Synthesis of a capillarisin sulfur-analogue possessing aldose reductase inhibitory activity by selective isopropylation.
We describe the synthesis of 2-[(4-hydroxyphenyl)thio]-7-isopropoxy-5,6-dimethoxy-4H-chromen-4-one 2 from 3,4,5-trimethoxyphenol 6 via the key intermediate, 3-iodo-7-isopropoxy-5,6-dimethoxy-4H-chromen-4-one 3. An important feature of this synthetic scheme involves selective alkylation, which can be achieved by two different routes. One route involves the selective isopropylation of a triacetate derivative 4 under basic conditions. The second route employs the selective demethylation of a trimethoxy derivative 5 under acidic conditions followed by isopropylation. The product of these alternative routes, compound 3, is then converted to a capillarisin sulfur analogue 2 in a one-pot reaction via the imidazolyl intermediate 22.
Igarashi
Yasushi
Y
Research Division, Tsumura & Co.; 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. igarashi_yasushi@mail.tsumura.co.jp
Kumazawa
Hiroaki
H
Ohshima
Toshihoro
T
Satomi
Hisanori
H
Terabayashi
Susumu
S
Takeda
Shuichi
S
Aburada
Masaki
M
Miyamoto
Ken-Ichi
K
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000478:Alkylation; D002839:Chromans / Q000138:chemical synthesis* / Q000494:pharmacology*; D002867:Chromones / Q000138:chemical synthesis* / Q000494:pharmacology*; D003640:Dealkylation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy
C504998:2-((4-hydroxyphenyl)thio)-7-isopropoxy-5,6-dimethoxy-4H-chromen-4-one; D002839:Chromans; D002867:Chromones; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; C011185:capillarisin; D000449:Aldehyde Reductase