Heteroatom Chemistry. 2018;e21412. wileyonlinelibrary.com/journal/hc | 1 of 12 https://doi.org/10.1002/hc.21412 © 2018 Wiley Periodicals, Inc. 1 | INTRODUCTION The design and synthesis of desired and tolerable methods to attain complex molecules from appropriate starting materi- als are still challenging work for lots of scientific areas such as modern synthetic and medicinal chemistry. The methods which include synthesis of compounds containing nitrogen and oxygen are of growing importance due to the importance of some biological activities. [1a–c] Some important heterocy- clic compounds such as antituberculosis agent 1 (PA-824), antibiotic, sold under the trade name Levaquin 2, and acorta- tarin A 3 which is an inhibitor for the production of reactive oxygen species (ROS) [2] include oxazine cores (Figure 1). In a few decades, tremendous efforts have been de- voted to the development of new, efficient, atom- economic, and no-catalyst methods to achieve important heterobicyclic molecules. [3b–e] One of these protocol cov- ers 1,4-oxazine rings. There have been some synthetic methods for 1,4-oxazines and its bicyclic derivatives in the literature. Kerwin and coworkers have developed Received: 18 November 2017 | Revised: 26 January 2018 | DOI: 10.1002/hc.21412 RESEARCH ARTICLE An easy synthetic protocol for imidazo-1,4-oxazines and evaluation of their toxicities Burak Kuzu 1,2 | Hasan Genç 3 | Mehmet Taşpinar 4 | Meltem Tan 1,2 | Nurettin Menges 1,2 Contract grant sponsor: Scientific and Technological Research Council of Turkey. Contract grant number: 115Z894. Contract grant sponsor: Van Yüzüncü Yil University Coordinator of Scientific Research Projects. Contract grant number: TAP-2016-5610. Contract grant number: TAP-2017-6092. 1 Pharmaceutical Chemistry Section, Faculty of Pharmacy, Van Yüzüncü Yil University, Van, Turkey 2 YYU TEKNOKENT, R&D Lab. SAFF Chemical Reagent, Van, Turkey 3 Faculty of Education, Van Yüzüncü Yıl University, Van, Turkey 4 School of Medicine, Van Yüzüncü Yil University, Van, Turkey Correspondence Nurettin Menges and Meltem Tan, Pharmaceutical Chemistry Section, Faculty of Pharmacy, Van Yüzüncü Yil University, Van, Turkey. Emails: nurettinmenges@yyu.edu.tr (N.M.); meltemtan@yyu.edu.tr (M.T.) Funding information YYU-BAP, Grant/Award Number: TAP-2016-5610 and TAP-2017-6092; TÜBİTAK, Grant/Award Number: 115Z894 Abstract Imidazo-1,5-alkynyl alcohol derivatives were synthesized, and they were cyclized to imidazo-1,4-oxazines by means of cesium carbonate. Propargyl-allene isomerization was examined, and the reaction mechanism was proposed. Moreover, cytotoxicity of synthesized molecules against LN405 cell lines was investigated by means of structure-activity relationship (SAR). With SAR study, toxicities of some functional groups have been shown. In addition, two lead compounds were tested against DNA damaging. KEYWORDS allene, COMET, cyclization of alkyne, heterocyclic compounds, SAR