Synthesis of hydroxyquinones and related compounds: semisquaric acids, (.+-.)-terreic acid, (.+-.)-perezone and (.+-.)-isoperezone

Perezone, a sesquiterpenic benzoquinone with diverse medicinal properties, accumulates in the roots of Acourtia species. In this time-dependent study, the production of perezone was followed in A. cordata culture systems of plants kept in vitro or acclimated and grown in pots. Perezone was characterized by several analytical methods, using the crystallized compound isolated from roots of wild plants as standard. A procedure was developed for its selective quantification, which considers the specific bathochromic shift of the absorbance band in the visible region between the spectra of perezone in its non-ionic and ionic forms, with intensity directly proportional to concentration. In vitro, perezone was recovered from A. cordata roots in average amounts of 5.21 mg g−1 dry weight. Contrastingly, in plants under ex vitro conditions, perezone in roots increased logarithmically, rising from an average of 2.4 mg g−1 dry weight at the 12th week, to 43.6 mg g−1 dry weight at the 31st week, an amount comparable to wild plants. These findings show the feasibility of in vitro and ex vitro culture systems to propagate and conserve the germplasm of perezone-producing Acourtia plants, and a fast and reliable method for the quantification of this valuable compound.

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“…The bands present in the IR spectrum agree perfectly with the vibrational frequencies reported [7,22,24].…”

Section: Characterization Of Perezone Extracted From Wild Plantssupporting

confidence: 85%

Time-dependent perezone production in different culture systems of Acourtia cordata

2012

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“…Sheehan & Lo (1974) reported its total synthesis and an alternative synthesis was published by Enhsen et al (1990). Terreic acid has been identified as a specific inhibitor of Bruton's tyrosine kinase.…”

Section: Further Biological Activitiesmentioning

confidence: 99%

Antimicrobial Butyrolactone I Derivatives from the Ecuadorian Soil Fungus Aspergillus terreus Thorn. var terreus

Cazar

Schmeda-Hirschmann

Astudillo

2005

World J Microbiol Biotechnol

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The fungus Aspergillus terreus Thorn var. terreus isolated from an Ecuador soil sample was cultured in liquid and solid media and yielded three main metabolites identified as terreic acid (1), butyrolactone I (2) and lovastatin (3). The natural products as well as three synthetic butyrolactone I derivatives were assessed for antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi as well as for seed germination and seedling growth. Furthermore, the compounds were assessed as inhibitors towards the enzymes acetylcholinesterase, b-glucosidase, and b-glucuronidase. Terreic acid, butyrolactone I, butyrolactone 4¢,4¢¢-diacetate (2.1), and 3¢-(3-methylbutyl)-butyrolactone II (2.2) were active towards the phytopathogenic bacteria Erwinia carotovora with IC 50 of 5 and 4-18 lg/ml, respectively. Under the same experimental conditions, the IC 50 of streptomycin was 1.9 lg/ml. 3¢-(3-Methylbutyl)-butyrolactone II was moderately active against Pseudomonas syringae and Botrytis cinerea with IC 50 of 21lg/ml and MIC of 15.6 lg/ml, respectively. Butyrolactone I also inhibited germination of the dicot Lactuca sativa with an IC 50 of 5 · 10 )5 M. The IC 50 of reference herbicide acetochlor was 1 · 10 )5 M. The effect of 2.2 and 2.3, known as butyrolactone III on Panicum millaceum germination and growth was stronger than that of 2 and 2.1. Reduction of the double bond in the isoprenyl side chain of butyrolactone I increased the antibacterial effect against E. carotovora as well as acetylation. To our best knowledge, this is the first report on the antibacterial effect of butyrolactone derivatives towards Erwinia carotovora and the phytopathogenic fungus Botrytis cinerea. The butyrolactone I derivative 2.2 presented a moderate inhibitory effect against the enzyme acetylcholinesterase with an IC 50 of 47 lg/ml. Under the same experimental conditions, the reference inhibitor galanthamine had an IC 50 of 3 lg/ml.

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“…Examples of these transformations are shown in Figure 7 and include (±)-septicine [83], perezone [84], lawsone [85], (Z)-multicolanic esters [86] and (E)-basidalin [87]. Also, squaric acid has been found to catalyse reactions involving the N-substituted of pyrroles [88].…”

Section: Z-enolatementioning

confidence: 99%

“…Since the two carbonyl groups in the diketone are the same, the reaction with N-lithiopyrrole yields one product. Other natural product syntheses take advantage of the symmetrical properties of squaryl derivatives and skeletal changes via electrocyclic reactions and include perezone [84] and lawsone [85]. The syntheses of (E)-basidalin [86] and (Z)-multicolanic esters [87] demonstrated a new method to access substituted furanones (Figures 9-12).…”

Section: Figure 8 Synthesis Of (±)-Septicinementioning

confidence: 99%

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Kitson¹

2017

J Diagn Imaging Ther

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Molecular Metaphors is the application of squaryl building blocks towards creative functional group chemistry to produce lead compounds and imaging agents. This strategy is applied to rational drug design and to various imaging agents that would normally contain conventional functional group chemistry. These, include carboxylic acids, α-amino acids, peptide bonds and phosphonates. Moreover, the squaryl metaphor is a precursor to complex organic molecules involving functional group interchange (FGI) and rearrangements. This article discusses the application of these metaphors in the area of neurochemistry, especially NMDA receptors. An important area of drug design is the inhibition of angiotensin II enzyme by the use of losartan. This commercial drug contains a tetrazole moiety that can be modified using the squaryl group to give a semisquarate derivative. These concepts can extend to the semisquarate of ibuprofen. Moreover, a discussion on peptidomimetics regarding the substitution of the peptide bond for squaramide allows for a change in the biological properties due to modification at the peptide bond. Furthermore, the topic on how squaryl metaphors can be exploited primarily by the central 1,3-hydroxyamide sequence to the generation of a novel class of HIV protease inhibitors. Also, squaryl metaphors can be used to develop potential inhibitors of glutathione and novel anti-migraine drugs. The discussion continues on the design of anticancer drugs: in particular, a novel class of metalloproteases, including phosphonates for semisquaramides, leading to squaryl nucleosides. This review concludes with the application of squaryl metaphors in the design of positron emission tomography (PET) and magnetic resonance imaging (MRI) agents towards theranostics. describe the ability of individual functional chemical groups to mimic other moieties [2,3]. KeywordsErlenmeyer rationalised these concepts and categorised isosteres into atoms, ions and molecules based on the valence level of electrons [4]. A further understanding by Friedman led to the term bioisosterism to include all atoms and molecules that fit the broadest definition of isosteres [5]. This approach was independent of whether the drug was an agonist or an antagonist towards biological activity.Moreover, Thornber applied the term bioisosterism to include subunits, groups or molecules that possess physicochemical properties of similar biological effects [6]. Finally, in 1991 Burger widened the definition of bioisosteres to include compounds or groups that possess similar molecular shapes and volumes independent of agonists or antagonists [7]. REVIEW ARTICLE Squaryl KitsonThese bioisosteres would require approximately the same distribution of electrons and give a high probability of generating comparable physical properties such as hydrophobicity [8]. Currently, bioisosterism is one of the most useful tools to the medicinal chemist in rational drug design and in particular regarding the carboxylic acid bioisosteres [9]. The carboxylic acid functional ...

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Synthesis of hydroxyquinones and related compounds: semisquaric acids, (.+-.)-terreic acid, (.+-.)-perezone and (.+-.)-isoperezone

Cited by 71 publications

References 3 publications

Time-dependent perezone production in different culture systems of Acourtia cordata

Time-dependent perezone production in different culture systems of Acourtia cordata

Antimicrobial Butyrolactone I Derivatives from the Ecuadorian Soil Fungus Aspergillus terreus Thorn. var terreus

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

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