Total syntheses of beta-carboline alkaloids, (R)-(-)-pyridindolol K1, (R)-(-)-pyridindolol K2, and (R)-(-)-pyridindolol.
The total syntheses of beta-carboline alkaloids, (R)-(-)-pyridindolols (1, 5, and 6) are described. The two key steps involved are (1) a thermal electrocyclic reaction of the 3-alkenylindole-2-aldoxime 10 and (2) a thermal cyclization of 3-alkynylindole-2-aldoxime 11 to construct the beta-carboline N-oxides 8, which upon heating with acetic anhydride and sequential treatment with trifluoromethanesulfonic anhydride gave the triflates 18. The Stille coupling reaction of 18 with vinylstannane, followed by cleavage of MOM ether, afforded the 1-ethenyl-3-hydroxymethyl-beta-carboline (7a). Subsequent acetylation of 7a yielded the acetate 7b, which was subjected to the Sharpless asymmetric 1,2-dihydroxylation by AD-mix-beta to produce (R)-(-)-pyridindolol K2 (6). Selective acetylation of 6 was effected by Ac(2)O and collidine to form (R)-(-)-pyridindolol K1 (5). By contrast, hydrolysis of 6 provided (R)-(-)-pyridindolol (1).
Kanekiyo
N
N
Graduate School of Pharmacy and Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan.
Kuwada
T
T
Choshi
T
T
Nobuhiro
J
J
Hibino
S
S
D002243:Carbolines / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D013237:Stereoisomerism
D002243:Carbolines; D007202:Indicators and Reagents; C106432:pyridindolol K1; C106433:pyridindolol K2; C010774:pyridindolol