Concise synthesis of anti-HIV-1 active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-Michael addition.
(-)-Quinine-catalyzed intramolecular oxo-Michael addition (IMA) of 7-hydroxy-5-methoxy-8-tigloylcoumarins was developed for the enantioselective construction of 2,3-dimethyl-4-chromanone systems in the context of the asymmetric synthesis of anti-HIV-1 active Calophyllum coumarins. Combination of the IMA and MgI(2)-assisted demethylation of the 5-methoxy group along with isomerization of the formed chromanone systems as key steps successfully led to the concise synthesis of (+)-inophyllum B and (+)-calanolide A, possible candidates for AIDS drugs. Further examination of the asymmetric IMA with cinchona alkaloids lacking a methoxy group on the quinoline skeleton suggested the influence of the methoxy substituent on stereoselectivity at the stereogenic centers of the chromanone systems.
Sekino
Etsuko
E
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan.
Kumamoto
Takuya
T
Tanaka
Tomohiro
T
Ikeda
Tomoko
T
Ishikawa
Tsutomu
T
D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D002384:Catalysis; D003374:Coumarins / Q000138:chemical synthesis*; D015394:Molecular Structure; D039681:Pyranocoumarins; D011803:Quinine / Q000737:chemistry*; D013237:Stereoisomerism
D019380:Anti-HIV Agents; D003374:Coumarins; D039681:Pyranocoumarins; C086091:inophyllum B; D011803:Quinine; C075959:calanolide A