Asymmetric Total Synthesis of Dibenzocyclooctadiene Lignan Natural Products

Coleman, Robert S.; Gurrala, S. R.; Mitra, Soumya; Raao, Amresh

doi:10.1021/jo051525i

Cited by 30 publications

(23 citation statements)

References 92 publications

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“…Intramolecular couplings were used in synthesis of isocomplestatin [244] and biphenomycin B [245]. (11) Alkyl boron reagents were used in synthesis of for example minfiensine [246], zoapatanol [247], dibenzocyclooctadiene lignans [248,249], the C1-C25 fragment of amphidinol 3 [250], (+)-SCH-351448 [251], the C10-C24 fragment of inostamycins [252], (+)-brefeldin C [253], (+)-wortmannin [254], cordiaquinone J and K [255] and cannabinoid antagonists [256].…”

Section: Carbon-carbon Bond-forming Reactions Via Transmetallationmentioning

confidence: 99%

“…Copper mediated an intramolecular coupling of two aryl bromides in a synthesis of dibenzocyclooctadiene lignans (Eq. (26)) [249,250].…”

Section: Carbon-carbon Bond-forming Reactions Using Terminal Alkynes mentioning

confidence: 99%

“…Rhodium catalyzed an allylic alkylation-[5 + 2]cycloaddition or a cycloisomerization sequence (Eqs. (249) and (250)) [1000]. Rhenium catalyzed the formation of indenes from aromatic aldimines and alkynes (Eq.…”

Section: Cycloadditionsmentioning

confidence: 99%

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Transition metals in organic synthesis: Highlights for the year 2005

Söderberg

2008

Coordination Chemistry Reviews

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Section: Carbon-carbon Bond-forming Reactions Via Transmetallationmentioning

confidence: 99%

“…Copper mediated an intramolecular coupling of two aryl bromides in a synthesis of dibenzocyclooctadiene lignans (Eq. (26)) [249,250].…”

Section: Carbon-carbon Bond-forming Reactions Using Terminal Alkynes mentioning

confidence: 99%

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Transition metals in organic synthesis: Highlights for the year 2005

Söderberg

2008

Coordination Chemistry Reviews

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“…To form the axially chiral biaryl system, various strategies have been devised. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Homocoupling of aryl halides bearing a chiral oxazoline moiety by the Ullmann reaction has been used to synthesize unsymmetrical biaryls. [25][26][27][28] One of the two diastereomers of a C 2 -symmetrical chiral bisoxazoline may be obtained by the combination between the ligand and a metal ion.…”

Section: Introductionmentioning

confidence: 99%

Absolute configurations and CD spectra of axially chiral biphenyls prepared in a facile manner by crystallization‐induced configuration transformation

et al. 2010

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Axially chiral biphenyls such as (M,S)-3k have been conveniently obtained by crystallization of their diastereomeric mixtures, which were synthesized from racemic 4,4'-dimethoxy-5,6,5',6'-bis(methylenedioxy)-2-carboxylester-2'-carboxyl-biphenyls 4 and chiral amino alcohols (R)-alaninol, (S)-alaninol, (S)-valinol, and (S)-phenylalaninol. A crystallization-induced configuration transformation of the biphenyls was thus achieved. It was found that amide formation of an (S)-valinol or (S)-phenylalaninol at the 2'-position of the biphenyl usually induced the deposition of crystals with the (M)-configuration from ethanol in yields higher than 50%. The absolute configurations (ACs) of two crystalline biphenyls have been determined by X-ray crystallographic analysis. The ACs of nine biphenyls have been assigned based on their CD spectra. Further, stability investigation of these axially chiral biphenyls revealed that the ACs could revert upon redissolution. The energy barrier to epimerization between (P,R)-3b and (M,R)-3b was measured as DeltaG(#) = 21.45 kcal/mol and the half-life in ethanol at 301 K was 17.1 h.

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“…However, because natural lignans with multiple chiral centers are not always ideal as drug candidates, even though many total synthesis studies have been reported,13 we were prompted to use lignans as leads for new compounds with simpler, more accessible structures. The biphenyl moiety in natural dibenzocyclooctadiene lignans is substituted with methoxy and methylenedioxy groups at different positions, resulting in either symmetrical (wuweizi C) or unsymmetrical (wuweizi B) biphenyls, as shown in Figure 1, and this feature is crucial for biological activity.…”

mentioning

confidence: 99%

Synthesis of unsymmetrical biphenyls as potent cytotoxic agents

Guo²,

Gao

et al. 2008

Bioorganic & Medicinal Chemistry Letters

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Twenty-six unsymmetrical biphenyls were synthesized and evaluated for cytotoxic activity against DU145, A547, KB and KB-Vin tumor cell lines. Three compounds 27, 35 and 40 showed very potent activity against the HTCL panel with an IC 50 value range of 0.04-3.23 µM. In addition, fourteen active compounds were all more potent against the drug-resistant KB-Vin cell line than the parental KB cell line. Preliminary SAR analysis indicated that two bulky substituents on the 2,2′-positions of unsymmetrical biphenyl skeleton are necessary and crucial for in vitro anticancer activity, thus providing a good starting point to develop unsymmetrical biphenyls as novel anticancer agents. KeywordsUnsymmetrical biphenyls; Suzuki coupling reaction; Anticancer agents Natural products continue to play a highly significant role today in the discovery and development of new drugs, new leads and new chemical entities. This fact is particularly evident in the areas of cancer and infectious diseases, where over 60% and 75% of drugs, respectively, are of natural origin. 1,2 Dibenzocyclooctandiene lignans have been identified as major bioactive constituents from the traditional Chinese medicinal plant Schizandra chinese and show a wide variety of interesting biological activities, 3, 4 including antiviral, 5 anticancer, 6, 7 hepatoprotective, 8 and anti-inflammatory. 9 Recently, it was also reported that several dibenzocyclooctadiene lignans, such as gomisin A, schisandrins A and B, and schisantherin A, have activity against cancer multidrug resistance mediated by P-glycoprotein (P-gp) and effectively restore the action of anticancer drugs, 10-12 such as vinblastine, daunorubicin, doxorubicin, and VP-16. *Corresponding author. Tel: 86-10-6931690, fax: 86 10 66931690, e-mail address: lanxieshi@yahoo.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Figure 1, and this feature is crucial for biological activity. Structural simplification of the symmetrical wuweizi C to simpler biphenyl analogs led to the anti-hepatotoxic (liver injury) drugs α-DDB (methyl 4,4′-dimethoxy-5,6,5′, 6′-dimethylenedioxy biphenyl-2,2-dicarboxylate) and bicyclol (Figure 1), which are widely used medicinally in China and Asia. In our current study, we decided to focus on unsymmetrical biphenyls, as such compounds have not been previously well explored for cytotoxic activity. NIH Public AccessOur goal was to identify novel biphenyl leads with potent anticancer effects, hopefully with activity against multidrug resistance.Herein, we report the synthesis of twenty-six unsymmetrical biphenyl compounds (18-43) and their...

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Asymmetric Total Synthesis of Dibenzocyclooctadiene Lignan Natural Products

Cited by 30 publications

References 92 publications

Transition metals in organic synthesis: Highlights for the year 2005

Transition metals in organic synthesis: Highlights for the year 2005

Absolute configurations and CD spectra of axially chiral biphenyls prepared in a facile manner by crystallization‐induced configuration transformation

Synthesis of unsymmetrical biphenyls as potent cytotoxic agents

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