Synthesis of 5- and/or 7-Hydroxyflavones using A Modified Phase Transfer-Catalysed Baker-Venkataraman Transformation

Saxena, Shabnam; Makrandi, J. K.; Grover, S. K.

doi:10.1055/s-1985-31319

Cited by 35 publications

(13 citation statements)

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“…Elemental analyses of all compounds agreed with those calculated. 5,7-Dihydroxyflavone was prepared as before [35]. N-Substituted 7-O-Aminoacyl-5-hydroxy-2-phenylchromen-4-ones 2-20.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of amino-acid derivatives of chrysin

et al. 2008

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Various conjugates of amino acids with chrysin in which the amino acid was bonded through the C-or N-terminus to the flavone were prepared using peptide chemistry methods (symmetric anhydrides and activated esters).Flavonoids are the most widely distributed compounds of natural origin. They can be found in practically all plant species. At present, flavonoids comprise about 6500 natural compounds [1]. The study of flavonoids is becoming increasingly interesting because of the important role that they play in the metabolism of plants and animals and their high and diversified biological activity [2]. Chrysin (5,7-dihydroxyflavone) is one of the most common flavonoids, has been isolated from various plant families [3,4], and possesses, like its derivatives, a broad spectrum of biological activity. Thus, chrysin exhibits anticancer [5,6], antioxidant [7, 8], anti-inflammatory [9, 10], vasodilating [11, 12], immunomodulating [13, 14], antibacterial [15, 16], antifungal [16], antiprotozal [17], neuroprotective [18], hypotensive [19], and anti-allergy [20] activity. Chrysin derivatives possess hypoglycemic [21], anticancer [22-25], anti-inflammatory [26, 27], and antibacterial [15] action.Considering the importance to the metabolism of all animals of amino acids and their derivatives, our goal was to synthesize chrysin derivatives with pharmacophores containing amino acids.The amino-acid derivatives of chrysin were synthesized via two modification pathways. The first was based on formation of the ester of N-protected amino acid and phenolic compounds. The most suitable and convenient method for synthesizing 7-O-amino-acid chromone derivatives is the reaction of 7-hydroxychromones and symmetric anhydrides of N-substituted amino acids because the reaction proceeds under mild conditions and is not complicated by side reactions [28]. It has been used successfully to synthesize similar types of compounds [29,30].The hydroxyls of 5,7-dihydroxychromones have different reactivities because of the different influence of electrondonors, steric factors, and intramolecular H-bonds. Therefore, the 7-hydroxyl of the chromone system is acylated exclusively under mild conditions [31,32].Symmetric anhydrides of N-protected amino acids were prepared by reaction of dicyclohexylcarbodiimide (DCC) with two equivalents of the corresponding N-protected amino acid in anhydrous dioxane at 0°C. The amines of the amino acids were blocked with t-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), and p-toluenesulfonic acid (Tos). Chrysin was acylated by the resulting amino-acid anhydrides at 0°C in anhydrous dioxane in the presence of catalytic amounts of 4-dimethylaminopyridine (DMAP) to produce N-protected 7-O-aminoacyl-5-hydroxy-2-phenylchromen-4-ones 2-20. The products contained glycine (2, 8), L-alanine (3, 9), L-valine (4, 10), L-leucine (5, 11), L-isoleucine (6, 12), L-methionine (13), L-phenylalanine (7, 14), β-alanine (15, 17, 19), and 6-aminohexanoic acid (16, 18, 20).The selective acylation of the chromone 7-hydroxyl was confirmed by PMR ...

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“…Elemental analyses of all compounds agreed with those calculated. 5,7-Dihydroxyflavone was prepared as before [35]. N-Substituted 7-O-Aminoacyl-5-hydroxy-2-phenylchromen-4-ones 2-20.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of amino-acid derivatives of chrysin

et al. 2008

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“…The mixture was redissolved in methanol (60 mL), CH 3 ONa (2.32 g) was added, the solution was then stirred for 30 min at r.t. until 2 M HCl (aq, 18 mL) was added to adjust the pH to 6-7. (9). To a solution of compound 6 (600 mg, 1.14 mmol) in 5 mL of dry acetone was added dimethyl sulfate (238 mL, 2.51 mmol) and anhydrous K 2 CO 3 (472 mg, 3.42 mmol), and the mixture was stirred for 5 h at 56 C. The solution was concentrated, redissolved in EtOAc washed with water, dried with Na 2 SO 4 , ltered, and then concentrated to give a brown oil.…”

Section: General Experimental Proceduresmentioning

confidence: 99%

A concise synthesis of (±)-7-O-galloyltricetiflavan

et al. 2018

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(AE)-7-O-galloyltricetiflavan (1a) was synthesized successfully in five steps from the commercially available trihydroxyacetophenone (2) and trimethoxybenzoyl chloride (3). The flavone 4a was prepared in a one-pot reaction and it gave hex-O-methylflavan 6 followed by acylation and reduction. However, the demethylation of flavan 6, 5-O-acetylflavan 10 and 5-O-phenylacetylflavan 11 by BBr 3 gave all the hydrolyzed fragments 7 and 8 as the major products. By contrast, in the same condition, hept-Omethylflavan 9 could provide the desired product (AE)-7-O-galloyltricetiflavan (1a) in 91% yield. The additional 5-O-B-Br 2 complex may stabilize the ester bond during the demethylation process.(À)-7-O-Galloyltricetiavan (1, Fig. 1) was isolated from a methanolic extract of the leaves of Pithecellobium clypearia by Ooi V. and coworkers in 2006.1 It is a catechin-like compound without an OH substituent at C-3, and it shows good antiviral activities against respiratory syncytial virus (RSV), inuenza A (H1N1) virus, coxsackie B3 (Cox B3) virus and herpes simplex virus type 1 (HSV-1) as well as anti-inammatory and anti-allergic activities.2-5 To date, the preparation of (À)-7-O-galloyltricetiavan (1) still requires extraction and purication of plant material, and only a few synthetic examples of this type of avan have been reported.6,7 Herein we report the rst total synthesis of (AE)-7-Ogalloyltricetiavan (1a) in ve steps as well as an interesting discovery during the demethylation process.The synthesis of (AE)-7-O-galloyltricetiavan (1a) was started from the preparation of the avone derivative 4a as shown in Scheme 1. Buckle's group reported an efficient one-pot synthesis of avones by the treatment of 2-hydroxyacetophenones with the corresponding aroyl chloride in wet K 2 CO 3 /acetone (1% w/w water), 8 but the reaction proceeded very slowly because the trihydroxyacetophenone (2) was insoluble in acetone. With water-toluene as the solvent, in the presence of K 2 CO 3 and tetrabutylammonium hydrogen sulfate, 9 the reaction could provide avone 4a in 30% yield and 3-acylated product 4b in 50% yield in one-pot in about two hours. Many efforts to improve the yield of 4a failed, but 4b could be converted into 4a by hydrolysis in 50% yield.10 Aerwards, acylation of 4a with trimethoxybenzoyl chloride (3) and K 2 CO 3 gave 7-Ogalloylavone 5 in 91% yield, which was then reduced to the avan 6 by hydrogenation with palladium on carbon as the catalyst for 3 days in 62% yield. 11When avan 6 was treated with BBr 3 in dichloromethane at À40 C or À78 C, 12 the desired product 1a was generated in only 3% yield (based on HPLC-MS analysis), accompanied with 4-O-methyl gallic acid (7) and avan 8 as the major products, indicating the ester bond of hex-O-methylavan 6 is highly unstable under acidic conditions (Scheme 1).Then, 5-O-methylavan 9, 5-O-acetylavan 10 and 5-O-phenylacetylavan 11 were prepared as substrates to explore if they provided different results (Scheme 2). Similarly, 5-O-acetylavan 10 and 5-O-phenylacetylava...

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“…5 The condensation of polylithiated enolates, generated from hydroxylated acetophenones and an excess of lithium diisopropylamide, with benzoyl chlorides or methyl benzoates gives the 1,3-diketone intermediates, which are cyclodehydrated with sulfuric acid in HOAc to afford hydroxyflavones. 6 1,3-Diketones are also prepared by the reaction of 2'-hydroxyacetophenones and benzoyl chlorides with potassium carbonate using phase transfer catalyst 7 or the rearrangement of 2-acetylphenyl benzoates with bases such as KOH in pyridine 8 and K2CO3 in acetone, 9 but the former requires an excess of benzoyl chlorides and the latter proceeds in moderate yields or requires prolonged reaction time. The oxidative cyclization of 2'-hydroxychalcones, derived from the condensation of 2'-hydroxyacetophenones with benzaldehydes or the acylation of methoxy substituted phenols with cinnamoyl chloride, with PhI(OAc)2/KOH in CH3OH, 10 I2-triethylene glycol, 11 Wittig olefination, in which phosphoranes, derived from o-hydroxyphenacyl chloride or o-benzoyloxyphenacyl bromide and triphenylphosphine, are condensed with benzoyl chlorides to afford hydroxyflavones after saponification in multiple steps from 2'-hydroxyacetophenones.…”

Section: Introductionmentioning

confidence: 99%