First Total Synthesis of N-(3-Guanidinopropyl)-2-(4-hydroxyphenyl)-2-oxoacetamide

The first total synthesis of the alpha-oxo amide-based natural product, N-(3-guanidinopropyl)-2-(4-hydroxyphenyl)-2-oxoacetamide (3), isolated from aqueous extracts of hydroid Campanularia sp., has been achieved. The alpha-oxo amide 12, prepared via the oxidative amidation of 1-[4-(benzyloxy)phenyl]-2,2-dibromoethanone (9a) with 4-{[(tert-butyl)(dimethyl)silyl]oxy}butan-1-amine (10a), has been used as the key intermediate in the total synthesis of 3 as HBr salt. On the way, an expeditious total synthesis of polyandrocarpamide C (2c), isolated from marine ascidian Polyandrocarpa sp., was carried out in four steps.