Asymmetric synthesis of 1-alkyltetrahydroisoquinolines using chiral oxazolo[2,3-a]tetrahydroisoquinolines

Yamato, Masatoshi; Hashigaki, Kuniko; Qais, Nazmul; Ishikawa, S.

doi:10.1016/s0040-4020(01)87916-3

Cited by 62 publications

(15 citation statements)

References 12 publications

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“…(–)‐Norcryptostyline II (7d): Following the above general procedure, from lactam 6d (90 mg, 0.26 mmol) in THF (3 mL), NaBH 4 (24.8 mg, 0.66 mmol) in THF (4 mL), and I 2 (66.5 mg, 0.26 mmol) in THF (3 mL), tetrahydroisoquinoline 7 d (58 mg, 69 %) was obtained as a yellow oil after flash chromatography by using a cartridge containing amine‐functionalized silica (1:1 hexane/EtOAc). [ α ] D 22 = –33.8 ( c = 0.36, CHCl 3 ) {ref 5a. [ α ] D 18 = –37 ( c = 0.26, CHCl 3 )}.…”

Section: Methodsmentioning

confidence: 99%

A General Methodology for the Enantioselective Synthesis of 1‐Substituted Tetrahydroisoquinoline Alkaloids

et al. 2010

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Starting from tricyclic lactam 2, which is easily accessible by cyclocondensation of δ‐oxoester 1 with (R)‐phenylglycinol, a three‐step synthetic route to enantiopure 1‐substituted tetrahydroisoquinolines, including 1‐alkyl‐, 1‐aryl‐, and 1‐benzyltetrahydroisoquinoline alkaloids, as well as the tricyclic alkaloid (–)‐crispine A, has been developed. The key step is a stereoselective α‐amidoalkylation reaction using the appropriate Grignard reagent.

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Section: Methodsmentioning

confidence: 99%

A General Methodology for the Enantioselective Synthesis of 1‐Substituted Tetrahydroisoquinoline Alkaloids

et al. 2010

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“…A similar case was also observed in the preparation of 2-(2-bromoethyl)-4,5-dimethoxybenzaldehyde by bromination of 6,7-dimethoxy isochroman. 27) For the reason above, Yamato et al established a two-step approach to 2-(2-bromoethyl)-4,5-dimethoxybenzaldehyde involving the treatment of 6,7-dimethoxyisochroman with ethyl orthoformate in the presence of BF 3 at −78°C followed by treatment with acetyl bromide, but the total yield was only 13%. 27) Recently, a new approach to dihydroisoquinolinium salts was reported involving N-arylation of tetrahydroisoquinoline followed by N-bromosuccinimide (NBS) mediated oxidation 26) (Chart 2).…”

mentioning

confidence: 99%

Synthesis and <i>in Vitro</i> Antifungal Activities of New 2-Aryl-6,7-methylenedioxy-3,4-dihydroisoquinolin-2-ium Bromides

Yang

Yao

Qin

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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2-Aryl-3,4-dihydroisoquinolin-2-iums might be considered as a class of simple analogues of natural quaternary benzo[c]phenanthridine alkaloids. In this paper, 26 new 2-aryl-6,7-methylenedioxy-3,4-dihydroisoquinolin-2-ium bromides with various substituents in N-aromatic ring were synthesized from commercially available 1,3-benzodioxole in good to excellent yields. All the compounds were elucidated by MS, high resolution (HR)-MS, IR, 1 H-and 13 C-NMR analysis, and evaluated for antifungal activities in vitro against Alternaria alternate, Curvularia lunata and Fusarium oxysporum sp. niveum at 50 µg/mL. Most of the compounds showed higher activities against all the test fungi than their natural model compounds sanguinarine and chelerythrine. For A. alternate and Curvularia lunata, most of them were also more active than thiabendazole, a commercial fungicide standard. The structure-activity relationship indicated that the substituent in N-aromatic ring and its position had significant effect on the activity. The general trend was that halogen atoms and CF 3 remarkably enhanced the activity while CH 3 and OCH 3 decreased the activity. Generally, osubstituted isomers were more active than m-and p-substituted isomer. The present results suggest that the title compounds are potential for the development of new isoquinoline antimicrobial agents.Key words 3,4-dihydroisoquinolinium; 1,2,3,4-tetrahydroisoquinoline; N-heterocyclization; antifungal activity; CuCl 2 -catalyzed oxidative coupling reaction; 2,3-dichloro-5,6-dicyano-1,4-benzoquinone oxidation Alkaloids represent a very extensive group of secondary metabolites with diverse structures, distribution in nature, and biological effects. Natural isoquinolines are one of the largest groups of alkaloids. Among them, there is a relatively small but important class of iminium moiety-containing isoquinoline alkaloids, such as quaternary benzo[c] phenanthridine alkaloids (QBAs), quaternary N-naphthyl isoquinolines, berberines and so on 1,2) (Fig. 1). In the past decades, these compounds have aroused interests of both chemists and pharmacologists for their chemical reactivity and extensive bioactivities including antitumor, [3][4][5] antimicrobial, [6][7][8][9][10][11][12] anti-inflammation, 13) antiplatelet aggregation, 14) anti-angiogenesis, 15) anti-acetylcholinesterase, 16) and antiparasite activities. [17][18][19][20] Our previous studies demonstrated that sanguinarine and chelerythrine ( Fig. 1) might serve as ideal lead compounds to develop new isoquinoline antimicrobial and acaricidal agents. Meanwhile, the iminium moiety (C= N + ) was their determinant for their bioactivities. 11,12,17) The similar cases were also found for antitumor activity of 7-demethyl chelerythrine (NK109) 21) and antibacterial activity of berberine.9) In addition, the molecular planarity was also proven to be an important factor for the activity.21) Based on understanding of the structure-activity relationship above and the aim of developing more potent QBAs-like drugs, we intended to design a cl...

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“…Chiral sulfinamide 48 has also been utilized in the asymmetric synthesis of (-)-α-HTBZ, as shown in Scheme 10 [62]. Known chloroaldehyde 47 [63] was condensed with sulfinamide 48 to afford chiral imine 49 in the presence of copper sulfate [64]. The electrophilic imine 49 was then converted into homoallylic amine 50 via an allylation reaction.…”

Section: Asymmetric Synthesis Of (+)-Tbzmentioning

confidence: 99%

Synthesis of Tetrabenazine and Its Derivatives, Pursuing Efficiency and Selectivity

Paek

2020

Molecules

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Tetrabenazine is a US Food and Drug Administration (FDA)-approved drug that exhibits a dopamine depleting effect and is used for the treatment of chorea in Huntington’s disease. Mechanistically, tetrabenazine binds and inhibits vesicular monoamine transporter type 2, which is responsible for importing neurotransmitters from the cytosol to the vesicles in neuronal cells. This transportation contributes to the release of neurotransmitters inside the cell to the synaptic cleft, resulting in dopaminergic signal transmission. The highly potent inhibitory activity of tetrabenazine has led to its advanced applications and in-depth investigation of prodrug design and metabolite drug discovery. In addition, the synthesis of enantiomerically pure tetrabenazine has been pursued. After a series of research studies, tetrabenazine derivatives such as valbenazine and deutetrabenazine have been approved by the US FDA. In addition, radioisotopically labeled tetrabenazine permits the early diagnosis of Parkinson’s disease, which is difficult to treat during the later stages of this disease. These applications were made possible by the synthetic efforts aimed toward the efficient and asymmetric synthesis of tetrabenazine. In this review, various syntheses of tetrabenazine and its derivatives have been summarized.

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Asymmetric synthesis of 1-alkyltetrahydroisoquinolines using chiral oxazolo[2,3-a]tetrahydroisoquinolines

Cited by 62 publications

References 12 publications

A General Methodology for the Enantioselective Synthesis of 1‐Substituted Tetrahydroisoquinoline Alkaloids

A General Methodology for the Enantioselective Synthesis of 1‐Substituted Tetrahydroisoquinoline Alkaloids

Synthesis and <i>in Vitro</i> Antifungal Activities of New 2-Aryl-6,7-methylenedioxy-3,4-dihydroisoquinolin-2-ium Bromides

Synthesis of Tetrabenazine and Its Derivatives, Pursuing Efficiency and Selectivity

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