Oxidative Coupling as a Biomimetic Approach to the Synthesis of Scytonemin

Ekebergh, Andreas; Karlsson, Isabella; Mete, Rudi; Ye, Pan; Börje, Anna; Mårtensson, Jerker

doi:10.1021/ol201812n

Cited by 37 publications

(27 citation statements)

References 21 publications

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“…After being stirred for 5 h, the mixture was quenched by addition of saturated aqueous NH 4 Cl and extracted with hexane. The extract was washed with water and brine, dried and concentrated to dryness.…”

Section: -Bromo-2-[2-(trimethylsilyl)ethynyl]-benzene (11)mentioning

confidence: 99%

“…To a solution of the residue in THF (50 mL) were added PdCl 2 (PPh 3 ) 2 (109 mg, 0.16 mmol), CuI (15 mg, 0.078 mmol), propargyl alcohol (0.70 mL, 12 mmol) and iPr 2 NH (7.7 mL, 55 mmol) at room temperature. After being stirred for 25 h, the mixture was quenched by addition of saturated aqueous NH 4 Cl, and extracted with AcOEt. The extract was washed with water and brine, dried and concentrated to dryness.…”

Section: -[2-(2-(trimethylsilyl)ethynyl)phenyl]-2-propyn-1-ol (13)mentioning

confidence: 99%

“…2,3) In 2011, Mårtensson and colleagues achieved the first total synthesis of scytonemin by taking advantage of the tandem Heck carbocyclization/Suzuki-Miyaura coupling and a bioinspired oxidative dimerization. 4) Of particular interest is its interesting biological features. Scytonemin is a UVabsorbing pigment that protects important cellular components in a cyanobacteria against harmful UV radiation.…”

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confidence: 99%

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Synthesis of a Carbon Analogue of Scytonemin

Mukai

Arima

Hirata

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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The synthesis of a carbon analogue of scytonemin was accomplished on the basis of molybdenummediated intramolecular double Pauson-Khand type reaction of bis(allenyne), followed by the double aldol condensation of the formed double Pauson-Khand type adduct.Key words scytonemin; allene; [2+2+1] cycloaddition; alkyne; molybdenum; aldol condensation Scytonemin (1) is the cyanobacterial dimeric alkaloid pigment, whose chemical structure has been elucidated by Gerwick and co-workers in 1993, 1) over 100 years after its discovery. Scytonemin has an intriguing novel structural feature, which consists of a two 1,1′-linked cyclopent [b] indole-2(1H)-one framework possessing 4-hydroxybenzylidenes at the 3-positions of the fused tricyclic systems. The biosynthetic studies of scytonemin have been recently made by Walsh and Balskus.2,3) In 2011, Mårtensson and colleagues achieved the first total synthesis of scytonemin by taking advantage of the tandem Heck carbocyclization/Suzuki-Miyaura coupling and a bioinspired oxidative dimerization. 4) Of particular interest is its interesting biological features. Scytonemin is a UVabsorbing pigment that protects important cellular components in a cyanobacteria against harmful UV radiation. [5][6][7][8] Besides this important function, scytonemin exhibits a biological activity as a small molecule inhibitor of polo-like kinase 1 9) and possesses anti-inflammatory and antiproliferative properties. 10)During our studies on the syntheses of various kind of alkaloids, [11][12][13][14][15][16][17][18][19] we became very interested in the highly conjugated and characteristic dimeric structure of scytonemin as well as its biological activity. We postulated that the origin of the biological activity of scytonemin (1) might be elucidated by comparison with its carbon analogue, in which two nitrogen atoms are replaced by two carbon atoms. Therefore, our endeavor was directed toward the synthesis of 2, a carbon analogue of scytonemin (1) (Chart 1).In 2005, Liu and Datta developed the efficient synthesis of 1H-cyclopent[a] inden-2-one (4a) from 1-ethynyl-2-(1,2-propadienyl) benzene (3a) through the Mo(CO) 3 (MeCN) 3 -mediated carbonylative [2+2+1] ring-closing reaction at 25°C in a stoichiometric manner 20) (Chart 2). They also reported the catalytic version of that transformation in the presence of 5 mol% of [RhCl(CO) 2 ] 2 at 90°C to furnish 4a in 62% yield along with the by-production of 2-methylnaphthalene (5), the latter of which should be arisen from the MyersSaito cycloaromatization 21-25) of 3a. We have independently reported that treatment of 3-(2-ethynylphenyl) prop-2-ynyl benzenesulfinate (6) with 2.5 mol% of [RhCl(CO) 2 ] 2 at 40°C in an atmosphere of CO effected the successive 2,3-sigmatropic rearrangement and carbonylative [2+2+1] ring-closing reaction of the resulting allenyne species 3b to afford the 8-(phenylsulfonyl)-1H-cyclopent[a] inden-2-one (4b) in a high yield.26) In this case, the formation of 2-methylnaphthalene could not be detected in the reaction mixture. We now report t...

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Section: -Bromo-2-[2-(trimethylsilyl)ethynyl]-benzene (11)mentioning

confidence: 99%

Section: -[2-(2-(trimethylsilyl)ethynyl)phenyl]-2-propyn-1-ol (13)mentioning

confidence: 99%

mentioning

confidence: 99%

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Synthesis of a Carbon Analogue of Scytonemin

Mukai

Arima

Hirata

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Recently, by using oxidative coupling as a biomimetic approach, the total chemical synthesis of scytonemin has been achieved (Ekebergh et al 2011). The downstream region is involved in aromatic amino acid biosynthesis.…”

Section: Biosynthesis Of Scytoneminmentioning

confidence: 99%

Emerging applications of cyanobacterial ultraviolet protecting compound scytonemin

Mishra¹,

Tandon

Kesarwani

et al. 2014

J Appl Phycol

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Cyanobacteria are one of the most ancient life forms present today. This phylum of organisms is capable of photosynthesis, and they depend on solar radiation for their survival. They are found under diverse climatic conditions where ultraviolet (UV) radiation can damage cellular machinery. In order to be protected from harmful radiation, many cyanobacteria produce the UV radiation-absorbing compound, scytonemin in the extracellular sheath. In this review, characteristic features of seven sheath-forming cyanobacteria are shown and genes involved in scytonemin biosynthesis are discussed. Scytonemin as a sunscreen compound and its biomedical applications are also summarized. Recent advances on the application of scytonemin as a biosignature for extraterrestrial life on Mars are also discussed.

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“…[ xl ] Inspired by the biosynthetic studies by Balskus and Walsh, [xli] Mårtensson and coworkers prepared ketone 75 in seven steps from 3-indole acetic acid and showed that dimer 76 is readily generated when the lithium enolate of 75 is treated with FeCl 3 (Scheme 7). [xlii] The diastereoselectivity of this coupling was inconsequential; after cleavage of the methyl ethers with BBr 3 , DDQ-mediated oxidation afforded the natural product 77 (28% over two steps from 76 ).…”

Section: Natural Product Synthesismentioning

confidence: 99%

Oxidative Coupling of Enolates, Enol Silanes, and Enamines: Methods and Natural Product Synthesis

2012

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The oxidative coupling of enolates, enol silanes, and enamines provides a direct method for the construction of useful 1,4-dicarbonyl synthons. Despite being first reported in 1935, with subsequent important advances beginning in the 1970’s, the development of this powerful reaction into a reliable methodology was somewhat limited. In recent years, there have been a number of reports from several research groups demonstrating advances in several neglected areas of oxidative coupling. This microreview summarizes these new advances in methodology and provides an overview of recent natural product syntheses that showcase the power of these transformations.

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Oxidative Coupling as a Biomimetic Approach to the Synthesis of Scytonemin

Cited by 37 publications

References 21 publications

Synthesis of a Carbon Analogue of Scytonemin

Synthesis of a Carbon Analogue of Scytonemin

Emerging applications of cyanobacterial ultraviolet protecting compound scytonemin

Oxidative Coupling of Enolates, Enol Silanes, and Enamines: Methods and Natural Product Synthesis

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