Construction of Pentacyclic Lamellarin Skeleton via Grob Reaction: Application to Total Synthesis of Lamellarins H and D

Manjappa, Kiran B.; Lin, Jhih-Min; Yang, Ding‐Yah

doi:10.1021/acs.joc.7b01061

Cited by 52 publications

(27 citation statements)

References 34 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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“…Current research suggests that lamellarin D ( 1 ) mediates apoptosis by activation of several non‐related signaling pathways such as inhibition of mitochondrial respiration in tumor cells,, inhibition of topoisomerase I,, and Induction of intracellular ROS‐production . Because of their attractive properties, the synthesis and evaluation of lamellarins is still of current interest , …”

Section: Introductionmentioning

confidence: 99%

“…[23] Because of their attractive properties, the synthesis and evaluation of lamellarins is still of current interest. [21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]…”

Section: Introductionmentioning

confidence: 99%