Convenient Synthesis of Wogonin, A Flavonoid Natural Product with Extensive Pharmacological Activity

Abstract

Wogonin (5,7-dihydroxy-8-methoxyflavone, 5), a flavonoid natural product first isolated from Scutellaria Radix, is well-known for its anti-inflammation, 1 anti-allergy, 2 anti-tumor 3 and anti-hepatitis B virus 4 properties. Owing to its extensive applications in medical treatment, researchers have developed several synthetic pathways to obtain this important natural product since the early part of the last century. 5, 6 The initial total syntheses of wogonin were based on the common synthetic approaches to flavonoids through Baker-Venkataraman rearrangement 6, 7 or intramolecular Wittig reaction. 8 However, neither of these two strategies was efficient for large scale production of the compound. Recently Huang et al. 9 reported a simplified synthesis of wogonin (5) and oroxylin A (6) from 3,4,5-trimethoxyphenol (1) and cinnamoyl chloride (2). As shown in Figure 1, the flavone nucleus was obtained from intermediate 4 wherein the two hydroxyl groups compete for the addition to the α,β-unsaturated ketone moiety. Evidently, the C 6 -OH is more active than C 2 -OH since the yield of oroxylin A was nearly double that of wogonin. Moreover, this synthetic route is not an ideal process for industrial production because the two products are difficult to separate.Prompted by this earlier report on the construction of the flavone nucleus, we launched our own studies, focusing on avoiding the undesired flavone derivative 6 in the total synthesis of pure wogonin (Figure 2). To avoid the competitive addition process while forming the flavone nucleus, we utilized intermediate 8 which has only one reactive position. Intermediate 8 was synthesized in >90% yield from 2,5-dimethoxybenzene-1,3-diol (7)

Wogonin induces cell cycle arrest and erythroid differentiation in imatinib-resistant K562 cells and primary CML cells

“…Wogonin (purity ≥99%) was synthesized and used in all experiments unless otherwise indicated[45]. The final concentration of dimethyl sulfoxide (DMSO) in all experiments was ≤0.01%, and cells treated with the highest concentration of DMSO were used as controls in the corresponding experiments.…”

Hybrid of DNA-targeting Chlorambucil with Pt(IV) Species to Reverse Drug Resistance

“…These findings indicated that compound 5 might induce higher level of caspase-dependent apoptosis than cisplatin in cisplatinresistant cancer cells. The CFA assay (CFA) is an extensively used and wellestablished method for testing chemotherapeutic agents in vitro (Li et al, 2009), reflecting the ability of chemotherapeutic agents to prevent the cell from dividing. To further detect the effect of cell proliferation inhibition of compound 5, we used the colony forming assay to compare the ability of compound 5 and cisplatin to prevent the proliferation of cisplatin-sensitive A549 and cisplatin-resistant A549/CDDP cancer cell lines.…”

A Practical and Efficient Approach to the Preparation of Bioactive Natural Product Wogonin

“…Three synthetic approaches toward 1 have been reported . Rao’s route in 1947 selected chrysin ( 2 ) as a starting material to obtain 1 through O7-benzylation, oxidation, methylation, and debenzylation (Scheme , Route A) .…”