A New Route to α-carbolines Based on 6π-electrocyclization of Indole-3-alkenyl Oximes

Overview

Journal Org Lett

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2013 Nov 28

PMID 24280001

Citations 2

Authors

Sophie J Markey

William Lewis

Christopher J Moody

Affiliations

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Abstract

Indoles are converted into α-carbolines in four steps by acylation at C-3, Boc-protection, olefination of the resulting 3-indolyl aldehydes or ketones to give N-Boc-3-indolyl alkenyl oxime O-methyl ethers, which upon heating to 240 °C under microwave irradiation undergo loss of the Boc-group, and 6π-electrocyclization to α-carbolines, following aromatization by loss of methanol (11 examples, 30-90% yield).

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References

Airaksinen M, Kari I . Beta-carbolines, psychoactive compounds in the mammalian body. Part I: Occurrence, origin and metabolism. Med Biol. 1981; 59(1):21-34. View

Kumar A, Nagarajan R . Synthesis of α-carbolines via Pd-catalyzed amidation and Vilsmeier-Haack reaction of 3-acetyl-2-chloroindoles. Org Lett. 2011; 13(6):1398-401. DOI: 10.1021/ol2000827. View

Laha J, Petrou P, Cuny G . One-pot synthesis of alpha-carbolines via sequential palladium-catalyzed aryl amination and intramolecular arylation. J Org Chem. 2009; 74(8):3152-5. DOI: 10.1021/jo802776m. View

Pahan K . Lipid-lowering drugs. Cell Mol Life Sci. 2006; 63(10):1165-78. PMC: 1986656. DOI: 10.1007/s00018-005-5406-7. View

Miyake F, Yakushijin K, Horne D . Biomimetic synthesis of grossularines-1. Angew Chem Int Ed Engl. 2005; 44(21):3280-2. DOI: 10.1002/anie.200500055. View

Vera-Luque P, Alajarin R, Alvarez-Builla J, Vaquero J . An improved synthesis of alpha-carbolines under microwave irradiation. Org Lett. 2006; 8(3):415-8. DOI: 10.1021/ol052552y. View

Gupta S, Kumar B, Kundu B . Three-component tandem reaction involving acid chlorides, terminal alkynes, and 2-aminoindole hydrochlorides: synthesis of α-carboline derivatives in aqueous conditions via regioselective [3 + 3] cyclocondensation. J Org Chem. 2011; 76(24):10154-62. DOI: 10.1021/jo201994v. View

Portela-Cubillo F, Scott J, Walton J . Microwave-assisted preparations of dihydropyrroles from alkenone O-phenyl oximes. Chem Commun (Camb). 2007; (39):4041-3. DOI: 10.1039/b712582h. View

Peduto A, More V, de Caprariis P, Festa M, Capasso A, Piacente S . Synthesis and cytotoxic activity of new β-carboline derivatives. Mini Rev Med Chem. 2011; 11(6):486-91. DOI: 10.2174/138955711795843383. View

10.

Cao R, Peng W, Wang Z, Xu A . beta-Carboline alkaloids: biochemical and pharmacological functions. Curr Med Chem. 2007; 14(4):479-500. DOI: 10.2174/092986707779940998. View

11.

Ueshima K, Akihisa-Umeno H, Nagayoshi A, Takakura S, Matsuo M, Mutoh S . Implitapide, a microsomal triglyceride transfer protein inhibitor, reduces progression of atherosclerosis in apolipoprotein E knockout mice fed a Western-type diet: involvement of the inhibition of postprandial triglyceride elevation. Biol Pharm Bull. 2005; 28(2):247-52. DOI: 10.1248/bpb.28.247. View

12.

Kumar A, Rao P, Nagarajan R . Synthesis of pyrido[2,3-b]indoles and pyrimidoindoles via Pd-catalyzed amidation and cyclization. Org Biomol Chem. 2012; 10(26):5084-93. DOI: 10.1039/c2ob25371b. View

13.

Portela-Cubillo F, Surgenor B, Aitken R, Walton J . Thermal rearrangement of indolyl oxime esters to pyridoindoles. J Org Chem. 2008; 73(20):8124-7. DOI: 10.1021/jo801751a. View