A Stereoselective Approach toward (−)-Lepadins A–C

Xiong, Lixia; Hu, Lingling; Jia, Junhao; He, Gu; Jia, Yuanliang; Chen, Xiaochuan

doi:10.1021/acs.orglett.7b02647

Cited by 18 publications

(10 citation statements)

References 38 publications

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“…Thus, lepadins may represent a promising class of marine natural products for the development of novel therapeutic agents. Alongside these interesting and varied pharmacological activities, the limited amounts of natural metabolites which can be isolated by complex screening procedures with the risk to have altered biological responses, as well as the hard issue to solve the definitive configurational assignments, have encouraged several researchers to undertake synthetic protocols for obtaining lepadins [13][14][15][16]. However, the synthesis of lepadins requires a conspicuous number of highly stereoselective synthetic steps which represents a not easily accessible route for obtaining the native metabolites.…”

Section: Introductionmentioning

confidence: 99%

Insights into Cytotoxic Behavior of Lepadins and Structure Elucidation of the New Alkaloid Lepadin L from the Mediterranean Ascidian Clavelina lepadiformis

et al. 2022

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The chemical investigation of the Mediterranean ascidian Clavelina lepadiformis has led to the isolation of a new lepadin, named lepadin L, and two known metabolites belonging to the same family, lepadins A and B. The planar structure and relative configuration of the decahydroquinoline ring of lepadin L were established both by means of HR-ESIMS and by a detailed as extensive analysis of 1D and 2D NMR spectra. Moreover, microscale derivatization of the new alkaloid lepadin L was performed to assess the relative configuration of the functionalized alkyl side chain. Lepadins A, B, and L were tested for their cytotoxic activity on a panel of cancer cell lines (human melanoma [A375], human breast [MDA-MB-468], human colon adenocarcinoma [HT29], human colorectal carcinoma [HCT116], and mouse myoblast [C2C12]). Interestingly, a deeper investigation into the mechanism of action of the most cytotoxic metabolite, lepadin A, on the A375 cells has highlighted its ability to induce a strongly inhibition of cell migration, G2/M phase cell cycle arrest and a dose-dependent decrease of cell clonogenity, suggesting that it is able to impair self-renewing capacity of A375 cells.

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Section: Introductionmentioning

confidence: 99%

Insights into Cytotoxic Behavior of Lepadins and Structure Elucidation of the New Alkaloid Lepadin L from the Mediterranean Ascidian Clavelina lepadiformis

et al. 2022

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“…For the type III lepadins,s of ar only two approaches have been developed by the groups of Blechert [14] andH sung [15] independently.M oreover,t he (À)-lepadin F, as al ead compound in new antimalarial drug discoveryo wing to its significant antiplasmodiala ctivity but low cytotoxicity, [3] has not been synthesized yet. For the past severaly ears we have been engaged in finding efficient routes toward severalb ioactive alkaloids [16] including (À)-lepadins A-C. [17] Herein, we describe the first synthesis of (À)-lepadin Fthrough astereoselective Diels-Alderr eaction induced by ac hiral lactonedienophile.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of (−)‐Lepadin F based on a Stereoselective Diels–Alder Reaction Controlled by a Ketolactone‐type Dienophile

Jia

et al. 2021

Chemistry A European J

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An efficient approach to the typeIII lepadin alkaloids (lepadins Fa nd G) has been developed throughak ey Diels-Alder reaction, in which an ovel ketolactone-type dienophile with chiral diol unit is employed to generate the desirable all-cis-trisubstituted cyclohexenew ith excellent regio-and stereoselectivity control. The subsequents elective sulfonylationo ft he diol unit followed by S N 2c yclization under hydrogenation conditions could construct the substituted piperidine ring. By using this approach, (À)-lepadin Fi ss ynthesized from ethyl l-lactate for the first time. Figure 1. Structures of lepadins A-I.

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“…However, they may provide a useful tool for studying acetylcholine receptors. A new synthetic approach to (−)-lepadins A–C has been developed based on a stereocontrolled Diels–Alder reaction employing a chiral dienophile [ 172 ].…”

Section: Ascidian Compounds Affecting Signaling Pathwaysmentioning

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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A Stereoselective Approach toward (−)-Lepadins A–C

Cited by 18 publications

References 38 publications

Insights into Cytotoxic Behavior of Lepadins and Structure Elucidation of the New Alkaloid Lepadin L from the Mediterranean Ascidian Clavelina lepadiformis

Insights into Cytotoxic Behavior of Lepadins and Structure Elucidation of the New Alkaloid Lepadin L from the Mediterranean Ascidian Clavelina lepadiformis

Total Synthesis of (−)‐Lepadin F based on a Stereoselective Diels–Alder Reaction Controlled by a Ketolactone‐type Dienophile

Ascidian Toxins with Potential for Drug Development

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