Total Synthesis of Lamellarin D Trimethyl Ether, Lamellarin D, and Lamellarin H

Lade, Dhanaji M.; Pawar, Amit B.; Mainkar, Prathama S.; Chandrasekhar, Srivari

doi:10.1021/acs.joc.7b00636

Cited by 49 publications

(26 citation statements)

References 43 publications

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“…The known synthetic routes to the lamellarin alkaloids published until 2014 have been reviewed [ 121 ]. Two papers describing the total synthesis of lamellarins D and H have recently been published [ 122 , 123 ].…”

Section: Alkaloidsmentioning

confidence: 99%

Ascidian Toxins with Potential for Drug Development

Watters

2018

Marine Drugs

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Ascidians (tunicates) are invertebrate chordates, and prolific producers of a wide variety of biologically active secondary metabolites from cyclic peptides to aromatic alkaloids. Several of these compounds have properties which make them candidates for potential new drugs to treat diseases such as cancer. Many of these natural products are not produced by the ascidians themselves, rather by their associated symbionts. This review will focus mainly on the mechanism of action of important classes of cytotoxic molecules isolated from ascidians. These toxins affect DNA transcription, protein translation, drug efflux pumps, signaling pathways and the cytoskeleton. Two ascidian compounds have already found applications in the treatment of cancer and others are being investigated for their potential in cancer, neurodegenerative and other diseases.

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Section: Alkaloidsmentioning

confidence: 99%

Ascidian Toxins with Potential for Drug Development

Watters

2018

Marine Drugs

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“…Syntheses of the first category include successive introduction of aryl substituents into positions 3/4/5 of the pyrrole ring (mostly by metal‐catalyzed coupling reactions) and introduction of a carboxy group into position 2 . In the second approach the pyrrole ring is formed by various methods such as Grob cyclization, Paal‐Knorr and Hantsch reactions, interaction of α‐aminoester or α‐aminonitrile with α,β‐unsaturated carbonyl compounds, [3+2] dipolar cycloaddition, metal‐catalyzed [3+2] annulation, or the reductive recyclization of pyridazines…”

Section: Introductionmentioning

confidence: 99%

Formation of 3,4‐Diarylpyrrole‐ and Pyrrolocoumarin Core of Natural Marine Products via Barton–Zard Reaction and Selective O‐Demethylation

et al. 2020

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A metal-free approach to 3,4-diarylpyrrole-2-carboxylate and pyrrolocoumarin cores of lamellarins and related natural products based on Barton-Zard reaction of nitrostilbenes with ethyl isocyanoacetate was developed. In the case of diarylpyrrole-2-carboxylates with a 3-(o-methoxyphenyl)[a] N. Scheme 1. Formation of the lactone fragment. Results and Discussion An Approach to 3,4-Diarylpyrrole CoreSurprisingly, a Barton-Zard reaction [21] (that is, base-catalyzed reaction of nitroalkenes with alkyl isocyanoacetate) has not yet been reported for synthesis of the pyrrole core of lamellarins and related compounds, [22] though such reaction with 1,2-diaryl-1-nitroethylenes should be a straightforward way of accessing 3,4-diarylpyrrole-2-carboxylates as key structural fragments of the lamellarins, ningalins, and lukianols. Scheme 2. Synthesis of Lamellarin Q Et ester. i: CNCH 2 COOEt, EtOH, K 2 CO 3 , 87 %; ii: BBr 3 (3 equiv.), CH 2 Cl 2 , 0°C, 85 %; iii: BBr 3 (2 equiv.), CH 2 Cl 2 , 0°C, 63 %; iv: 4-HOC 6 H 4 CHO, MeOH, MeNH 2 ·HCl, NaHCO 3 ; v: CNCH 2 COOEt, EtOH, K 2 CO 3 . EurJOCEuropean Journal of Organic Chemistry demethylated under the action of BBr 3 (3 equiv.) to afford lamellarin Q Et ester (Scheme 2):Noteworthy, the reaction in the presence of 2 equiv. of BBr 3[24] demonstrated a pronounced selectivity: it produced a mixture of partially demethylated products 2b and 2c in ca. 1:4 ratio. The structure of a minor product (2b) was confirmed by its alternative synthesis from 2-(4-hydroxyphenyl)-1-(4-methoxyphenyl)-1-nitroethene 1b (Scheme 2) (the latter was, in turn, prepared by condensation of 4-methoxyphenylnitromethane and 4-hydroxybenzaldehyde).Demethylation of methyl 3,4-bis(4-methoxyphenyl)pyrrole-2carboxylate 3a with excess BBr 3 (3 equiv.) furnished lamellarin Q (Scheme 3, Figure 2): Scheme 3. Synthesis of Lamellarin Q. i: BBr 3 (3 equiv.), CH 2 Cl 2 , 0°C, 84 %; ii: MeONa, reflux, 84 %; iii: CNCH 2 COOEt, MeOH, K 2 CO 3 , 89 %.Figure 2. Molecular structure of Lamellarin Q·MeCN (50 % ellipsoids).

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“…5-Aryl 1 H -Pyrrole-2-carboxylate esters constitute an important class of pyrrole derivatives [ 1 , 2 ]. This structural motif is present in several natural products and their analogs such as Lamellarins [ 3 , 4 , 5 , 6 , 7 ] (topoisomerase I inhibitor, MDR reversal agent, and anti-HIV agent), and arylated hymenialdisine [ 8 , 9 ] (ChK2 inhibitor), as well as in several other biologically active compounds with anti-HIV [ 10 , 11 , 12 , 13 , 14 ], antibacterial [ 15 ], antimitotic [ 16 ], and cytotoxic [ 17 ] activities ( Figure 1 ). 5-Aryl 1 H -Pyrrole-2-carboxylate esters and their derivatives have also found applications, for example, as organic fluorescent materials [ 18 , 19 ], anion receptors/molecular logic gates [ 20 ], and as building blocks for metal organic frameworks [ 21 ] and helical asymmetric architectures [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Facile Synthesis of NH-Free 5-(Hetero)Aryl-Pyrrole-2-Carboxylates by Catalytic C–H Borylation and Suzuki Coupling

et al. 2020

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A convenient two-step preparation of NH-free 5-aryl-pyrrole-2-carboxylates is described. The synthetic route consists of catalytic borylation of commercially available pyrrole-2-carboxylate ester followed by Suzuki coupling without going through pyrrole N–H protection and deprotection steps. The resulting 5-aryl substituted pyrrole-2-carboxylates were synthesized in good- to excellent yields. This synthetic route can tolerate a variety of functional groups including those with acidic protons on the aryl bromide coupling partner. This methodology is also applicable for cross-coupling with heteroaryl bromides to yield pyrrole-thiophene, pyrrole-pyridine, and 2,3’-bi-pyrrole based bi-heteroaryls.

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Total Synthesis of Lamellarin D Trimethyl Ether, Lamellarin D, and Lamellarin H

Cited by 49 publications

References 43 publications

Ascidian Toxins with Potential for Drug Development

Ascidian Toxins with Potential for Drug Development

Formation of 3,4‐Diarylpyrrole‐ and Pyrrolocoumarin Core of Natural Marine Products via Barton–Zard Reaction and Selective O‐Demethylation

Facile Synthesis of NH-Free 5-(Hetero)Aryl-Pyrrole-2-Carboxylates by Catalytic C–H Borylation and Suzuki Coupling

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