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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Solid Phase Synthesis of Structurally Diverse1,2,5-Benzothiadiazepin-4-on-1,1-dioxidesKarel-Simon Slock, Jurgen Caroen, and Johan Van der EyckenLaboratory of Organic and Bioorganic Synthesis, Department of Organic Chemistry,Ghent University, 9000, Gent, BelgiumIntroductionIn modern drug research, a lot of attention goes out to so called “privileged structures”.This term, introduced by Evans et al., was used to describe small molecules that showaffinity for different therapeutic targets [1]. Using these molecules as a scaffold anddecorating them with diverse side chains has proven to be a successful strategy in thefinding of new drug candidates [2]. Therefore, our laboratory has shown a lot of interest inthe search for new privileged structures.A class of heterocyclic scaffolds currently under investigation are the 1,2,5-benzothiadiazepin-4-on-1,1-dioxides 1, which are closely related to the well known 1,4-benzodiazepin-2,5-diones 2. Although biological activity has already been reported withsome benzothiadiazepines [3], these structures remain rather unexplored.R 1R 2SO O ONONHNHNHO12We would like to present a new solid phase synthesis of some structurally diverse1,2,5-benzothiadiazepin-4-on-1,1-dioxides using commercial or easy to synthesize buildingblocks, as shown in the Figure 1.OHWang resind)f)R 3a), b)OOHNHO2c)NO SR 3R 1RO 1O NO 267O RO O R 22RS NN3 g)O SR 3R 1O R 2O R 2RN3e)NO SO SR 3RO 1O NO 2RO 1O NH 28 9RO 1O HN R 4 NOR 4134101a) Fmoc-AA-OH, DIC, DMAP, CH 2 Cl 2 b) 20% 4-methylpiperidine in DMF, 2x10min c) ortho-nosylchloride,collidine, CH 2 Cl 2, 2x1h d) R 2 -OH, DIAD, PPh 3 , DCE, 2x1h e) CrCl 2 , DMF/MeOH 9/1, 2x1h f) R 4 -CHO,NaBH(OAc) 3 , 1% AcOH in DCE, 2x24h g) 1M LiOtBu in THF, 1hFig. 1. a) Fmoc-AA-OH, DIC, DMAP, CH 2 Cl 2 , b) 20% 4 methylpiperidine in DMF, 2x10min, c) ortho-nosylchloride, collidine, CH 2 Cl 2 , 2x1 hr, d) R 2 -OH, DIAD, PPh 3 , DCE, 2x1h,e) CrCl 2 , DMF/MeOH 9/1, 2x1h, f) R 4 -CHO, NaBH(OAc) 3 , 1% AcOH in DCE, 2x24h, g)1M LiOtBu in THF, 1h.