6,6′-Dimethoxygossypolone

Zelaya, Carlos A.; Stevens, Edwin D.; Dowd, Michael K.

doi:10.1107/s0108270110036541

Cited by 3 publications

(2 citation statements)

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“…2010). Structurally, conversion of the inner benzyl rings to quinone rings allows for modest flexibility of the napthyl ring structure (Zelaya et al. 2010), which may allow for stronger interactions with enzyme‐binding sites.…”

Section: Discussionmentioning

confidence: 99%

“…Growth inhibitory activities of benzoic acid analogues against A. flavus have been linked to disruption of mitogen-activated protein kinase signal transduction systems (Kim et al 2010). Structurally, conversion of the inner benzyl rings to quinone rings allows for modest flexibility of the napthyl ring structure (Zelaya et al 2010), which may allow for stronger interactions with enzyme-binding sites. That apogossypolone was more effective than either gossypol or gossypolone also suggests that the aldehyde moieties are not absolutely necessary for activity.…”

Section: Discussionmentioning

confidence: 99%

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Inhibitory effects of gossypol-related compounds on growth of Aspergillus flavus

Mellon

Zelaya

Dowd

2011

Letters in Applied Microbiology

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Aims: The objective of this study was to test a series of gossypol‐related compounds for growth inhibition against Aspergillus flavus. Methods and Results: A series of chiral and achiral gossypol derivatives, some natural products of the cotton plant and others prepared by synthesis from gossypol, were incorporated into agar plates to follow the rate of A. flavus isolate AF13 colony growth. All tested compounds exhibited some growth inhibition against this organism. The synthetic compounds, gossypolone and apogossypolone, exhibited greater activity than either racemic or chiral gossypol. Methylated derivatives (i.e. 6‐methoxy and 6,6′‐dimethoxy derivatives) generally exhibited less activity than the nonmethylated parent compounds. The (−)‐optical form of gossypol was found to be slightly more active than the (+)‐optical form, and this trend was observed regardless of the presence of methoxy groups at the 6‐position. Growth inhibition of gossypolone and apogossypolone was concentration dependent. For gossypolone, the 50% effective dose was 90 μg ml−1 of medium (165 μmol l−1). For apogossypolone, the most active compound in the study, the 50% effective dose was 19 μg ml−1 (38·7 μmol l−1). The presence of gossypol‐related terpenoids appeared to stimulate production of A. flavus sclerotia, although replicate variability was so large that it was not possible to determine a significant correlation between the mass of sclerotia formed and compound growth inhibition. Conclusions: The quinone derivatives of gossypol, gossypolone and apogossypolone demonstrated significant fungal growth inhibitory activity against A. flavus. Significance and Impact of the Study: These gossypol derivatives may provide a new class of fungicide for use against the mycotoxigenic fungus A. flavus.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of gossypol-related compounds on growth of Aspergillus flavus

Mellon

Zelaya

Dowd

2011

Letters in Applied Microbiology

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Enantioselective Total Synthesis and Studies into the Configurational Stability of Bismurrayaquinone A

et al. 2011

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The carbazole alkaloids represent a large and structurally rich family of natural products that are produced by a variety of terrestrial plants. [1] In particular, plants within the Rutaceae family are notable producers of these compounds-with the genus Murraya providing the greatest number of unique structures. Commonly found in the outer Himalayas and on the Indian peninsula, the leaves of M. koenigii (L.) Spreng are, inter alia, extensively utilized as a spice flavoring by the peoples of these areas giving it the name "curry-leaf tree". Extracts of the plant are also used in local medicine due to their antimicrobial activity. [2] Within this large family of alkaloids, we were particularly interested in the axially chiral dimeric carbazoles, [3] and most specifically bismurrayaquinone A (1, Figure 1). This unique dimeric carbazolequinone was isolated from the roots of M. koenigii (L.) Spreng by Furukawa and coworkers in 1993 [4] and has been the subject of non-stereoselective total syntheses by the groups of both Bringmann and Murphy. [5] Somewhat surprisingly, there has never been an enantioselective synthesis of 1. Bringmann and coworkers did, however, prepare racemic 1 and separated the two enantiomers using preparative HPLC, [5a] and in 2001 reported an approach towards a stereoselective synthesis. [6] Because no enantioselective synthesis of bismurrayaquinone A (1) had been reported, and because there is very little literature data on axially chiral biquinones, [7] we were compelled to explore strategies for the enantioselective synthesis of these molecules. Recently, we reported the development of a new method for synthesizing enantiomerically pure axially chiral biphenols by a method we termed "traceless stereochemical exchange". [8] This method allows ready access to biphenols of the type represented by structure 2 (Figure 1), and herein we report the use of this method to conduct the first enantioselective synthesis of bismurrayaquinone A (1). These studies have also revealed a fascinating phenomenon related to the configurational stability of chiral biquinones.Our synthesis of bismurrayaquinone A (1) commenced from commercially available 4-methoxyphenol (3), which was converted into enone 4 following oxidation to the corresponding dimethylketal quinone [9] and subsequent enantioselective conjugate addition of dimethylzinc (Scheme 1). [10] ** This work was supported by the National Institutes of Health (1R01GM085322), Northwestern University (NU) and Amgen. The efficiency of the Feringa conjugate addition in terms of yield dropped from 52% on a 5 gram scale to 45% yield when conducted on 10 grams, but the enantioselectivity was maintained at 99% ee. Gram-scale oxidative dimerization of 4 was conducted under our reported conditions [8] to provide dione 5 in 63% yield (99% ee). [11] Conversion of dione 5 to bromophenol 6 proceeded smoothly after aromatization to 2 (not shown) and regioselective bromination. Our plan at this juncture was to utilize methods for palladiumcatalyzed carbazolequinone synthes...

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Enantioselective Total Synthesis and Studies into the Configurational Stability of Bismurrayaquinone A

et al. 2011

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Lost in rotation: The concise strategy of the first enantioselective total synthesis of bismurrayaquinone A utilized traceless stereochemical exchange to form an enantioenriched biphenyl core that was elaborated in a bidirectional manner to the natural product. Observed racemization on an unsuccessful initial route prompted studies into the configurational stability of bismurrayaquinone A and related biquinones.

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6,6′-Dimethoxygossypolone

Cited by 3 publications

References 20 publications

Inhibitory effects of gossypol-related compounds on growth of Aspergillus flavus

Inhibitory effects of gossypol-related compounds on growth of Aspergillus flavus

Enantioselective Total Synthesis and Studies into the Configurational Stability of Bismurrayaquinone A

Enantioselective Total Synthesis and Studies into the Configurational Stability of Bismurrayaquinone A

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