Studies toward the Synthesis of Smenamide A, an Antiproliferative Metabolite from Smenospongia aurea: Total Synthesis of ent-Smenamide A and 16-epi-Smenamide A

Caso, Alessia; Mangoni, Alfonso; Piccialli, Gennaro; Costantino, Valeria; Piccialli, Vincenzo

doi:10.1021/acsomega.7b00095

Cited by 21 publications

(28 citation statements)

References 37 publications

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“…Thus, the activation of 2,4-dimethyl-2-pentenoic acid as the pentafluorophenylester ( 16 ) ( Figure 3 ) and its subsequent coupling with the previously synthesized pyrrolinone subunit 17 [ 8 ], afforded compound 8 in an 85% yield.…”

Section: Resultsmentioning

confidence: 99%

“…It is worth stating that the configuration at C-16 in both smenamides remained unassigned in the original study due to the limited amount of the natural substances available. In a recent study, a chiral protocol strategy aimed at the total synthesis of the smenamide family was designed, starting from commercially available S -citronellene, a cheap starting material [ 8 ]. Two stereoisomers of smenamide A, namely ent -smenamide A and 16- epi -smenamide A ( 7 , Figure 2 ), were synthesized.…”

Section: Introductionmentioning

confidence: 99%

“…MM is a clonal plasma cell malignancy accounting for approximately 13% of all hematological cancers [ 9 ]. It originates from post-germinal centre B cells that accumulate somatic hypermutation and immunoglobulin heavy-chain class switching [ 8 ]. Several novel agents have been introduced into clinical practice but, after an initial response, most patients relapse or progress with a treatment-refractory disease [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Smenamide A Analogues. Synthesis and Biological Activity on Multiple Myeloma Cells

et al. 2018

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Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active, while compound 13, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Smenamide A Analogues. Synthesis and Biological Activity on Multiple Myeloma Cells

et al. 2018

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“…Although the cytotoxic activity of smenamide A could be determined with only a few micrograms of compound, larger amounts were needed to further study the biological activity and to determine the configuration at C-16, which remained undetermined until the total synthesis of 16-epi-smenamide A and ent-smenamide A was accomplished [8]. To further our understanding of the activity-related structural features of this class of molecules, a series of short derivatives of the 16-epi-series were designed, prepared, and tested for antiproliferative activity [9].…”

Section: Of 12mentioning

confidence: 99%

Fast Detection of Two Smenamide Family-Members Using Molecular Networking

Caso¹,

Esposito²,

Sala³

et al. 2019

Preprint

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Caribbean sponges of the genus Smenospongia are a prolific source of chlorinated secondary metabolites. The use of molecular networking as a powerful dereplication tool revealed the presence in the metabolome of S. aurea of two new members of the smenamide family, namely smenamide F (1) and G (2). The structure of smenamide F (1) and G (2) was determined by spectroscopic analysis (NMR, MS, ECD). The relative and the absolute configuration at C-13, C-15, and C-16 was determined on the basis of the conformational rigidity of a 1,3-disubstituted alkyl chain system (i.e. the C-12/C-18 segment of compound 1). Smenamide F (1) and G (2) were shown to exert a selective moderate antiproliferative activity against cancer cell lines MCF-7 and MDA-MB-231, while being inactive against MG-63.

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“…The Caribbean sponges of the genus Smenospongia have been previously shown to contain a wide array of chlorinated metabolites deriving from the PKS-NRPS pathway, such as smenamides, conulothiazoles, and smenothiazoles [ 11 ]. They have been used as guiding structures in our anticancer drug discovery programs [12,13].…”

Section: Introductionmentioning

confidence: 99%

Isolation of Smenopyrone, a Bis-g-Pyrone Polypropionate from the Caribbean Sponge Smenospongia Aurea.

Esposito¹,

Teta²,

Sala³

et al. 2018

Preprint

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The organic extract of the Caribbean sponge Smenospongia aurea has been shown to contain an array of novel chlorinated secondary metabolites derived from a mixed PKS-NRPS biogenetic route, such as the smenamides. Here we report the presence of a biogenetically different compound, smenopyrone (1), a polypropionate containing two -pyrone rings. The structure of smenopyrone, including its relative and absolute stereochemistry, was determined by spectroscopic analysis (NMR, MS, ECD) supported by comparison with model compounds from the literature. Pyrone polypropionates are unprecedented in marine sponges, but are commonly found in marine mollusks, where their biosynthesis by symbiotic bacteria has been hypothesized and at least in one case demonstrated. As pyrones have recently been recognized as bacterial signaling molecules, we speculate that smenopyrone could mediate inter-kingdom chemical communication between S. aurea and its symbiotic bacteria.

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Studies toward the Synthesis of Smenamide A, an Antiproliferative Metabolite from Smenospongia aurea: Total Synthesis of ent-Smenamide A and 16-epi-Smenamide A

Cited by 21 publications

References 37 publications

Smenamide A Analogues. Synthesis and Biological Activity on Multiple Myeloma Cells

Smenamide A Analogues. Synthesis and Biological Activity on Multiple Myeloma Cells

Fast Detection of Two Smenamide Family-Members Using Molecular Networking

Isolation of Smenopyrone, a Bis-g-Pyrone Polypropionate from the Caribbean Sponge <em>Smenospongia Aurea</em>.

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