Stereoselective synthesis and antiproliferative activity of monoterpene-fused 2-imino-1,3-oxazines

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Abstract

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 antiproliferative activity. 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 γ-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 A431). 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.

Original languageEnglish
Pages (from-to)612-619
Number of pages8
JournalCurrent Organic Synthesis
Volume14
Issue number4
DOIs
Publication statusPublished - Jun 1 2017

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Keywords

  • 1, 3-amino alcohol
  • 1, 3-oxazine
  • Antiproliferative
  • Asymmetric synthesis
  • Enantiopure chiral templates
  • Monoterpene

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

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