Total Synthesis of the Antitumor Macrolides, (+)-Brefeldin A and 4-Epi-Brefeldin A from <scp>d</scp>-Glucose: Use of the Padwa Anionic Allenylsulfone [3 + 2]-Cycloadditive Elimination To Construct Trans-Configured Chiral Cyclopentane Systems

Xiong, Ziyue; Hale, Karl J.

doi:10.1021/acs.orglett.6b02002

Cited by 16 publications

(14 citation statements)

References 46 publications

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“…As per LC-MS results, we observed 2 peaks in the chromatogram (Figure 5(a)), a smaller peak at retention time of 4.14 min and a larger peak at the retention time of 6.78 min. The mass spectrum of this peak showed the presence of a fragment ion with 100 % abundance with a mass to charge ratio of 437.4 (Figure 5(b)), with a base peak value of 453.2, which corresponds to the molecular weight of brefeldin A. brefeldin A is an anticancer compound as per earlier reports [12] and is listed in the cancer resource database (http://dataanalysis.charite.de/care). Cancer is a global challenge with higher number of cases and deaths reported annually around the world.…”

Section: Lc-ms Analysismentioning

confidence: 78%

Decreased S Phase and G2/M Phase Cells by a Bioactive Fraction from the Hexane Extract of Rhododendron aroboreum Leading to the Apoptosis of HeLa Cells In-Vitro

Timsina

Nadumane²

2022

Trends Sci

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Search for novel anticancer compounds from natural sources is a priority goal of cancer biologists. Rhododendron arboreum is one of the most stately and impressive Rhododendron species. In hilly areas, the flowers of R. arboreum are used for the treatment of chronic diseases. The current study was aimed to evaluate the anti-proliferative property of R. arboreum on HeLa cells. Crude extract of the flower was prepared using serial extraction procedure with different solvents. Cytotoxicity of the extracts on HeLa, CHO and human lymphocytes were assessed using MTT assay and trypan blue dye exclusion methods. The extract was further purified by TLC and characterized by LC-MS method. The hexane extract showed significant cytotoxicity to HeLa cells. This extract was fractionated using thin layer chromatography, 6 fractions were isolated, out of which fraction 3 showed the maximum cytotoxic activity with an IC50 of 15 μg/mL. The mechanism of action was observed as apoptosis induction as indicated by elevated caspase activity and inhibition of cell cycle with reduced cell population in the S and G2/M phases. LC-MS analysis of this promising bioactive fraction resulted in a molecular ion fragment with an m/z value of 437.48 which is corresponding to that of brefeldin A, an anticancer compound. It can be concluded that R. arboreum flower has cytotoxic activity which could be due to the presence of brefeldin A, that warrants further studies on purification and characterization towards the development of highly efficient therapeutics for cancer. HIGHLIGHTS Anti-cancer drug discovery from natural sources like medicinal herbs having diverse metabolites of therapeutic significance provide lead molecules towards cancer drug development The anti-proliferative/apoptotic potential of a bioactive fraction from Rhododendron aroboreum, was analysed on cancer cell lines by MTT, Lactate dehydrogenase, Caspase and cell cycle studies. The bioactive compound was characterized through preparative TLC and LC-MS methods The potent apoptotic potential of Rhododendron aroboreum flower extract was demonstrated through reduced S-phase and G2/M phase cells, increased caspase, LDH activities in our study results The presence of Brefeldin A, previously reported as an anticancer compound in a microbe, was observed for the 1st time in Rhododendron aroboreum through our study in LC-MS analysis GRAPHICAL ABSTRACT

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Section: Lc-ms Analysismentioning

confidence: 78%

Decreased S Phase and G2/M Phase Cells by a Bioactive Fraction from the Hexane Extract of Rhododendron aroboreum Leading to the Apoptosis of HeLa Cells In-Vitro

Timsina

Nadumane²

2022

Trends Sci

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“…A recent synthetic study employing a [3+2]-cycloaddition route was reported to enable a versatile synthesis of BFA 1 and 4-epi-BFA 12 from BFA, in a unified strategy [ 37 ]. In Scheme 23 , cycloaddition of unsaturated enone 110 with allenylsulfone 111 afforded cyclopentane 112 in a stereoselective manner.…”

Section: Resultsmentioning

confidence: 99%

Recent Synthesis and Discovery of Brefeldin A Analogs

Paek

2018

Marine Drugs

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The recent development of analogs of brefeldin A (BFA), a fungal metabolite, for the improvement of BFA apoptosis-inducing activity is described. BFA has been isolated from various soil or, more recently, marine fungi and has shown versatile beneficial activities. More importantly, the apoptosis-inducing activity of BFA in cancer cells highlights the possibility of further developing this natural product as an anticancer agent. Besides its biological importance, its structural features have also gathered tremendous interest from both medicinal and synthetic chemists. By a medicinal chemistry and total synthesis approach, numerous analogs from BFA have been developed to improve its inferior bioavailability and its antiproliferative ability. In this review, the recent medicinal chemistry efforts in relation to the production of BFA analogs are extensively presented.

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“…A new synthetic approach towards (+)-Brefeldin A 77 was reported by Hale et al [32] The aldehyde 73 was reacted with functionalized sulfone 74 via Julia-Kocienski coupling to produce an intermediate product 75 with E -stereochemistry with 68 % yield. This was transformed into 76 and 77 (Scheme 13) through a sequence of chemical reactions includ-ing deprotection of the PMP ether, hydrolysis of ester group, Yamaguchi macrolactonization, desilylation, etc.…”

Section: Chemistryselectmentioning

confidence: 99%

Recent Applications and Trends in the Julia‐Kocienski Olefination

Rinu¹,

Radhika²,

Anilkumar³

2022

ChemistrySelect

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The Julia-Kocienski (J-K) olefination is a modified version of Julia-Lythgoe olefination. In this reaction, an aldehyde or ketone is coupled with heterocycle-bearing sulfone in the presence of a strong base to yield alkene. It has shown wide application in the synthesis of olefinic fragments in natural product synthesis. The Julia-Kocienski olefination is one of the most efficient protocols for the synthesis of E-alkenes. Nowa-days, a variety of natural products were synthesised by using the Julia-Kocienski olefination as the key step, and several developments and modifications were witnessed in this area. This review comprehends the recent developments and achievements in Julia-Kocienski olefination along with its application in natural product synthesis covering literature from 2016 to 2021.

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Total Synthesis of the Antitumor Macrolides, (+)-Brefeldin A and 4-Epi-Brefeldin A from d-Glucose: Use of the Padwa Anionic Allenylsulfone [3 + 2]-Cycloadditive Elimination To Construct Trans-Configured Chiral Cyclopentane Systems

Cited by 16 publications

References 46 publications

Decreased S Phase and G2/M Phase Cells by a Bioactive Fraction from the Hexane Extract of Rhododendron aroboreum Leading to the Apoptosis of HeLa Cells In-Vitro

Decreased S Phase and G2/M Phase Cells by a Bioactive Fraction from the Hexane Extract of Rhododendron aroboreum Leading to the Apoptosis of HeLa Cells In-Vitro

Recent Synthesis and Discovery of Brefeldin A Analogs

Recent Applications and Trends in the Julia‐Kocienski Olefination

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