Stereoselective Synthesis and Cytoselective Toxicity of Monoterpene-Fused 2-Imino-1,3-thiazines

Molecules

Zsolt Szakonyi¹  István Zupkó²  Reijo Sillanpää³  Ferenc Fülöp¹ 

[1] Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, H-6720 Szeged, Hungary;Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary; E-Mail:;Department of Chemistry, University of Jyväskylä, P.O. Box 35, 40351 Jyväskylä, Finland; E-Mail:

关键词: monoterpene;    1;    3-amino alcohol;    stereoselective;    CDI;    1;    3-thiazine;    antiproliferative;   

DOI  :  10.3390/molecules191015918

来源: mdpi

【 摘 要 】

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).

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.