title: Stereoselective synthesis and cytoselective toxicity of monoterpene-fused 2-imino-1,3-thiazines.
abstract: Starting from pinane-, apopinane- and carane-based 1,3-amino alcohols obtained from monoterpene-based β-amino acids, a library of monoterpene-fused 2-imino-1,3-thiazines as main products and 2-thioxo-1,3-oxazines as side-products were prepared via two- or three-step syntheses. When thiourea adducts prepared from 1,3-amino alcohols and aryl isothiocyanates were reacted with CDI under mild conditions, O-imidazolylcarbonyl intermediates were isolated which could be transformed to the desired 1,3-thiazines under microwave conditions. 1,3-Thiazines and 2-thioxo-1,3-oxazine side-products could also be prepared in one-step reactions through the application of CDI and microwave irradiation. The ring-closure process was extended to cycloalkane-based γ-hydroxythioureas. The carane- and apopinane-based derivatives exhibited marked antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, A2780, MCF7 and A431).
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, H-6720 Szeged, Hungary. szakonyi@pharm.u-szeged.hu.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szakonyi
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. zupko@pharm.u-szeged.hu.
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
authors.affiliation: Department of Chemistry, University of Jyväskylä, P.O. Box 35, 40351 Jyväskylä, Finland. e.reijo.j.sillanpaa@jyu.fi.
authors.forename: Reijo
authors.initials: R
authors.lastname: Sillanpää
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, H-6720 Szeged, Hungary. fulop@pharm.u-szeged.hu.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fülöp
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008968:Molecular Conformation; D039821:Monoterpenes / Q000737:chemistry*; D013237:Stereoisomerism; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D039821:Monoterpenes; D013843:Thiazines