Total Synthesis of (±)‐Symbioimine

Varseev, Georgy N.; Maier, Martin E.

doi:10.1002/ange.200601418

Cited by 11 publications

(10 citation statements)

References 35 publications

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“…After methoxymethyl ether (MOM) protection, catalytic hydrogenation removed the triple bond and the benzyl ether to provide primary alcohol 26. By means of Mitsunobu substitution with 1-phenyl-1H-tetrazole-5-thiol (27) and subsequent oxidation of thioether 28, sulfone 29 could be secured on a gram scale.…”

Section: Resultsmentioning

confidence: 99%

Probing the Influence of an Allylic Methyl Group in Zearalenone Analogues on Binding to Hsp90

Rink

Sasse

Zubrienė³

et al. 2010

Chemistry A European J

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By the replacement of an acetate with propionate by means of organic synthesis, a range of zearalenone analogues were prepared that feature an allylic methyl group. For the synthesis of the aliphatic region of the analogues, we used an asymmetric alkylation to yield pentenol derivatives 16 and ent-16. By means of hydroboration the corresponding aldehydes were secured. These were coupled with 2-pentynol derivate 23 by means of a Carreira acetylide addition. Further routine steps led to the sulfones 29 and 45, respectively. After merging them with 2-bromobenzaldehyde 9 in a Julia-Kocienski reaction, metalation, carboxylation, and protecting-group manipulations gave the seco acids 35 and 49. By means of lactonization under Mitsunobu (alcohol activation) or Trost-Kita conditions (carboxyl activation), all four possible macrocyclic ketone stereoisomers were accessible. In all, considering various protecting-group decorations, 16 analogues were obtained and tested for cytotoxicity (L929 mouse fibroblast cell line). Whereas most of the analogues were less active than zearalenone (IC(50)=9.4 μM), the resorcinol derivatives were comparable, with one stereoisomer (40 b) being slightly more active (IC(50)=6.6 μM). These results were also reflected in the binding assays to Hsp90 in which 40 b showed a dissociation constant (K(d)) value of 130 nM.

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Section: Resultsmentioning

confidence: 99%

Probing the Influence of an Allylic Methyl Group in Zearalenone Analogues on Binding to Hsp90

Rink

Sasse

Zubrienė³

et al. 2010

Chemistry A European J

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“…We have not clarified the reason for this trend in stereoselectivity, but the stereoelectronic effect induced by the allylic substituent play a role 4b. 9…”

Section: Methodsmentioning

confidence: 95%

Total Synthesis of (−)‐FR182877 through Tandem IMDA–IMHDA Reactions and Stereoselective Transition‐Metal‐Mediated Transformations

et al. 2009

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A research group at the Fujisawa (now, Astellas) Pharmaceutical Company isolated (À)-FR182877 [1a-d] and its congener, (À)-FR182876 [1e] , from Streptomyces sp. no. 9885. (À)-FR182877 binds and stabilizes microtubules, exhibiting potent cytotoxic activity toward a number of human cancer cell lines with a potency comparable to that of Taxol.[1] The in vivo assay of (À)-FR182877 using mouse models revealed its promising antitumor activity, [1c] suggesting its potency as a lead compound for chemotherapeutic agents. (À)-FR182877 features a unique hexacyclic structure with twelve contiguous stereogenic centers and a reactive "push-pull" alkene [1c] distorted by the ethylene bridge. Its remarkable biological profile and unprecedented structural features has made (À)-FR182877 an attractive compound for total synthesis [2][3][4][5] as well as chemical biology studies. [6] The groups led by Sorensen [2] and Evans [3] have independently reported elegant asymmetric total syntheses of (À)-FR182877 through closely related strategies, involving consecutive transannular cycloadditions. Our interests in the total synthesis of this complex architecture and the recently disclosed unique mode of action of this compound [6c] have prompted us to report herein an alternate synthetic approach to (À)-FR182877.The stereoselective syntheses of the AB-ring and the CD-ring moieties were accomplished by the intramolecular Diels-Alder (IMDA) reaction and the intramolecular heteroDiels-Alder (IMHDA) reaction, [4c,d] respectively. We surmised that these cycloadditions could be sequential; that is, the one-pot tandem IMDA-IMHDA reaction of the acyclic substrate 2 (Scheme 1) could provide the tetracyclic comScheme 1. Synthesis of 6 by the tandem IMDA-IMHDA reaction: a) TESCl, imidazole, CH 2 Cl 2 , RT, 30 min; b) K 2 CO 3 , MeOH, RT, 30 min, 75 % (2 steps); c) MnO 2 , toluene, 80 8C, 2 d, 28 %; d) PPTS (cat.), MeOH, RT, 1.5 h, 82 %; e) Dess-Martin periodinane, NaHCO 3 , CH 2 Cl 2 , RT, 30 min, 89 %; f) BH 3 ·THF, THF, À20 8C, 30 min, 75 %, (24:1 d.r.); g) TBSOTf, Et 3 N, CH 2 Cl 2 , RT, 2 h, 94 %. PPTS = pyridinium p-toluenesulfonate, TBS = tert-butyldimethylsilyl, TES = triethylsilyl, Tf = trifluoromethanesulfonyl, TIPS = triisopropylsilyl.

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“…Since the discovery of platencin was published in 2007, a number of total or formal syntheses of this molecule have been reported. [8] Recently, Maier and co-workers [8k] reported a practical route to platencin using an oxygen-mediated palladium catalyzed cycloalkenylation reaction as the key step. Some relevance to this work has prompted us to disclose our preliminary results for the synthesis of platencin.…”

Section: Antibiotic Synthesismentioning

confidence: 99%

“…Synthesis of platencin core 14 constitutes a formal synthesis of platencin as this carbon skeleton has been converted to platencin previously. [8g] Our synthesis features 8 steps with an unoptimized overall yield of 19% (21% based on recovered diketone 5 ) using commercially available starting material 7 .…”

Section: Antibiotic Synthesismentioning

confidence: 99%

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A Symmetry‐Based Concise Formal Synthesis of Platencin, a Novel Lead against “Superbugs”

Ghosh

2009

Angew Chem Int Ed

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Total Synthesis of (±)‐Symbioimine

Cited by 11 publications

References 35 publications

Probing the Influence of an Allylic Methyl Group in Zearalenone Analogues on Binding to Hsp90

Probing the Influence of an Allylic Methyl Group in Zearalenone Analogues on Binding to Hsp90

Total Synthesis of (−)‐FR182877 through Tandem IMDA–IMHDA Reactions and Stereoselective Transition‐Metal‐Mediated Transformations

A Symmetry‐Based Concise Formal Synthesis of Platencin, a Novel Lead against “Superbugs”

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