Total Synthesis of Natural and Unnatural Lamellarins with Saturated and Unsaturated D-Rings

Lamellarins are a large family of marine alkaloids with potential anticancer activity that have been isolated from diverse marine organisms, mainly ascidians and sponges. All lamellarins feature a 3,4-diarylpyrrole system. Pentacyclic lamellarins, whose polyheterocyclic system has a pyrrole core, are the most active compounds. Some of these alkaloids are potently cytotoxic to various tumor cell lines. To date, Lam-D and Lam-H have been identified as lead compounds for the inhibition of topoisomerase I and HIV-1 integrase, respectively-nuclear enzymes which are over-expressed in deregulation disorders. Moreover, these compounds have been reported for their efficacy in treatment of multi-drug resistant (MDR) tumors cells without mediated drug efflux, as well as their immunomodulatory activity and selectivity towards melanoma cell lines. This article is an overview of recent literature on lamellarins, encompassing their isolation, recent synthetic strategies for their total synthesis, the preparation of their analogs, studies on their mechanisms of action, and their structure-activity relationships (SAR).

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“…The same methodology was used to prepare several natural saturated and unsaturated lamellarins, as well as various analogs [18]. …”

Section: A) Pyrrole Ring Formationmentioning

confidence: 99%

Recent Advances in Lamellarin Alkaloids: Isolation, Synthesis and Activity

Plá¹,

Alberício²,

Álvarez

2008

ACAMC

106

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“…2-Aryl-1-carboethoxy-1-nitroethenes 1 were prepared according to reported procedure. 22 Triazoles 2a, 2c, 2e, 2f and 2g are known compounds. 15 Triazoles 2b, 2d and 2h-j are new compounds and their physical and spectral properties are reported in Supplementary Information section.…”

Section: Methodsmentioning

confidence: 99%

Efficient synthesis of functionalized 1,2,3-triazoles by catalyst-free 1,3-dipolar cycloaddition of nitroalkenes with sodium azide

Wang¹,

Hu²,

Huang³

et al. 2012

J. Braz. Chem. Soc.

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Foi desenvolvido um protocolo simples e eficiente para a síntese de derivados de 1,2,3-triazol pela cicloadição 1,3-dipolar de nitroalquenos com azida de sódio, sem a necessidade de catalisador e sob condições brandas.A simple and efficient protocol has been developed for the synthesis of 1,2,3-triazole derivatives by catalyst-free 1,3-dipolar cycloaddition of nitroalkenes with sodium azide under mild conditions. Keywords: 1,2,3-triazoles, 1,3-dipolar cycloaddition, 3-nitrocoumarins, sodium azide, catalyst-free IntroductionFive-membered nitrogen heterocycles play an important role in biological systems. Among these, the 1,2,3-triazoles and their derivatives are of considerable interest as they possess a wide range of biological properties, such as anti-HIV, 1 anti-allergic, 2 anti-fungal, 3 anti-viral 4 and anti-microbial activity. 5 1,2,3-Triazoles are important in pharmacological applications due to its stability toward light, moisture, oxygen, and metabolism in the body. 6 In addition, these moieties are widely applied as photosensitizers, dyes, 7 and commercially employed as anti-corrosive agents 8 in industry. Owing to the importance of these compounds, a variety of methods are known in the literature for the synthesis of pyrazoles, which include the thermal 1,3-dipolar cycloaddition of azide with various alkynes 9 and cycloaddition reactions of terminal alkynes with alkyl azides using Cu(I) as catalyst. 10 In addition, these molecules can also be prepared in one-pot procedure from alkynes with azides. 11 In fact, a straightforward approach to 1,2,3-triazoles is interesting and catalystfree intermolecular 1,3-dipolar cycloaddition azides with electron-deficient alkenes to afford 1,2,3-triazoles, has been the subject of intensive research. 12 Recently, sodium azide has been used as a 1,3-dipole in 1,3-dipolar cycloaddition for the synthesis of 1,2,3-triazoles. 12 Considering the above reports and encouraged by the good results, we envisaged that 1,3-dipolar cycloaddition would be possible between the α-carbonyl-β-aryl analogs of nitroethene with sodium azide, as outlined in Scheme 1. First, the reaction was happened via 1,3-dipolar cycloaddition of nitroalkenes with sodium ion as the key step. Then, elimination of the NaNO 2 and migration of hydrogen atom afford 1,2,3-triazoles. Results and DiscussionCoumarins are important heterocycles widely present in natural products exhibiting a broad range of biological and therapeutic activities and have been the subject of intensive research. 13 Recently, we have demonstrated the usefulness of the catalyst-free intermolecular 1,3-dipolar cycloaddition of 3-nitrocoumarins in the synthesis of functionalized pyrazoles with good yields. 14 We considered that the incorporation of a 1,2,3-triazole heterocyclic unit into 3-nitrocoumarins might provide 1,2,3-triazole derivatives that have important biological and pharmaceutical activities. Thus, we turned our attention to the possible synthesis of 1,2,3-triazoles using 3-nitrocoumarins 1 as dipolarophiles for the electron-po...

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“…In 2001, Ruchirawat and Mutarapat reported an efficient synthesis of lamellarin G trimethyl ether (32) starting from 3,4-dihydro-1-benzylisoquinoline (27) (Scheme 4). 25 Reaction of 27 with phenacyl bromide (28) in the presence of potassium carbonate in acetonitrile gave 5,6-dihydropyrrolo[2,1-a]isoquinoline (29) via N-alkylation of 27 with 28 followed by intramolecular condensation of the resulting enamine with carbonyl moiety (Tschitschibabin reaction 26 ).…”

Section: -1-3 Synthesis By Ruchirawatmentioning

confidence: 99%

“…Vilsmeier reaction of 29 followed by alkaline hydrolysis of the mesyl group gave hydroxy-aldehyde (31a) in good yield. Oxidation of 31a with manganese dioxide via the putative cyclic hemiacetal (31b) gave lamellarin G trimethyl ether (32) Perkin condensation of arylacetic acids (51) and benzaldehydes (52) gave stilbenic acids (53). These acids were converted to 3,4-dihydroisoquinolines (56) via amides (55) using standard Bischler-Napieralski reaction.…”

Section: -1-3 Synthesis By Ruchirawatmentioning

confidence: 99%