Novel Synthesis of Flavonoids of Scutellaria baicalensis GEORGI

School of Pharmacy, National Defense Medical Center, Taiwan.
CHEMICAL & PHARMACEUTICAL BULLETIN (Impact Factor: 1.16). 04/2003; 51(3):339-40. DOI: 10.1248/cpb.51.339
Source: PubMed


A concise and efficient total synthesis of the flavonoids baicalein, oroxylin A and wogonin was described. Intramolecular oxidative cyclization followed by demethylation of chalcone 1, readily prepared from trimethoxyphenol, afforded, depending upon the controlled conditions, baicalein or oroxylin A in excellent yields. Demethylation of 1 yielded 3, which, by oxidation with I(2)/dimethyl sulfoxide (DMSO), was readily converted to oroxylin A and wogonin after column chromatography.

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    • "A phytochemical investigation of the ethyl acetate extract of C. scoparia aerial parts led to the isolation of two new (1-2) and eight known (3–10) flavonoids isolated for the first time from this plant (Figure 1). The structures of the new compounds 3′,4′-dihydroxy-(3′′,4′′-dihydro-3′′-hydroxy-4′′-acetoxy)-2′′,2′′-dimethylpyrano-(5′′,6′′:7,8)-flavone-3-O-β-D-gulcopyranoside (1) and 3,3′,4′-trihydroxy-(3′′,4′′-dihydro-3′′,4′′-dihydroxy)-2′′,2′′-dimethylpyrano-(5′′,6′′:7,8)-flavone (2) were elucidated by means of spectroscopic tools and the known compounds were identified as cynaroside (3) [18], Apigetrin (4) [19], centaureidin (5) [20, 21], oroxylin A (6) [22, 23], 5,7-dihydroxy-3′,4′,5′-trimethoxyflavone (7) [24, 25], atalantoflavone (8) [26], 5-hydroxy-3′,4′,8-trimethoxy-2′′,2′′-dimethylpyrano (5′′,6′′:6,7)-flavone (9) [27, 28], and 3′,4′,5,8-tetramethoxy-2′′,2′′-dimethylpyrano (5′′,6′′:6,7)-flavone (10) [27, 28]. "
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    ABSTRACT: Phytochemical studies on the ethanolic extract of the aerial parts of Centaurea scoparia led to the isolation of two new flavonoids, 3',4'-dihydroxy-(3'',4''-dihydro-3''-hydroxy-4''-acetoxy)-2'',2''-dimethylpyrano-(5'',6'':7,8)-flavone-3-O- β -D-glucopyranoside (1) and 3,3',4'-trihydroxy-(3'',4''-dihydro-3'',4''-dihydroxy)-2'',2''-dimethylpyrano-(5'',6'':7,8)-flavone (2), along with eight known flavonoids isolated for the first time from this plant, cynaroside (3), Apigetrin (4), centaureidin (5), oroxylin A (6), 5,7-dihydroxy-3',4',5'-trimethoxyflavone (7), atalantoflavone (8), 5-hydroxy-3',4',8-trimethoxy-2'',2''-dimethylpyrano (5'',6'':6,7)-flavone (9), and 3',4',5,8-tetramethoxy-2'',2''-dimethylpyrano (5'',6'':6,7)-flavone (10). The structures of the isolated compounds were elucidated by means of spectroscopic tools including 1D and 2D NMR, UV, IR, and mass spectroscopy. Cytotoxic activities of the isolated compounds were evaluated against human cervical carcinoma HeLa, human hepatocellular carcinoma HepG2, and human breast carcinoma MCF-7. Compound 2 was the most potent cytotoxic agent against HeLa cells with an IC50 0.079 μ M.
    Full-text · Article · Jun 2014 · The Scientific World Journal
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    • "The synthesis of oroxylin A derivatives has been reported elsewhere (Huang et al., 2003; Park et al., 2005). In particular, the oroxylin A derivative compound 7-7 (3) was synthesized from commercial starting materials in 3 steps. "
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    ABSTRACT: Oroxylin A, a major flavonoid in Scutellaria baicalensis, has been shown to alleviate attention-deficit/hyperactivity disorder (ADHD)-like behaviors in the Spontaneously Hypertensive rat (SHR) model of ADHD. As part of our continuing effort to discover effective ADHD drug candidates, we synthesized a number of oroxylin A derivatives and characterized their biological activities. Among all oroxylin A analogues, compound 7-7 (5,7-dihydroxy-6-methoxy-4'-phenoxyflavone) showed the most remarkable inhibition of dopamine reuptake alike methylphenidate, a dopamine transporter (DAT) blocker and typical drug for ADHD, and oroxylin A. It did not influence norepinephrine reuptake unlike atomoxetine, a selective norepinephrine inhibitor. Moreover, compound 7-7 reduced hyperactivity, sustained inattention and impulsivity in the SHR as measured by the open field, Y-maze and electro-foot shock aversive water drinking tests, respectively. Most drugs that enhance brain dopamine levels (e.g. DAT blockers like cocaine and methylphenidate) produce behavioral effects like those of stimulants causing them to be abused. However, the repeated treatment of compound 7-7 failed to elicit locomotor sensitization in rats, and neither produced conditioned place preference response nor maintained self-administration behavior. Altogether, the present study suggests the promising therapeutic value of compound 7-7as an ADHD drug. Furthermore, compound 7-7 may be considered as an alternative therapy to psychostimulant ADHD treatments (e.g. amphetamine and methylphenidate) for which use has been deemed controversial due to their abuse liability.
    Full-text · Article · May 2013 · European journal of pharmacology
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    • "The structures of compounds 1–4 were identified as (2R, 3R)-2′,3,5,6′,7-pentahydroxyflavanone [19], baicalein [20], neobaicalein [21], and wogonin [20], respectively, by analysis of 1D- and 2D-NMR data and comparisons with reported molecules (Figure 1(a)). The presence and identification of (2R, 3R)-2′,3,5,6′,7-pentahydroxyflavanone (1), baicalein (2), neobaicalein (3), and wogonin (4) in the extract of S. baicalensis was confirmed by cochromatography with their respective isolated compounds on HPLC (Figure 1(b)). "
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    ABSTRACT: Aims of study. The aim of the present study was to investigate whether an ethanol extract of Scutellaria baicalensis (ESB) relaxes penile corpus cavernosum muscle in organ bath experiments. Materials and methods. Changes in tension of cavernous smooth muscle strips were determined by penile strip chamber model and in penile perfusion model. Isolated endothelium-intact rabbit corpus cavernosum was precontracted with phenylephrine (PE) and then treated with ESB. Results. ESB relaxed penile smooth muscle in a dose-dependent manner, and this was inhibited by pre-treatment with N(G)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthase inhibitor, and 1H-[1, 2, 4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ), a soluble guanylyl cyclase (sGC) inhibitor. ESB-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA), a nonselective K(+) channel blocker, and charybdotoxin, a selective Ca(2+)-dependent K(+) channel inhibitor. ESB increased the cGMP levels of rabbit corpus cavernosum in a concentration-dependent manner without changes in cAMP levels. In a perfusion model of penile tissue, ESB also relaxed penile corpus cavernosum smooth muscle in a dose-dependent manner. Conclusion. Taken together, these results suggest that ESB relaxed rabbit cavernous smooth muscle via the NO/cGMP system and Ca(2+)-sensitive K(+) channels in the corpus cavernosum.
    Full-text · Article · Jan 2012 · Evidence-based Complementary and Alternative Medicine
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