Journal of the Chemical Society C Organic · 1968 · 15 citations · 0 references
PharmacyChemistryMedicinal ChemistryBioorganic ChemistryOrganic ChemistrySynthetic Medicinal ChemistryAlkaloid BiosynthesisHeterocycle SynthesisHeterocyclic ChemistryOrganic SynthesisAlkaloid Skeleton FormationDieckmann CyclizationLycorine BiosynthesisNatural Product Total SynthesisRing-forming ReactionsTotal Synthesis-derived Analogues
A stepwise synthesis of (±)-lycoramine, an alkaloid of the Amaryllidaceae, has been achieved by initial construction of rings A and B followed by formation of ring C, and finally establishment of ring D. The Dieckmann cyclisation of dimethyl γ-cyano-γ-(3-ethoxy-2-methoxyphenyl)pimelate (VIII), obtained from 3-ethoxy-2-hydroxybenzaldehyde (III) in five steps, gave methyl 5-cyano-5-(3-ethoxy-2-methoxyphenyl)-2-oxocyclohexanecarboxylate (IX) which was converted into 4-acetoxy-7′-ethoxy-1′,2′-dihydro-8′-methoxyspiro[cyclohexane-1,1′-naphthalen]-4′(3′H)-one (XXII) by a sequence of reactions including the Wittig and the Friedel-Crafts. The Schmidt reaction on this compound gave two isomeric lactams (XXV) and (XXVI), the latter of which was N-methylated, deacetylated, and oxidised to furnish 7-ethoxy-2,3,4,5-tetrahydro-6-methoxy-2-methyl-1H-spiro[2-benzazepine-5,1′-cylcohexane]-1,4′-dione (XXX) which could also be derived from natural lycoramine. By use of this relay substance as a key intermediate, (±)-lycoramine was synthesised.