Stereoselective synthesis of (+)-isoindolo-β-carboline

Starting from homophthalic anhydride and (S)-tryptophan, the stereoselective synthesis of (+)-isoindolo-β-carboline has been described via the corresponding homophthalimide, its chemoselective oxidative ring contraction, and the intramolecular dehydrative ring closure followed by a geometry-specific demethoxycarbonylation.

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(S)-7-Oxo-6,7,11b,12-tetrahydro-5H-6a,12-diaza-(R)-indeno[1,2-a]fluorene-6-carboxylic acid methyl esterC20H16N2O3De ∼ 100%; ee >98%[α]D20=+101.6 (c 1.0, CHCl3)Source of chirality: (S)-tryptophanAbsolute configuration: (S,R)

(S)-Methyl 5,7,8,13b-Tetrahydro-5-oxo-13H-13b-methoxycarbonyl-(S)-indolo[2,3-c]isoindolo[2,1-a] pyridine-7-carboxylateC22H18N2O5Ee ∼ 100%[α]D20=-43.6 (c 1.0, CHCl3)Source of chirality: (S)-tryptophanAbsolute configuration: (S,S)

(R)-Methyl 5,7,8,13b-Tetrahydro-5-oxo-13H-13b-methoxycarbonyl-(S)-indolo[2,3-c]isoindolo[2,1-a]pyridine-7-carboxylateC22H18N2O5Ee ∼ 100%[α]D30=+63.5 (c 2.4, CHCl3)Source of chirality: (S)-tryptophanAbsolute configuration: (S,R)