Background: In the recent years the 2-imino-1,3-thiazine and 2-iminothiazolidine ring systems can be
found as moieties in biologically relevant compounds, including BACE1 inhibitors, or cannabinoid receptor agonists,
while monoterpene-based 2-imino-1,3-thiazines, prepared from chiral 1,3-amino alcohols exhibiting pronounced
Methods: The antiproliferative activities of the prepared compounds were determined in vitro against a panel of
human adherent cancer cell lines including HeLa, MCF7 and A431 by MTT assay.
Results: Starting from pinane-, apopinane- and carane-based β-amino acid derivatives, 1,3-amino alcohols were
prepared via two-step syntheses. The reactions of the product 1,3-amino alcohols and aryl isothiocyanates yielded
ϒ-hydroxythioureas, which were transformed to monoterpene-fused 2-imino-1,3-oxazines via base-catalysed ring
closure. The antiproliferative activities of these 2-imino-1,3-oxazines were examined and the structure–activity
relationships were studied from the aspects of the type and stereochemistry of the monoterpene ring and the substituent
effects on the 1,3-oxazine ring system. The N-unsubstituted monoterpene-based derivatives exhibited
considerable antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF7 and
Conclusions: A mild and efficient method has been developed for the synthesis of 2-imino-1,3-oxazines by the
ring closure of thiourea adducts of 1,3-amino alcohols. The resulting 1,3-oxazines exert marked antiproliferative
action on a panel of human cancer cell lines.