Synthesis of the isoquinoline alkaloid, crispine C

Blair, Adele; Stevenson, Louise; Sutherland, Andrew

doi:10.1016/j.tetlet.2012.05.113

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…Our synthesis began with the preparation of amide 18 in 82% yield through an EDCI coupling of commercially available 2-(3,4-dimethoxyphenyl)ethan-1-amine and N -Cbz-4-aminobutyric acid ( 17 ) (Scheme ). Attempted Bischler–Napieralski reaction of amide 18 with either neat POCl 3 at 110 °C as reported by Sutherland, or POCl 3 /CH 3 CN at 82 °C failed to produce the dihydroisoquinoline. Instead, we observed byproducts resulting from cyclization of the N -Cbz-protected primary amine onto the amide (see Supporting Information for further information).…”

Section: Resultsmentioning

confidence: 93%

“…5 A total synthesis of 12 was reported using a Henry reaction and Pictet−Gams modification of the Bischler−Napieralski reaction as key steps to deliver the natural product in 7 steps from 3,4-dimethoxybenzaldehyde. 6 Asymmetric syntheses of both natural (+)-crispine E and the unnatural enantiomer were also reported. 7 The first synthesis of (+)-crispine E was reported in 2008 employing a Noyori asymmetric transfer hydrogenation (ATH) reaction.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Crispines A and B have a pyrrolo[2,1- a ]isoquinoline skeleton, while crispines C–E ( 12 - 14 ) are isoquinoline-derived natural products bearing guanidine side chains that are also structurally related to 4 and 11 . A total synthesis of 12 was reported using a Henry reaction and Pictet–Gams modification of the Bischler–Napieralski reaction as key steps to deliver the natural product in 7 steps from 3,4-dimethoxybenzaldehyde . Asymmetric syntheses of both natural (+)-crispine E and the unnatural enantiomer were also reported .…”

Section: Introductionmentioning

confidence: 99%

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Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities

Sakai,

Matsumura,

Uchimasu

et al. 2024

J. Org. Chem.

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Mellpaladines A−C (1−3) and dopargimine (4) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1carboxydopargimine (5), three additional mellpaladines D−F (6− 8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5′-dihydroxy-4,4′-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine ( 16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1−4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).

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Section: Resultsmentioning

confidence: 93%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities

Sakai,

Matsumura,

Uchimasu

et al. 2024

J. Org. Chem.

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“…Acid hydrolysis of the dichloromethylacetamide group required forcing conditions but did yield the corresponding amine cleanly. This was coupled with commercially available N , N ′-bis( tert -butoxycarbonyl)-1 H -pyrazole-1-carboxamidine ( 22 ) in the presence of Hünig’s base, and this gave guanidine 23 in 75% yield over the two steps. , Finally, removal of the Boc-protecting groups using TFA completed the 10-step synthesis of hypotensive agent 4 in 40% overall yield from commercially available 4-chloro-2-hydroxybenzaldehyde ( 5i ).…”

Section: Resultsmentioning

confidence: 99%

One-Pot Synthesis of 5-Amino-2,5-dihydro-1-benzoxepines: Access to Pharmacologically Active Heterocyclic Scaffolds

et al. 2015

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A one-pot multibond-forming process involving a thermally mediated Overman rearrangement and a ring closing metathesis reaction of allylic trichloroacetimidates bearing a 2-allyloxyaryl group has been developed for the synthesis of 5-amino-substituted 2,5-dihydro-1-benzoxepines. Chemoselective reduction and functionalization of these compounds allowed access to a range of pharmacologically active 5-amino-2,3,4,5-tetrahydro-1-benzoxepine scaffolds.

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Quinolines and Isoquinolines

Finley

2015

Kirk-Othmer Encyclopedia of Chemical Technology

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The fusion of a pyridine and a benzene ring produces two heterocyclic aromatic systems usually referred to by their common names, quinoline and isoquinoline. In addition to the chemistry to be expected, this combination opens a wide range of additional possibilities. It is therefore not surprising that both quinoline and isoquinoline have been the subject of extensive studies ranging from the theoretical to the most applied. The dye and photographic industries, the metallurgical, analytical, and polymer sciences all provide extensive examples. However, it continues to be the medical field and the pharmaceutical industry that provides the major driving force for an impressive array of studies of the synthesis and properties of molecules containing these structures. The toxicity of these compounds is sufficient to warrant care in their handling.

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Synthesis of the isoquinoline alkaloid, crispine C

Cited by 7 publications

References 38 publications

Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities

Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities

One-Pot Synthesis of 5-Amino-2,5-dihydro-1-benzoxepines: Access to Pharmacologically Active Heterocyclic Scaffolds

Quinolines and Isoquinolines

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