| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1346936 | Tetrahedron: Asymmetry | 2009 | 7 Pages |
The first synthesis of tadalafil 1 (Cialis) from l-tryptophan is described. The title compound 1 was synthesized via seven steps from l-tryptophan methyl ester hydrochloride in 42.3% overall yield. Two characteristic steps involved in this synthesis are the base-catalyzed epimerization of the C-3 position of (1S,3S)-1,2,3-trisubstituted-tetrahydro-β-carboline 3a and the acid-catalyzed epimerization of the C-1 position of (1S,3R)-1,3-disubstituted-tetrahydro-β-carboline 5. The (S)-configurations at C-1 and C-3 were inverted to (R)-configurations during the epimerization reactions. The base-catalyzed epimerization of C-3 of (1S,3S)-1,2,3-trisubstituted-tetrahydro-β-carbolines 3a–3e was also studied in detail.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
(1S,3S)-Methyl1-(benzo[d][1,3]dioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylateC20H18N2O4[α]D20=-25 (c 1.2, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3S)
(1S,3S)-2-Benzyl 3-methyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2,3-dicarboxylateC28H24N2O6[α]D20=+115 (c 1.5, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3S)
(1S,3S)-2-Ethyl 3-methyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2,3-dicarboxylateC23H22N2O6[α]D20=+132 (c 0.3, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3S)
(1S,3S)-2-Isobutyl 3-methyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2,3-dicarboxylateC25H26N2O6[α]D20=+131 (c 0.2, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3S)
(1S,3S)-3-Methyl 2-phenyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2,3-dicarboxylateC27H22N2O6[α]D20=+116 (c 0.3, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3S)
(1S,3S)-2-t-Butyl 3-methyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2,3-dicarboxylateC25H26N2O6[α]D20=+122 (c 1.2, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3S)
(1S,3R)-2-Benzyl 3-methyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2,3-dicarboxylateC28H24N2O6[α]D20=+41 (c 0.4, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3R)
(1S,3R)-2-Ethyl 3-methyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2,3-dicarboxylateC23H22N2O6[α]D20=+49 (c 0.4, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3R)
(1S,3R)-2-Isobutyl 3-methyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2,3-dicarboxylateC25H26N2O6[α]D20=+55 (c 0.2, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3R)
(1S,3R)-3-Methyl 2-phenyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2,3-dicarboxylateC27H22N2O6[α]D20=+89 (c 0.7, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3R)
(1S,3R)-2-t-Butyl 3-methyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2,3-dicarboxylateC25H26N2O6[α]D20=+42 (c 0.6, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3R)
(1S,3R)-Methyl 1-(benzo[d][1,3]dioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylateC20H18N2O4[α]D20=+33 (c 1.0, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1S,3R)
(1R,3R)-Methyl 1-(benzo[d][1,3]dioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylateC20H18N2O4[α]D20=+25 (c 0.9, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1R,3R)
(1R,3R)-Methyl 1-(benzo[d][1,3]dioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylateC22H19ClN2O5[α]D20=-126 (c 1.2, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1R,3R)
(6R,12aR)-6-(Benzo[d][1,3]dioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methylpyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dioneC22H19N3O4[α]D20=+71 (c 1.2, CHCl3)Source of chirality: l-tryptophanAbsolute configuration: (1R,3R)
