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

Abstract

(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...

Passifetilactones A–E, Fatty Acid Lactones from the Fruit and Flowers of Passiflora foetida with Cytotoxic Activity

“…The nine known compounds were identified as patriscabratine, 42 triacetin, 43 2-methoxybenzoic acid, 44 2-hydroxy-5-methoxybenzoic acid, 45 salicylic acid, 46 4hydroxybenzoic acid, 47 capilliplactone, 48 tricin, 49 and 5,7dihydroxy-3′,4′,5′-trimethoxyflavone. 50 T h i s c o n t e n t i s Compound 1 was isolated as a white amorphous solid. Its molecular formula (C 20 H 34 O 2 ) was determined by analysis of the (+)-HRESIMS peak at m/z 329.2451 ([M + Na] + , calcd 329.2451).…”

“…Five previously undescribed fatty acid lactones, which consist of four 2-pyrones with long chains (passifetilactones A–D, 1 – 4 ) and one furanone with a long chain (passifetilactone E, 5 ) are herein described. The nine known compounds were identified as patriscabratine, triacetin, 2-methoxybenzoic acid, 2-hydroxy-5-methoxybenzoic acid, salicylic acid, 4-hydroxybenzoic acid, capilliplactone, tricin, and 5,7-dihydroxy-3′,4′,5′-trimethoxyflavone …”

7-O-Galloyltricetifavan: a promising natural radical scavenger

“…7-O-Galloyltricetifavan (7OGT; figure 1), a natural flavonoid, was first isolated from the leaves of Pithecellobium clypearia [1][2][3]. 7OGT is a flavan derivative that has antiviral properties against respiratory syncytial virus, influenza H1N1 virus, herpes simplex virus type 1 and coxsackie B3 virus as well as anti-inflammatory, anti-Alzheimer, anti-allergic and antioxidant properties [1][2][3][4][5][6][7]. Studies showed that 7OGT has potent xanthine oxidase inhibition with an IC 50 = 25.5 µmol l −1 [3] and inhibits soluble epoxide hydrolase enzymatic activity with IC 50 values 10.0 ± 0.4 µM [5].…”