Synthesis of oroxylin A starting from naturally abundant baicalin

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Abstract

– A new approach to oroxylin A, a monomethylated trihydroxyflavone, is described. The starting material was baicalin, a representative naturally abundant flavonoid glucuronide. First, conditions for the cleavage of the glycosidic bond were established, using a mixture of water and conc. sulfuric acid (5:2) at 121 °C for 40 min. The hydrolysis was performed in a high-pressure steam sterilizer so that the temperature and reaction time were precisely controlled. Subsequent acetylation of the crude material furnished baicalein 6,7-diacetate on a preparative scale and in a reproducible manner. Next, the C-7 position was protected site-selectively with a methoxymethyl (MOM) group, taking advantage of an unexpected sequential migration of the two acetyl groups among the C-5, C-6, and C-7 positions under basic conditions. The removal of the two remaining acetyl groups followed by site-selective methylation of the C-6 position furnished 5-hydroxy-6-methoxy-7-methoxymethoxyflavone (oroxylin A C-7 MOM ether). Finally, by the deprotection of the MOM ether, oroxylin A was obtained in 6 total steps and 62% overall yield from baicalin.

Original languageEnglish
Pages (from-to)1165-1174
Number of pages10
JournalHeterocycles
Volume97
Issue number2
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Ether
Sterilizers
Acetylation
Methylation
Glucuronides
Steam
Flavonoids
Hydrolysis
Pressure
Temperature
Water
5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
baicalin
sulfuric acid
baicalein

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmacology
  • Organic Chemistry

Cite this

Synthesis of oroxylin A starting from naturally abundant baicalin. / Fujita, Rie; Hanaya, Kengo; Higashibayashi, Shuhei; Sugai, Takeshi.

In: Heterocycles, Vol. 97, No. 2, 01.01.2018, p. 1165-1174.

Research output: Contribution to journalArticle

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