Syntheses and Biological Properties of Brefeldin Analogues

Förster, Sebastian; Persch, Elke; Tverskoy, Olena; Röminger, Frank; Helmchen, Günter; Klein, Christian D.; Gönen, Basak; Brügger, Britta

doi:10.1002/ejoc.201001297

Cited by 23 publications

(8 citation statements)

References 61 publications

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“…Amino-BFA analog 57 was prepared using reductive amination of 7-keto BFA 8 and chiral sulfinyl amine 55 , followed by acidic deprotection [ 26 ], as shown in Scheme 13 . However, when 57 was used to treat HeLa cells to observe its disrupting effect on the Golgi complex, it showed less activity than BFA itself.…”

Section: Resultsmentioning

confidence: 99%

“…Instead of hydrogenation, dihydroxylation of cyclopentene 79 was carried out to introduce a hydroxyl group at the C6 position [ 26 ], as shown in Scheme 18 . Two substituents of cis- 79 possessed a β-face of the cyclopentene plane, and directed catalysis of potassium osmate occurred on the α-face dominantly.…”

Section: Resultsmentioning

confidence: 99%

“…Helmchen group also reported the semi-synthesis of BFA analogs using hybridization of a BFA skeleton and artificial side chains [ 26 ], as shown in Scheme 19 . Starting from BFA, protection and chemoselective olefin cleavage of the electron-rich olefin were tried to obtain properly substituted cyclopentanyl aldehyde 90 in a large scale.…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Recent Synthesis and Discovery of Brefeldin A Analogs

Paek

2018

Marine Drugs

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“…170 Syntheses of various brefeldin analogs have been carried out and their biological properties have been studied by Helmchen and co-workers. 171 The diastereoselective reductive amination methodology reported by Ellman and co-workers discussed earlier has been successfully employed to synthesize (7S)-amino-BFC from 7-dehydro-BFA. The substrate was treated with tert-butyl sulfinamide and Ti(OEt) 4 in THF in a refluxing condition.…”

Section: Total Synthesis Of Madindolinesmentioning

confidence: 99%

Asymmetric Hydroamination and Reductive Amination in Total Synthesis

Ghorai

Tiwari

Bhattacharyya

2013

Stereoselective Synthesis of Drugs and Natural Products

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Asymmetric hydroamination (AHA) and asymmetric reductive amination (ARA) are one of the most popular strategies for enantioselective synthesis of chiral amines, which are very important from a synthetic and a biological point of view. The addition of the NH bond across an unsaturated CC bond is known as hydroamination. AHA is ideal for industrial processes as it is a 100% atom‐economic reaction and involves readily available substrates. For broadening its scope for a variety of substrates, many metal‐based as well as metal‐free catalytic systems have been developed for asymmetric hydroamination. Along with the synthesis of functionalized chiral amines, AHA has served as a key strategy in the synthesis of the core of various natural products like codeine, pseudodistomin, swainsonine and of drugs like pentazocine. Reductive amination is a widely used efficient synthetic protocol to install an amine group in place of a carbonyl group in an organic compound. The reaction proceeds through the formation of imine and subsequent one‐pot reduction of it to give the product amine. Use of a metal‐chiral ligand combination, chiral Brønsted acid or chiral organocatalyst, or chiral auxiliary in the reaction can give rise to chiral amine products that are often valuable synthetic intermediates en route to many drugs and natural products. Application of these protocols in the total synthesis of drugs and natural products will be discussed along with some experimental procedures.

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“…(+)-Brefeldin A has elicited considerable medicinal interest over the years, due to the fact that its water-soluble 7- N , N -dimethylglycinate pro-drug, breflate, was reported to be a powerful inhibitor of human melanoma xenograft growth in mice . Despite these early exciting findings, subsequent more detailed pharmacological evaluation of breflate and other brefeldin A pro-drugs at higher dosages (20 mg/kg) did eventually reveal that they could bring about seizures in mice and cause noticeable neurodegeneration .…”

mentioning

confidence: 99%

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

Xiong

Hale

2016

Org. Lett.

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A new synthesis of (+)-brefeldin A is reported via Padwa allenylsulfone [3 + 2]-cycloadditive elimination. Cycloadduct 13 was initially elaborated into iodide 27, which, following treatment with Zn, gave aldehyde 28 whose C(9) stereocenter was epimerized. Further elaboration into enoate 38 and Julia-Kocienski olefination with 5 subsequently afforded 39, which was deprotected at C(1) and O(15). Yamaguchi macrolactonization of the seco-acid thereafter afforded a macrocycle that underwent O-desilylation and inversion at C(4) to give (+)-brefeldin A following deprotection.

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Syntheses and Biological Properties of Brefeldin Analogues

Cited by 23 publications

References 61 publications

Recent Synthesis and Discovery of Brefeldin A Analogs

Recent Synthesis and Discovery of Brefeldin A Analogs

Asymmetric Hydroamination and Reductive Amination in Total Synthesis

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

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