The first total synthesis of kwakhurin, a characteristic component of a rejuvenating plant, "kwao keur": toward an efficient synthetic route to phytoestrogenic isoflavones.
A convergent synthesis of kwakhurin (5), a characteristic estrogen-like isoflavone of Pueraria mirifica(Leguminosae), is described. Isoflavone skeleton 31 was constructed by Suzuki-Miyaura coupling of 3-bromochromone 26 (AC-ring) and arylboronic acid 30 (B-ring) in the presence of TBAB as an additive. Microwave-assisted coupling was also examined, but did not improve the yield. Baeyer-Villiger oxidation, followed by propargylation and reduction afforded 1,1-dimethylallyl ether 37. 6'-Prenylisoflavone 34 was obtained in high yield by Claisen rearrangement of 37 in N,N-diethylaniline. On the other hand, 1,3-rearrangement of prenyl ether 33 with clay gave 34 in poor yield. Successive methylation of 34 and deprotection yielded the target kwakhurin (5) in 12% overall yield from 2,4-dihydroxybenzaldehyde (23).
Ito
Fumihiro
F
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan.
Iwasaki
Misako
M
Watanabe
Toshiko
T
Ishikawa
Tsutomu
T
Higuchi
Yoshihiro
Y
D001897:Boronic Acids / Q000737:chemistry; D002867:Chromones / Q000737:chemistry; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry; D007529:Isoflavones / Q000138:chemical synthesis* / Q000737:chemistry; D008745:Methylation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D048789:Phytoestrogens / Q000138:chemical synthesis* / Q000737:chemistry; D029908:Pueraria / Q000737:chemistry*
D001897:Boronic Acids; D002867:Chromones; D006575:Heterocyclic Compounds, 3-Ring; D007529:Isoflavones; D048789:Phytoestrogens; C511898:kwakhurin