Nonanomeric Spiroketals in Natural Products: Structures, Sources, and Synthetic Strategies

Aho, Jatta E.; Pihko, Petri M.; Rissa, Terhi K.

doi:10.1002/chin.200616267

Cited by 10 publications

(13 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The similar results were obtained when the reaction was carried out in the presence of Lewis acids (for more details, see the Supplementary data). Greater stability of naturally occurring 1 compared to 2, could be a result of stabilization by anomeric effect and the related stereoelectronic effects [15,16].…”

Section: <Insert Scheme 1>mentioning

confidence: 99%

Synthesis and in vitro antitumour activity of crassalactone D, its stereoisomers and novel cinnamic ester derivatives

Kovačević

Popsavin

Benedeković

et al. 2017

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Naturally occurring styryl lactone, crassalactone D (1), unnatural 4-epi-crassalactone D (2), and the corresponding 7-epimers (3 and 4) have been synthesized starting from d-glucose. The key step of the synthesis is a new one-pot sequence that commenced with a Z-selective Wittig olefination of suitably functionalized sugar lactols with a stabilized ylide, (methoxycarbonylmethylene)-triphenylphosphorane, in dry methanol, to afford 1 or 3, in the mixtures with the corresponding 4-epimers (2 or 4, respectively). A number of 6-O-cinnamoyl derivatives of styryl lactones 1-4 have been prepared, bearing electron donating or electron withdrawing functionalities in the C-4 position of cinnamic acid residue. The synthesized products were evaluated for their in vitro antiproliferative activity against selected human tumour cell lines, whereupon very potent cytotoxicities have been recorded in many cases. SAR analysis indicated some important structural features responsible for biological activity, such as stereochemistry at the C-4 and C-7 positions, as well as the nature of a substituent at the C-4 position in the aromatic ring of cinnamoate moiety. Flow cytometry and Western blot analysis data gave insight in the mechanism underlying antiproliferative effects of the synthesized compounds.

show abstract

Section: <Insert Scheme 1>mentioning

confidence: 99%

Synthesis and in vitro antitumour activity of crassalactone D, its stereoisomers and novel cinnamic ester derivatives

Kovačević

Popsavin

Benedeković

et al. 2017

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…The stereoisomers they are the only stereoisomers favoured from two anomeric effects derived from the axial-axial arrangement of the spiro C-O bonds. 25,26,27 The configuration of the major diasteromers 12a,b was supported by the observation of a Nuclear Overhauser Enhancement between the C-2 hydrogen and the C-8 hydrogen. As previously reported on similar spiroketals, the minor diastereomers as mobile phase (MP) at FR 0.8 ml/min.…”

Section: Chemistrymentioning

confidence: 85%

“…Numerous complex natural products containing spiroketals framework have been isolated over the years from marine or terrestrial sources and have shown a wide range of important biological activities. 1,2 Among them, the spongistatins 1 are a family of marine macrolides that display remarkable antitumor activity, 3 integramycin 2 is an HIV-1 intregrase inhibitor, 4 reveromycins 3 are polyketide type antibiotics inhibitors of mitogenic epidermal growth factor (EGF) activity, [5][6][7] tautomycin 4 and okadaic acid 5 are protein phosphatase inhibitors, [8][9][10] spirofungin A 6 selectively inhibits the activity of isoleucyl-tRNA synthetase and displays antiproliferative activity of cancer cells, 11 and the rubromycins that exhibit an array of antimicrobial activity, cytotoxicity and potent ability to inhibit human telomerase ( Figure 1). [12][13][14][15][16]…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Enantiomeric Separation of a Novel Spiroketal Derivative: A Potent Human Telomerase Inhibitor with High in Vitro Anticancer Activity

et al. 2016

View full text Add to dashboard Cite

The synthesis, the enantiomeric separation, and the characterization of new simple spiroketal derivatives have been performed. The synthesized compounds have shown a very high anticancer activity. Cell proliferation assay showed that they induce a remarkable inhibition of cell proliferation in all cell lines treated, depending on culture time and concentration. The compounds have also shown a potent nanomolar human telomerase inhibition activity and apoptosis induction. CD melting experiments demonstrate that spiroketal does not affect the G-quadruplex (G4) thermal stability. Docking studies showed that telomerase inhibition could be determined by a spiroketal interaction with the telomerase enzyme.

show abstract

“…Bicyclic, fused, and spiroketals are present in natural compounds. Various biomedically important non-natural and natural systems possess spiroketals [145][146][147][148]. Most common method for the synthesis of spiroketals is the cyclocondensation of ketone diols among other developed methods [149,150] (Scheme 20).…”

Section: Scheme 17mentioning

confidence: 99%

Gold-catalyzed C–O bond forming reactions for the synthesis of six-membered O-heterocycles

et al. 2019

View full text Add to dashboard Cite

The heterocycles are present in the drugs and pesticides in a major proportion and development of new strategies for the synthesis of these compounds is attractive topic for the synthetic and medicinal chemists. Synthesis of heterocycles is one of the important areas in synthetic organic chemistry. The present manuscript reported the synthesis of six-membered heterocylces with oxygen heteroatom using gold catalysts. This review covered interesting discoveries in the past few years.

show abstract

Nonanomeric Spiroketals in Natural Products: Structures, Sources, and Synthetic Strategies

Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cited by 10 publications

References 1 publication

Synthesis and in vitro antitumour activity of crassalactone D, its stereoisomers and novel cinnamic ester derivatives

Synthesis and in vitro antitumour activity of crassalactone D, its stereoisomers and novel cinnamic ester derivatives

Synthesis and Enantiomeric Separation of a Novel Spiroketal Derivative: A Potent Human Telomerase Inhibitor with High in Vitro Anticancer Activity

Gold-catalyzed C–O bond forming reactions for the synthesis of six-membered O-heterocycles

Contact Info

Product

Resources

About