Novel asymmetric total syntheses of (R)-(−)-pyridindolol, (R)-(−)-pyridindolol K1, and (R)-(−)-pyridindolol K2 via a mild one-pot aromatization of N-tosyl-tetrahydro-β-carboline with (S)-2,3-O-isopropylidene-l-glyceraldehyde as the source of chirality

Novel total syntheses of (R)-(−)-pyridindolol 1, (R)-(−)-pyridindolol K1 2, and (R)-(−)-pyridindolol K2 3 are described. By using l-tryptophan methyl ester and (S)-2,3-O-isopropylidene-l-glyceraldehyde as the starting materials, (R)-(−)-pyridindolol 1, (R)-(−)-pyridindolol K1 2, and (R)-(−)-pyridindolol K2 3 were synthesized in 5–7 steps in 66%, 41%, and 55% overall yields, respectively. The characteristic step of the total syntheses is a mild one-pot aromatization of N-tosyl-1,2,3,4-tetrahydro-β-carboline (N-Ts-THBC), which was obtained via Pictet–Spengler reaction of l-tryptophan methyl ester with (S)-2,3-O-isopropylidene-l-glyceraldehyde, and subsequent N-tosylation.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(R)-(−)-PyridindololC14H14N2O3[α]D20=-46.7 (c 0.5, MeOH)Source of chirality: l-ascorbic acidAbsolute configuration: (R)

(R)-(−)-Pyridindolol K1C18H18N2O5[α]D20=-13.6 (c 0.2, MeOH)Source of chirality: l-ascorbic acidAbsolute configuration: (R)

(R)-(−)-Pyridindolol K2C16H16N2O4[α]D20=-32.5 (c 0.3, MeOH)Source of chirality: l-ascorbic acidAbsolute configuration: (R)

Methyl (R)-1-(2,2-dimethyl-1,3-dioxolan-4-yl)-9H-pyrido[3,4-b]indole-3-carboxylateC18H18N2O4[α]D20=-14.2 (c 1.0, CHCl3)Source of chirality: l-ascorbic acidAbsolute configuration: (R)

(R)-(1-(2,2-Dimethyl-1,3-dioxolan-4-yl)-9H-pyrido[3,4-b]indol-3-yl)methanolC17H18N2O3[α]D20=-5.0 (c 0.4, CHCl3)Source of chirality: l-ascorbic acidAbsolute configuration: (R)

(R)-(1-(2,2-Dimethyl-1,3-dioxolan-4-yl)-9H-pyrido[3,4-b]indol-3-yl)methyl acetateC19H20N2O4[α]D20=-9.3 (c 0.6, CHCl3)Source of chirality: l-ascorbic acidAbsolute configuration: (R)