Short communicationSynthesis of Abyssinone II and related compounds as potential chemopreventive agents
Introduction
Flavonoids constitute an important class of naturally occurring compounds exhibiting a wide spectrum of biological activities, which include anti-carcinogenic, anti-viral, anti-inflammatory and anti-fungal properties [1]. The remarkable biological effect of hydroxy flavonoids is mainly attributed to the presence of phenolic groups, which have high affinity for proteins and therefore act as inhibitors of microbial enzymes [2] as well as through their effect on uncoupling oxidative phosphorylation [3] and inhibition of NADH dehydrogenase of mitochondrial inner membranes [4].
In addition, substitution on the flavonoid ring system with prenyl groups is thought to increase their lipophilicity and consequently enhance their lipophilicity through interaction with cellular membranes [5].
It is generally agreed that one phenolic group and certain degree of lipophilicity are required for the activity of the flavonoid compounds [6]. In spite of the diversity of biological activity exhibited by the prenylated flavonoids, there is little information as to the structure–activity relationship. However, it appears that the position of prenylation rather than the number of prenyl groups, determines the biological activity of the compounds [7].
Notably, there is substantial evidence that a high intake of flavonoids lowers cancer risk [8], [9]. Last decade has witnessed an explosion of research publication on the use of flavonoids as cancer chemopreventive agents [8], [9]. A large number of flavonoids have been used for the chemopreventive studies in vivo, in vitro and in human clinical trials [8], [9]. Flavonoids have shown promise to inhibit carcinogenesis by acting via a series of mechanisms by affecting the molecular events at the initiation and progression stages [8], [9]. Hydroxy flavonoids with prenyl group have been shown to be aromatase inhibitors. The enzyme aromatase catalyses the final and rate-limiting step in estrogen biosynthesis. The overall hypothesis is that these compounds will be safe and effective inhibitors of estrogen-dependent tumor formation.
Section snippets
Results and discussion
In continuation of our ongoing research in the area of cancer chemoprevention, we have synthesized Abyssinone II, 7-hydroxy-2-[4-hydroxy-3-(methyl-but-2-enyl) phenyl] chroman-4-one (15) and its derivatives. Abyssinone (II) has been isolated from the Chinese medical plant Broussonetia papyfera. It has been found to be one of the most active naturally occurring aromatase inhibitors and has exhibited higher potency than aminoglutethinide [10]. The National Cancer Institute selected Abyssinone (II)
Experimental
All moisture-sensitive reactions were carried out under an argon atmosphere in flame-dried glassware. Solvents and reagents were purchased from Aldrich. Tetrahydrofuran (THF) was distilled from sodium/benzophenone. Dichloromethane (DCM) and triethylamine were distilled from calcium hydride. Thin layer chromatography (TLC) was carried out on Aldrich silica gel glass plates with UV indicator. Flash column chromatography was performed on Merck silica gel 60 (mesh 230–400). 1H- and 13C-NMR spectra
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Antimicrobial, antimalarial and anticholinesterase substances from the marine-derived fungus Aspergillus terreus BCC51799
2020, TetrahedronCitation Excerpt :Compounds 4, 17, 20, 29, and 30 were isolated as natural products for the first time. Comparison with the 1H and 13C NMR spectral data described in the literature, the known compounds were identified as butyrolactones I (6) [11], II (2) [11], IV (9) [12], V (8) [13], VI (5) [14], aspernolides A – C (7, 3, and 4) [15], 3-hydroxy-5-[4-hydroxy3-(3-(3-methyl-2-buten-1-yl)phenyl]methyl]-4-(4-hydroxyphenyl)-2-(5H)-furanone (10) [16], a mixture of aspulvinone E and isoaspulvinone E (11) [17], aspulvinones O (12) [9] and D (15) [18], luteoride E (16) [19], astechrome (18) [10], asterriquinone CT5 (22) [20], methyl 3,4,5-trimethoxy-2-(2-(nicotinamide)benzamido)benzoate (23) [21], (+)-alantrypinone (24) [22], lavastatin (25) [23], territrem B (26) [24], cis-4,6-dihydroxymellein (27) [25], cis-4-hydroxykigelin (28) [26], 4-hydroxy-3-(3-methylbut-2-enyl)benzaldehyde (29) [27], methyl 2-(4-hydroxy-3-(3-methylbut-2-en-1-yl)phenyl)acetate [28], and indole-3-methyl acetate (31). The fact that compound 18 could not be clearly detected by 1H NMR spectrum [10], it was thus confirmed by HRESIMS spectrum and hydrolyzed with 2 N NaOH to give compound 17.
New isoflavans from the root bark of Erythrina livingstoniana
2016, Phytochemistry LettersCitation Excerpt :Thus, compound 2 was characterized as 7,2⿲-dihydroxy-[6⿲⿲,6⿲⿲-dimethyl pyrano(2⿲⿲,3⿲⿲:4⿲,5⿲)] isoflavan and is being reported here for the first time, and is trivially named erylivingstone K. Other known compounds identified along with the new compounds include 2⿲-methoxyphaseollinisoflavan (3) (Tanaka et al., 1998), 7,4⿲-dihydroxy-2⿲,5⿲-dimethoxy isoflavan (4) (Tanaka et al., 2005), 7,4⿲-dihydroxy-2⿲-methoxy-3⿲-(3-methylbut-2-enyl) isoflavan (5) (Preston, 1975), calopocarpin (6) (Yenesew et al., 1998), isoneorautenol (7) (Ingham, 1985), eryvarin L (8) (Tanaka et al., 2003), licoagrochalcone A (9) (Yenesew et al., 2003), abyssinone II (10) (Moriarty et al., 2006). The complete 13C NMR data of compound 5 is reported here for the first time (see experimental part).
Recent advances of chroman-4-one derivatives: Synthetic approaches and bioactivities
2015, European Journal of Medicinal ChemistryCitation Excerpt :Feng et al. designed and synthesized a series of 2-alkylchromanone antibacterials based on the structures of abyssinone II and olympicin A (Fig. 55) [69]. Abyssinone II, 7-hydroxy-2-[4-hydroxy-3-(methyl-but-2-enyl)phenyl]chroman-4-one has been isolated from the Chinese medical plant Broussonetia papyfera [70,71]. Olympicin A is new antibacterial acylphloroglucinol which isolated from the aerial parts of the plant Hypericum olympicum L. cf. uniflorum [72,73].
Synthetic racemates of abyssinone i and II induces apoptosis through mitochondrial pathway in human cervix carcinoma cells
2014, Bioorganic ChemistryCitation Excerpt :Thus abyssinones gained importance and hence scientists started synthesizing these molecules to study their biological activities. Moriaty et al. synthesized abyssinone II and reported their aromatase inhibitory activity [14]. However, the molecular mechanisms involved in initiation of cell death, the targets and the anticancer action of abyssinones are not completely understood.
First total synthesis of four natural prenylated flavonoids
2012, Chinese Chemical LettersBiosynthesis of fomannoxin in the root rotting pathogen Heterobasidion occidentale
2012, PhytochemistryCitation Excerpt :Compound 1 has never been found in any natural source but has been synthesized (Kyogoku et al., 1975) and has been used as an intermediate for the total synthesis of natural products flavanoids (Khan and Krishnamurti, 1983; Moriarty et al., 2006. The acquired NMR data for compound 1 was in good agreement with data previously reported for 1 (Moriarty et al., 2006). Of the fomannoxin related compounds 1–4 only compounds 1 and 2 were isolated in amounts sufficient for studies of the labeling pattern.