Site-selective synthesis of acacetin and genkwanin through lipase-catalyzed deacetylation of apigenin 5,7-diacetate and subsequent methylation

Rie Fujita, Susanta Mandal, Kengo Hanaya, Mitsuru Shoji, Shuhei Higashibayashi, Takeshi Sugai

Research output: Contribution to journalArticle

Abstract

Candida antarctica lipase B-catalyzed deacetylation proceeded with high site-selectivity on the C-4′ acetyl group in apigenin triacetate to give apigenin 5,7-diacetate. Methylation of the liberated hydroxy group with the combination of trimethyloxonium tetrafluoroborate (Meerwein reagent) and 1,8-bis(dimethylamino)naphthalene (proton sponge) in CH2Cl2 proceeded in a quantitative manner to give the product methylated at the C-4′ hydroxy group (acacetin 5,7-diacetate). Even with the same precursor, a different methylation product at the C-7 hydroxy group (genkwanin 4′,5-diacetate) was obtained in 86% yield by applying iodomethane and Cs2CO3 in dimethyl sulfoxide (DMSO). The methylated products were deprotected to form acacetin and genkwanin. We inferred that the latter unexpected methylation was ascribable to the intermolecular migration of an acetyl group from C-7 to C-4′. DFT calculations indicated that the C-7 phenoxide ion was 12.6 kJ/mol more stable than the initially formed C-4′ phenoxide ion.

Original languageEnglish
Pages (from-to)638-648
Number of pages11
JournalHeterocycles
Volume99
Issue number1
DOIs
Publication statusPublished - 2019 Jan 1

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Apigenin
Methylation
Lipase
Ions
Porifera
Dimethyl Sulfoxide
Discrete Fourier transforms
Protons
acacetin
genkwanin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmacology
  • Organic Chemistry

Cite this

Site-selective synthesis of acacetin and genkwanin through lipase-catalyzed deacetylation of apigenin 5,7-diacetate and subsequent methylation. / Fujita, Rie; Mandal, Susanta; Hanaya, Kengo; Shoji, Mitsuru; Higashibayashi, Shuhei; Sugai, Takeshi.

In: Heterocycles, Vol. 99, No. 1, 01.01.2019, p. 638-648.

Research output: Contribution to journalArticle

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AU - Higashibayashi, Shuhei

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