Synthesis of 4-acetylisocoumarin: first total syntheses of AGI-7 and sescandelin.
A practical synthetic route to 4-acetylisocoumarins and the first total synthesis of AGI-7 (5) and sescandelin (4) are described. The readily available homophthalate 8 was transformed to the vinylogous amide ester 13 in high overall yield. Upon treatment of 13 with refluxing aqueous formic acid, the desired 4-acetylisocoumarin (5) and its regioisomer 3-methyl-4-formylisocoumarin (17) were produced in a 3:1 ratio. After separation of the desired product (5) from the unwanted minor isomer, the enantioselective reduction of AGI-7 by borane in the presence of Corey's (S)-oxazaborolidine reagent afforded (+)-sescandelin (4) with a 93% ee.
Kim
Sanghee
S
Natural Products Research Institute, Seoul National University, 28 Yungun, Jongro, Seoul 110-460, Korea. pennkim@snu.ac.kr
Fan
Gao-jun
GJ
Lee
Jaekwang
J
Lee
Jung Joon
JJ
Kim
Deukjoon
D
D001685:Biological Factors / Q000138:chemical synthesis*; D002384:Catalysis; D002855:Chromatography, Thin Layer; D020650:Combinatorial Chemistry Techniques; D003374:Coumarins / Q000138:chemical synthesis*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism
C433014:AGI-7 coumarin; D001685:Biological Factors; D003374:Coumarins; C433015:sescandelin