3555-86-0Relevant articles and documents
Synthesis of 3-geranyl- and 3-prenyl-2,4,6-trihydroxybenzophenone
Mzozoyana, Vuyisa,van Heerden, Fanie R.
, p. 599 - 603 (2017)
Biologically active phenyl[3-(3,7-dimethyl-2,6-octadienyl)-2,4,6-trihydroxyphenyl]methanone (2) and phenyl[2,4,6-trihydroxy-3-(3-methyl-2-butenyl)phenyl]methanone (3) were synthesized by an efficient and convenient synthetic sequence. The reaction steps of this synthesis included methylation, Friedel-Crafts acylation, demethylation and geranylation steps.
Biomimetic total synthesis of (±)-garcibracteatone
Pepper, Henry P.,Lam, Hiu C.,Bloch, Witold M.,George, Jonathan H.
, p. 5162 - 5164,3 (2012)
The polycyclic polyprenylated acylphloroglucinol natural product garcibracteatone has been synthesized in four steps from phloroglucinol, using a strategy based on biosynthetic speculation. The key biomimetic transformation is a cascade of 7-endo-trig and 5-exo-trig radical cyclizations followed by a terminating aromatic substitution reaction.
Synthesis of fluorine-containing prenylated benzophenones
Mzozoyana, Vuyisa,van Heerden, Fanie R.
, p. 2226 - 2235 (2020/07/09)
In this study, an effective route to synthesize fluorine-containing prenylated benzophenones was developed. Friedel–Crafts acylation and electrophilic aromatic substitution reactions were the key reactions of this synthesis to achieve these fluorinated prenylated benzophenones. The use of DBU in the prenylation step achieved only the C-prenylated benzophenones, whereas K2CO3 produced the C- and O-prenylated benzophenones.
Expedient Synthesis of Lupulones and Their Derivatization to 2,8-7H-Dihydrochromen-7-ones
Blondeel, Eline,D'hooghe, Matthias,Decuyper, Lena,Depetter, Yves,Kaur, Gurkirat,Van Hecke, Kristof,Versyck, Charlotte
, p. 442 - 444 (2020/10/02)
A convenient and improved method for the synthesis of beta acids or lupulones, which are known to possess e. g. anti-cancer, anti-inflammatory, anti-oxidative and antimicrobial activity, has been developed successfully. Further derivatization of these complex structures to the corresponding dihydrochromen-7-ones, including the natural product machuone, was realized to simplify their analysis and to confirm their molecular structure. In addition to practical and safe laboratory procedures, the advantages associated with this new approach involve the use of water as a solvent and the direct crystallization of lupunones from acetonitrile, rendering our strategy more efficient and benign as compared to available methods.
The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa
Zhao, Weining,Cross, Ashley R.,Crowe-McAuliffe, Caillan,Weigert-Munoz, Angela,Csatary, Erika E.,Solinski, Amy E.,Krysiak, Joanna,Goldberg, Joanna B.,Wilson, Daniel N.,Medina, Eva,Wuest, William M.,Sieber, Stephan A.
, p. 8581 - 8584 (2019/05/28)
Natural products represent a rich source of antibiotics that address versatile cellular targets. The deconvolution of their targets via chemical proteomics is often challenged by the introduction of large photocrosslinkers. Here we applied elegaphenone, a largely uncharacterized natural product antibiotic bearing a native benzophenone core scaffold, for affinity-based protein profiling (AfBPP) in Gram-positive and Gram-negative bacteria. This study utilizes the alkynylated natural product scaffold as a probe to uncover intriguing biological interactions with the transcriptional regulator AlgP. Furthermore, proteome profiling of a Pseudomonas aeruginosa AlgP transposon mutant provided unique insights into the mode of action. Elegaphenone enhanced the elimination of intracellular P. aeruginosa in macrophages exposed to sub-inhibitory concentrations of the fluoroquinolone antibiotic norfloxacin.
Total synthesis of acylphloroglucinols and their antibacterial activities against clinical isolates of multi-drug resistant (MDR) and methicillin-resistant strains of Staphylococcus aureus
Rahman, M. Mukhlesur,Shiu, Winnie K.P.,Gibbons, Simon,Malkinson, John P.
supporting information, p. 255 - 262 (2018/06/20)
Bioassay-directed drug discovery efforts focusing on various species of the genus Hypericum led to the discovery of a number of new acylphloroglucinols including (S,E)-1-(2-((3,7-dimethylocta-2,6-dien-1-yl)oxy)-4,6-dihydroxyphenyl)-2-methylbutan-1-one (6, olympicin A) from H. olympicum, with MICs ranging from 0.5 to 1 mg/L against a series of clinical isolates of multi-drug-resistant (MDR) and methicillin-resistant Staphylococcus aureus (MRSA) strains. The promising activity and interesting chemistry of olympicin A prompted us to carry out the total synthesis of 6 and a series of analogues in order to assess their structure-activity profile as a new group of antibacterial agents. Following the synthesis of 6 and structurally-related acylphloroglucinols 7–15 and 18–24, their antibacterial activities against a panel of S. aureus strains were evaluated. The presence of an alkyloxy group consisting of 8–10 carbon atoms ortho to a five-carbon acyl substituent on the phloroglucinol core are important structural features for promising anti-staphylococcal activity.
Friedel-Crafts Alkylation of Acylphloroglucinols Catalyzed by a Fungal Indole Prenyltransferase
Zhou, Kang,Ludwig, Lena,Li, Shu-Ming
, p. 929 - 933 (2015/05/05)
Naturally occurring prenylated acylphloroglucinol derivatives are plant metabolites with diverse biological and pharmacological activities. Prenylation of acylphloroglucinols plays an important role in the formation of these intriguing natural products and is catalyzed in plants by membrane-bound enzymes. In this study, we demonstrate the prenylation of such compounds by a soluble fungal prenyltransferase AnaPT involved in the biosynthesis of prenylated indole alkaloids. The observed activities of AnaPT toward these substrates are much higher than that of a microsomal fraction containing an overproduced prenyltransferase from the plant hop.
Synthesis and biological evaluation of novel myrtucommulones and structural analogues that target mPGES-1 and 5-lipoxygenase
Wiechmann, Katja,Müller, Hans,Huch, Volker,Hartmann, David,Werz, Oliver,Jauch, Johann
, p. 133 - 149 (2015/07/07)
The natural acylphloroglucinol myrtucommulone A (1) inhibits microsomal prostaglandin E2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), and induces apoptosis of cancer cells. Starting from 1 as lead, 28 analogues were synthesized following a straightforward modular strategy with high yielding convergent steps. Major structural variations concerned (I) replacement of the syncarpic acid moieties by dimedone or indandione, (II) cyclization of the syncarpic acid with the acylphloroglucinol core, and (III) substitution of the methine bridges and the acyl residue with isopropyl, isobutyl, n-pentyl or phenyl groups, each. The potency for mPGES-1 inhibition was improved by 12.5-fold for 43 (2-(1-(3-hexanoyl-2,4,6-trihydroxy-5-(1-(3-hydroxy-1-oxo-1H-inden-2-yl)-2-methylpropyl)phenyl)-2-methylpropyl)-3-hydroxy-1H-inden-1-one) with IC50 Combining double low line 0.08 μM, and 5-LO inhibition was improved 33-fold by 47 (2-((3-hexanoyl-2,4,6-trihydroxy-5-((3-hydroxy-1-oxo-1H-inden-2-yl) (phenyl)methyl)phenyl) (phenyl)methyl)-3-hydroxy-1H-inden-1-one) with IC50 Combining double low line 0.46 μM. SAR studies revealed divergent structural determinants for induction of cell death and mPGES-1/5-LO inhibition, revealing 43 and 47 as non-cytotoxic mPGES-1 and 5-LO inhibitors that warrant further preclinical assessment as anti-inflammatory drugs.
Rapid preparation of (methyl)malonyl coenzyme A and enzymatic formation of unusual polyketides by type III polyketide synthase from Aquilaria sinensis
Gao, Bo-Wen,Wang, Xiao-Hui,Liu, Xiao,Shi, She-Po,Tu, Peng-Fei
supporting information, p. 1279 - 1283 (2015/03/14)
(Methyl)malonyl coenzyme A was rapidly and effectively synthesized by a two-step procedure involving preparation of N-hydroxysuccinimidyl (methyl)malonate from (methyl)Meldrum's acid, and followed by transesterification with coenzyme A. The synthesized (methyl)malonyl coenzyme A could be well accepted and assembled to 4-hydroxy phenylpropionyl coenzyme A by type III polyketide synthase from Aquilaria sinensis to produce dihydrochalcone and 4-hydroxy-3,5-dimethyl-6-(4-hydroxyphenethyl)-2H-pyrone as well as 4-hydroxy-3,5-dimethyl-6-(5-(4-hydroxyphenyl)-3-oxopentan-2-yl)-2H-pyrone.
Facile formation of methylenebis(chalcone)s through unprecedented methylenation reaction. Application to antiparasitic and natural product synthesis
Thevenin, Marion,Mouray, Elisabeth,Grellier, Philippe,Dubois, Joelle
, p. 2986 - 2992 (2014/05/20)
The formation of methylenebis(chalcone)s has been discovered during deprotection with methoxymethyl groups from trihydroxychalcones. Studies on this methylenation reaction led to a mechanism hypothesis that was extended to other chalcones and to dihydrochalcone, acetophenone, benzophenone and flavone derivatives. This new method was applied to the rapid synthesis of natural product piperanduncin C. These original methylenebis compounds were also evaluated for their antiparasitic activity. Copyright
