Total Syntheses of β-Carboline Alkaloids, (R)-(−)-Pyridindolol K1, (R)-(−)-Pyridindolol K2, and (R)-(−)-Pyridindolol

The total syntheses of β-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 β-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-β-carboline (7a). Subsequent acetylation of 7a yielded the acetate 7b, which was subjected to the Sharpless asymmetric 1,2-dihydroxylation by AD-mix-β to produce (R)-(−)-pyridindolol K2 (6). Selective acetylation of 6 was effected by Ac₂O and collidine to form (R)-(−)-pyridindolol K1 (5). By contrast, hydrolysis of 6 provided (R)-(−)-pyridindolol (1).