7.45 (d, J = 8.1 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 4.02 (s, 3H); 13 C{ 1 H} NMR (CDCl 3 , 150 MHz): δ 152. 3, 146.3, 142.4, 128.4, 128.0, 127.6, 126.9, 126.9, 123.6, 122.4, 120.9, 119.9, 119.5, 117.7, 108.2, 27.3 Gram-Scale Synthesis of Products 6a and 6d.…”

Section: -Benzyl-2-(trifluoromethyl)-6h-indolo[23-b]quinoline (6af)mentioning

confidence: 99%

One-Pot Cascade Annulation-Triggered Synthesis of N-6-Substituted Norcryptotackieine Alkaloids and Evaluation of Their Antileishmanial Activities

et al. 2022

View full text Add to dashboard Cite

Norcryptotackieine or 6H-indolo [2,3-b]quinoline is an indoloquinoline class of alkaloid isolated from Cryptolepis sanguinolenta that is traditionally used for antimalarial therapy. Additional structural tuning can extend the therapeutic potency of these indoloquinolines as antileishmanial drug leads. Synthesis of N-6-functionalized norcryptotackieines suffers from the necessity of complex pre-synthesized starting materials, restricted scope of functionalization, or tedious processes. Consequently, a straightforward synthetic procedure for accessing non-natural N-6-functionalized 6H-indolo[2,3-b]quinolines with potent antileishmanial activities is highly sought-after. Herein, we report a two-step one-pot synthesis of N-6-functionalized norcryptotackieine through a Pd-catalyzed double annulation reaction of commercially available amphipathic amines, 2-iodobenzyl cyanide, and differently functionalized 2-bromobenzaldehydes. The reported procedure allows a broad flexibility of substitution at the N-6 position and access to diversified scaffolds, including two natural products norcryptotackieine and neocryptolepine. Interestingly, 6d showed potent antileishmanial activities by causing disruption in the cytoskeletal structure and apoptotic-mediated death of parasites. Together, our work manifests the shortest route to N-6-substituted norcryptotackieine-derived antileishmanial agents.

show abstract

“…1 H NMR (300 MHz, CDCl 3 /TMS): δ = 7.13 (s, 1 H, H-4), 6.52 (d, J = 2.3 Hz, 1 H, H-7), 6.41 (d,J = 2.3 Hz,1 H,, 3.91 (s, 3 H, OCH 3 -8), 3.89 (s, 3 H, OCH 3 -6), 3.00 (s, 3 H, CH 3 -1), 2.55 (s, 3 H, CH 3 -3).…”

Section: 8-dimethoxy-13-dimethylisoquinoline (1)mentioning

confidence: 99%

Total Synthesis and Cytotoxic Activity of 6,8-Dimethoxy-1,3-dimethylisoquinoline Isolated from Ancistrocladus tectorius: A 6π-Azaelectrocyclization Approach

et al. 2018

Self Cite

View full text Add to dashboard Cite

A facile and convenient approach toward the total synthesis of 1,3-dimethyl-6,8-dimethoxyisoquinoline from phloroacetophenone is reported. The sequence entailed the selective 2,4-di-O-methylation and further triflation of the resulting phenolic product. This was followed by a Stille-type allylation, an allyl-to-propenyl isomerization, and the methoximation of the carbonyl moiety. A final microwave-assisted 6π-azaelectrocyclization completed the sequence. Functionalized derivatives on C-1 were also prepared. The heterocycles exhibited cytotoxic activity.

show abstract

Efficient total synthesis of neocryptolepine and synthetic access to 6-methylquinindoline from a common intermediate

Abstract: The total synthesis of neocryptolepine and the synthesis of its non-natural isomer 6-methyl quinindoline were efficiently achieved in a few steps from a common intermediate.

Cited by 22 publications

References 102 publications

Palladium-Catalyzed Dual Annulation: A Method for the Synthesis of Norneocryptolepine

Palladium-Catalyzed Dual Annulation: A Method for the Synthesis of Norneocryptolepine

One-Pot Cascade Annulation-Triggered Synthesis of N-6-Substituted Norcryptotackieine Alkaloids and Evaluation of Their Antileishmanial Activities

Total Synthesis and Cytotoxic Activity of 6,8-Dimethoxy-1,3-dimethylisoquinoline Isolated from Ancistrocladus tectorius: A 6π-Azaelectrocyclization Approach

Contact Info

Product

Resources

About