Lipase-catalyzed asymmetric synthesis of desprenyl-carquinostatin A and descycloavandulyl-lavanduquinocin.
An asymmetric synthesis of the core carbazole structure, 6-desprenyl-carquinostatin 3 and 6-descycloavandulyl-lavanduquinocin 3, toward a total synthesis of carquinostatin A (1) and lavanduquinocin (2), has been established. Lipase QLM (Meito) catalyzed enantioselective acetylation of the racemic alcohol 6 gave the (-)-acetate 7 and the (+)-alcohol 6 with high enantioselectivity. The absolute stereochemistry of the (-)- and (+)-alcohol 6 have been determined to be R- and S-configurations, respectively, by the advanced Mosher method. In the same manner, the (-)-acetate 13 and the (+)-alcohol 12 have been obtained from the racemic alcohol 12. The (R)-(-)-acetate 13, derived from the (R)-(-)-acetate 7, was the same as the (-)-acetate 13, which has been determined to be (R)-configuration. Oxidation of the (R)-(-)-acetate 13 followed by hydrolysis afforded (R)-(-)-6-desprenyl-carquinostatin [and (R)-(-)-6-descycloavandulyl-lavanduquinocin] 3. In addition, oxidation of the (S)-(+)-alcohol 12 provided (S)-(+)-3, which is the enantiomer of 6-desprenyl-carquinostatin A (R)-(-)-3.
Choshi
Tominari
T
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.
Uchida
Yoshinari
Y
Kubota
Yukiko
Y
Nobuhiro
Junko
J
Takeshita
Mitsuhiro
M
Hatano
Takushi
T
Hibino
Satoshi
S
D000107:Acetylation; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D006868:Hydrolysis; D008049:Lipase / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
C522656:6-desprenyl-carquinostatin A; D002227:Carbazoles; C113606:carquinostatin A; C095334:lavanduquinocin; D008049:Lipase