A series of diterpenoid 1,3-aminoalcohol derivatives was synthesised from isosteviol through stereoselective transformations. Isosteviol was obtained via acid-catalysed hydrolysis and rearrangement of natural stevioside and subsequently converted to the key methyl ester intermediate. A 1,3-aminoalcohol library was then constructed by reductive amination of the 3-hydroxyaldehyde intermediate derived from isosteviol in a two-step process. To evaluate the influence of the carboxylate ester at position 4, analogues bearing a free carboxylic acid, benzyl ester, or acryloyl ester were prepared as extended derivatives, building on our previous findings in this area. The antiproliferative activity of the compounds was assessed against human tumour cell lines (A2780, HeLa, MCF-7, and MDA-MB-231). In this preliminary investigation, the 1,3-aminoalcohol moiety featuring N-benzyl or (1H-imidazol-1-yl)-propyl substitution combined with a benzyl ester group appeared critical for consistent antiproliferative effects. These findings provide a promising foundation for further functionalisation aimed at developing more potent antiproliferative diterpenes.
