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Show Le- Justin Litchfield Senior Chemistry litch@chem.utah.edu Faculty Sponsor: Matthew S. Sigman Dept. of Chemistry Sigman@chem.utah.edu STUDIES TOWARD A COMBINATORIAL SYNTHESIS OF AGROBACTIN AND ANALOGS Development of a novel, modular, and convergent synthesis of agrobactin has been underway. Motivation behind this project is the potential bioactivity of the natural product agrobactin. Agrobactin is topologically homologous to -Conotoxin PVIIA, which binds the Shaker K+ channel, and so it is expected that agrobactin will exhibit similar bioactivity. The method being developed is superior to previous syntheses because of need for protecting groups is avoided. Additionally, the synthesis is modular and facilitates synthesis of analogs. The synthetic route being pursued has proven viable for the synthesis of a model compound. Synthesis of the agrobactin analog began with preparation of 3 from salicylic acid 1 and amino alcohol 2, followed by hydrolysis to give 4. The triamine backbone 7 was formed using activated salicylic acid 5 and the commercially available triamine 6. Finally, amine 7 and acid 5 were coupled using pivalloyl chloride, giving the desired agrobactin analog 8. Work is currently underway to apply this synthetic scheme to the synthesis of agrobactin and analogs. OH HO O A. GBzl H0 NH2 2 OBzl OH O Y&-- O O \ HjN NH2 ,-Q_, ^ O N J/ OH HO N H OH N H HO HO 4 + 7 'OH N Ox- ^ HO 64 Scheme 1: Conditions a) PPh3, CCI4 (added over 3 h), EtsN, CH2CI2, rt 36 ri t>J Pd/C: H2, MeQH rt 12 h c) CH^CI2: rt, 1 ri d) Pivalloyl chloride, toluene, Et3N, rt, 13 h |