First Total Syntheses of (±)-Isopiline, (±)-Preocoteine, (±)-Oureguattidine and (±)-3-Methoxynordomesticine and the Biological Activities of (±)-3-Methoxynordomesticine

A convenient and economical synthesis of 4-hydroxy-2,3-dimethoxybenzaldehyde has been developed. This was used as the starting material for the first total syntheses of (+/-)-isopiline, (+/-)-preocoteine, (+/-)-oureguattidine and (+/-)-3-methoxynordomesticine in which the key step involved formation of ring C of the aporphines by a radical-initiated cyclisation. Although (+/-)-3-methoxynordomesticine possesses weak antimicrobial activity, it inhibits the production of nitric oxide (NO), prostaglandin (PG)E-2, tumor necrosis factor (TNF)-alpha interleukin (IL)-1 beta and IL-6 and the expression of inducible nitric oxide synthase (iNOS) and cycloxygenase (COX)-2 in macrophages stimulated with LPS in vitro.