| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1347705 | Tetrahedron: Asymmetry | 2008 | 8 Pages |
The acid-catalyzed Pictet–Spengler reaction of d-tryptophan methyl ester with piperonal in acetic acid has been reported, the best stereoselectivity (cis/trans = 92:8) was obtained with benzoic acid as the catalyst. The Pictet–Spengler reaction of d-tryptophan methyl ester hydrochloride with piperonal in various solvents has been extensively studied, the solvent-dependence of stereoselectivities could be principally attributed to the solubility-difference between cis and trans products 5-HCl in the used solvent, the best stereoselectivity (cis/trans = 99:1) was obtained using nitromethane or acetonitrile as the solvent. A base-catalyzed epimerization at 12a-position of Cialis 1 (tadalafil) in a DMSO-containing solvent was also exploited. Cialis, 12a-epi-Cialis 2, deuterium-labeled 3,3,12a-d3-Cialis 3, and 3,3,12a-d3-12a-epi-Cialis 4 were efficiently synthesized from d-tryptophan methyl ester hydrochloride.
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(1R,3R)-1-(3,4-Methylenedioxyphenyl)-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic methyl esterC20H18N2O4[α]D20=+25.2 (c 1.0, CHCl3)Source of chirality: d-tryptophanAbsolute configuration: (1R,3R)
(1S,3R)-1-(3,4-Methylenedioxyphenyl)-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic methyl esterC20H18N2O4[α]D20=+33.1 (c 1.0, CHCl3)Source of chirality: d-tryptophanAbsolute configuration: (1S,3R)
(1R,3R)-1-(3,4-Methylenedioxyphenyl)-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic methyl ester hydrochlorideC20H19N2O4Cl[α]D20=+92.9 (c 1.1, MeOH)Source of chirality: d-tryptophanAbsolute configuration: (1R,3R)
(1R,3R)-1-(3,4-Methylenedioxyphenyl)-2-chloroacetyl-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic methyl esterC22H19N2O5Cl[α]D20=-126.0 (c 1.1, CHCl3)Source of chirality: d-tryptophanAbsolute configuration: (1R,3R)
(6R,12aR)-2,3,6,7,12,12a-Hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyrazino-[2′,1′:6,1]pyrido[3,4-b]indole-1,4-dioneC22H19N3O4[α]D20=+71.5 (c 1.0, CHCl3)Source of chirality: d-tryptophanAbsolute configuration: (6R,12aR)
(6R,12aS)-2,3,6,7,12,12a-Hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyrazino-[2′,1′:6,1]pyrido[3,4-b]indole-1,4-dioneC22H19N3O4[α]D20=-303.1 (c 1.2, CHCl3)Source of chirality: d-tryptophanAbsolute configuration: (6R,12aS)
(6R,12aR)-2,3,6,7,12,12a-Hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-3,3,12a-trideutero-pyrazino-[2′,1′:6,1]pyrido[3,4-b]indole-1,4-dioneC22H16D3N3O4[α]D20=+87.1 (c 1.0, CHCl3)Source of chirality: d-tryptophanAbsolute configuration: (6R,12aR)
(6R,12aS)-2,3,6,7,12,12a-Hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-3,3,12a-trideutero-pyrazino-[2′,1′:6,1]pyrido[3,4-b]indole-1,4-dioneC22H16D3N3O4[α]D20=-268.0 (c 1.2, CHCl3)Source of chirality: d-tryptophanAbsolute configuration: (6R,12aS)
