Synthesis of (3S,4R)-bengamide E

Liu, Qi Jun; Li, Hong; Chen, Shao Peng; Zhou, Guo Chun

doi:10.1016/j.cclet.2010.11.023

Cited by 10 publications

(10 citation statements)

References 12 publications

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“…1e,3,38,42−48 Compounds with single-digit nanomolar or subnanomolar activity against MDA-MB-435 or HCT-116 tumor cell lines represent important inputs for the design of a potential clinical candidate. Alternatively, minor modifications of the polyketide OCH 3 group, changing the absolute configurations at positions C-5 to C-8, or replacing the caprolactam with unoptimized subunits can be disastrous.…”

Section: Structure–activity Relationship Cytotoxicity Activity Pattermentioning

confidence: 99%

The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects

2017

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This review focuses entirely on the natural bengamides and selected synthetic analogues that have inspired decades of research. Bengamide A was first reported in 1986 from the sponge Jaspis cf. coriacea, and bengamide-containing sponges have been gathered from many biogeographic sites. In 2005, a terrestrial Gram-negative bacterium, Myxococcus virescens, was added as a source for bengamides. Biological activity data using varying bengamide-based scaffolds has enabled fine-tuning of structure–activity relationships. Molecular target finding contributed to the creation of a synthetic “lead” compound, LAF389, that was the subject of a phase I anticancer clinical trial. Despite clinical trial termination, the bengamide compound class is still attracting worldwide attention. Future breakthroughs based on the bengamide scaffold are possible and could build on their nanomolar in vitro and positive in vivo antiproliferative and antiangiogenic properties. Bengamide molecular targets include methionine aminopeptidases (MetAP1 and MetAP2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). A mixed PKS/NRPS biosynthetic gene cluster appears to be responsible for creation of the bengamides. This review highlights that the bengamides have driven inspirational studies and that they will remain relevant for future research, even 30 years after the discovery of the first structures.

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Section: Structure–activity Relationship Cytotoxicity Activity Pattermentioning

confidence: 99%

The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects

2017

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“…The comparison of Panel A plots differences in 13 C shifts of natural bengamide E ( 8 ) from J. coriacea 36 versus data published for 8 from three different enantiospecific total syntheses; 40–42 and documents that the variation in shifts at each site is < 1ppm. By contrast, the information of Panel B shows that modification of the absolute configurations at C-6 and C-7 in the synthetic 8 diastereomer of 5 R , 6 R , 7 S , 8 R configuration, also obtained by an enantiospecific total synthesis, 43 imparts a >1 ppm change in the 13 C NMR chemical shifts at the 3/4 sites. Finally, Panel C illustrates the close parallelisms in shifts of the following set: (a) natural bengamide E ( 8 ), synthetic bengamide E ( 8 ), (c) natural bengamide E’( 13 ) as a diastereomeric mixture, and (d) synthetic E’ ( 13 ) reported from a scalemic total synthesis.…”

Section: Resultsmentioning

confidence: 92%

Myxobacteria versus sponge-derived alkaloids: The bengamide family identified as potent immune modulating agents by scrutiny of LC–MS/ELSD libraries

Johnson¹,

Sohn²,

Vaske³

et al. 2012

Bioorganic & Medicinal Chemistry

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A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E’ (13) and F’ (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC Santa Cruz repository allowed expansion of the structure activity relationship (SAR) studies. The activity patterns observed for bengamide A (6), B (7), E (8), F (9), LAF 389 (12) and 13–14 gave rise to the following observations and conclusions. Compounds 6 and 7 display potent inhibition of NF-κB (at 80 and 90 nM respectively) without cytotoxicity to RAW264.7 macrophage immune cells. Western blot and qPCR analysis indicated that 6 and 7 reduce the phosphorylation of IκBα and the LPS-induced expression of the pro-inflammatory cytokines/chemokines TNFα, IL-6 and MCP-1 but do not effect NO production or the expression of iNOS. These results suggest that the bengamides may serve as therapeutic leads for the treatment of diseases involving inflammation, that their anti-tumor activity can in part be attributed to their ability to serve as immune modulating agents, and that their therapeutic potential against cancer merits further consideration.

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“…After the publication of our review about the chemistry and biology of the bengamides and bengazoles in 2014 [1], a new review was published in 2017 by Crews et al [36]. In summary, until 2014, a total of 111 analogues of the bengamides were synthesized [27,[37][38][39][40][41], together with numerous total syntheses of the natural congeners [42][43][44][45][46], by different research groups, and biologically evaluated against different tumor cell lines, which, overall, represents an extensive and thorough structure-activity relationship study that has allowed for the establishment of a consistent and well-defined pharmacophore for the bengamides, summarized in the following points: (a) the importance of the substituent at the terminal olefinic position; (b) the essential role of the polyketide fragment, whose hydroxyl groups and stereochemistries are essential for their biological properties; and; (c) the beneficial impact of the modification of the caprolactam fragment in their antitumor properties. Among the analogues that displayed improved pharmacological properties in comparison with the natural counterparts, were the bengamide A analogue 25, known as LAF389, which presented a greater solubility in water with respect to bengamide A (1), or the modified caprolactam analogue 26, the cyclopentyl analogue of bengamide E 27, or the ring-opened bengamide analogue 28, which exhibited a major antitumor potency compared with bengamide E (5), being analogue 28 the most potent analogue identified so far (Figure 3).…”

Section: New Progress In Antitumor Properties Of the Bengamidesmentioning

confidence: 99%

The Development of the Bengamides as New Antibiotics against Drug-Resistant Bacteria

et al. 2022

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The bengamides comprise an interesting family of natural products isolated from sponges belonging to the prolific Jaspidae family. Their outstanding antitumor properties, coupled with their unique mechanism of action and unprecedented molecular structures, have prompted an intense research activity directed towards their total syntheses, analogue design, and biological evaluations for their development as new anticancer agents. Together with these biological studies in cancer research, in recent years, the bengamides have been identified as potential antibiotics by their impressive biological activities against various drug-resistant bacteria such as Mycobacterium tuberculosis and Staphylococcus aureus. This review reports on the new advances in the chemistry and biology of the bengamides during the last years, paying special attention to their development as promising new antibiotics. Thus, the evolution of the bengamides from their initial exploration as antitumor agents up to their current status as antibiotics is described in detail, highlighting the manifold value of these marine natural products as valid hits in medicinal chemistry.

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Synthesis of (3S,4R)-bengamide E

Cited by 10 publications

References 12 publications

The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects

The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects

Myxobacteria versus sponge-derived alkaloids: The bengamide family identified as potent immune modulating agents by scrutiny of LC–MS/ELSD libraries

The Development of the Bengamides as New Antibiotics against Drug-Resistant Bacteria

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