The total synthesis of (±)-lycoramine. Part II

Abstract

An alternative and improved synthetic pathway to lycoramine involving construction of the skeleton in the order ring A, ring B, ring C, ring D, is described. 2,3-Dimethoxybenzaldehyde (I) was converted into 2,3-dimethoxyphenylacetone (III), which was condensed with acrylonitrile, to give γ-acetyl-γ-(2,3-dimethoxyphenyl)pimelonitrile (IV). The corresponding ester (VII) was cyclised to 1-(2,3-dimethoxephenyl)-2,4-dioxocyclohexanepropionate (IX). Treatment of its monoacetal (X) with lithium aliminium hydride followed by oxalic acid yielded 4a-(2,3-dimethoxyphenyl)-7-oxoperhydrobenzo[b]pyran (XIV). This was converted into 1,2,3,4,4a,9b-hexahydro-6-hydroxy-9b-(3-iodopropyl)-3-oxodibenzofuran (XV) with hydriodic acid. 9-Acetoxy-1,2,8,9,10,11-hexahydro-6-methoxy-3H,7aH-benzo[b]naphtho[1,8-cd]furan-3-one (XXV), which was obtained in seven steps from (XV), was treated with hydrazoic acid to yield a mixture of isomeric lactams [(XXIX) and (XXX)] which were separated, and the required one (XXX) was N-methylated and treated with lithium aluminium hydride to furnish (±)-lycoramine, overall yield 0·67%.