A novel mesoionic ring system: unusual cyclization of thio- and amino-acid derivatives of 6-azauracil Frederick J. Lakner, Haiji Xia, Azra Pervin, Jeffrey R. Hammaker, Kathy G. Jahangiri, Michael K. Dalton, Alexander Khvat, * Alexander Kiselyov and Alexandre V. Ivachtchenko ChemDiv Inc., 11558 Sorrento Valley Rd., Suite 5, San Diego, CA 92121, USA Received 21 March 2005; revised 3 June 2005; accepted 3 June 2005 Abstract—Novel mesoionic heterocyclic structures 8 havebeenobtainedviatheinternalcyclizationofthio-andamino-acidderiv- ativesof6-azauracil 7b–d.Thesecompoundsundergoring-openingreactionswithaminestoyieldtherespective6-azauracilamides (9) in good yields under microwave irradiation. Ó 2005 Elsevier Ltd. All rights reserved. 6-Azauracil ring system is well represented in both chemical and biological literature. Compounds (Fig. 1) containing this template were described to possess anti- cancer (1), 1 anti-depressant/hypnotic (1), 2 antiallergic/ antiasthmatic (2), 3 anxiolitic/antidepressant (3), 4 and anticoccidial properties (4). 5 Similar compounds con- taining acetamide appendages 5 (teomorfolin) 6 and 6 7 (Fig.2)displayhypolipidemicandnon-opioidanalgesic activities, respectively. In our ongoing effort to identify templates for the syn- thesis of compound libraries biased against specific bio- logical targets, 8 we investigated the synthetic potential of carboxylic acids 7a–d (Fig. 3) available from 5-bromoazauracil. 9 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.06.032 Keywords: Mesoionic structures; X-ray analysis; 6-Azauracil; Micro- wave; Amidation reaction. * Corresponding author. Tel.: +1 8587944860; fax: +1 8587944931; e-mail: ak@chemdiv.com HN N N O O CN Cl Cl F HN N N O O N N N N HN N N O O O OH OH HO HN N N O O S N N Cl Cl Cl 1 2 3 4 Figure 1. N N S N O O O O N N N N O N O O O + 5 6 Figure 2. HN N H N O O S O OH R HN N H N O O N O OH HN N H N O O N OH O 7a 7b, R = H 7c, R = Et 7d Figure 3. Tetrahedron Letters 46 (2005) 5325–5328 Tetrahedron Letters