Undergraduate Research Opportunities Undergraduate Research Opportunities Program (UROP) Program (UROP) 2010 Aug 3rd, 9:00 AM - 12:00 PM Synthesis of Bis-styrylbenzene derivatives via Wittig-Horner reaction Joseph K. Wray University of Nevada, Las Vegas Tae Soo Jo University of Nevada, Las Vegas Pradip K. Browmik University of Nevada, Las Vegas Follow this and additional works at: https://digitalscholarship.unlv.edu/cs_urop Part of the Medicinal-Pharmaceutical Chemistry Commons, and the Organic Chemistry Commons Repository Citation Wray, Joseph K.; Jo, Tae Soo; and Browmik, Pradip K., "Synthesis of Bis-styrylbenzene derivatives via Wittig-Horner reaction" (2010). Undergraduate Research Opportunities Program (UROP). 33. https://digitalscholarship.unlv.edu/cs_urop/2010/aug3/33 This Event is protected by copyright and/or related rights. It has been brought to you by Digital Scholarship@UNLV with permission from the rights-holder(s). 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Bhowmik* Department of Chemistry, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154 • Alzheimer’s Disease is now one of the most common diseases R1 CHO • Reflux under N conditions to carry out reactions affecting the elderly population 2 Base, Solvent • Distillation under pressure to remove solvents Heat • Recently, bis-styrylbenzene derivatives have been shown to OH • Extraction via ether to separate organic and aqueous layers reduce the formation of Beta-amyloid plaques in the brain which PO(OEt)2 PO(OEt)2 OCH3 • Dried with Na SO H3CO OCH3 are profoundly correlated with this disease 2 4 OH OH • Column filtration was used to separate products • Finding new biologically active compounds which can reduce or • 1H NMR and Thin Layer Chromatography used to identify Entr Base Solvent Time Temp Comment prevent Alzheimer’s Disease has drawn much attention over the product past few decades y ` s • Georg Wittig, Nobel Prize Winner in Chemistry, 1979 1 NaOH DMF 6 h Reflux No rxn 2 NaOH DMF 12 h Reflux No rxn Organic 3 KOH DMF+EtOH 12 h Reflux No rxn • To attempt to synthesize a new bis-styrylbenzene derivative, Aqueous 4 KOH THF 12 h R. T. Mono-Anion (trans,trans)-1,3-bis-3´-hydoxy-4´-methoxystyrylbenzene, via the Product Wittig-Horner reaction tailored to select for the trans-alkene 5 KOH THF 12 h Reflux Mono-Anion product Product • Synthesize the phosphonate ylide 6 NaH DMF 12 h 100 oC Mono-Anion O O Product O P O O P O • React the ylide with an aldehyde to create a bis-styrylbenzene • The phosphonate molecule was successfully synthesized with a TLC • The trans-alkene product has been shown to be effective in H consistent yield (77%) and its molecular structure was confirmed C H H 1 C reducing Beta-amyloid plaques C by H NMR spectroscopy C C • The hydroxyl and methoxy R groups render this derivative less H • To generate the phosphonate ylide, different types of bases were C C H C H H H C cytotoxic C C used for the Wittig-Horner reaction C H H H H C C C • Closest known relative is (trans,trans)-1,3-bis-3´-methoxy-4´- C • The formation of the di-anion product was unsuccessful, instead C C C C H C O H hydroxystyrylbenzene O C the mono-anion product was created Anion Anion O H C - O H H H • Mono-anion phosphonate ylide produces an undesirable product H C H H H Product • Future direction would lead to the exploration of a suitable 4. Mono 4. 3. Crude Product Crude 3. 2. Aldehyde 2. 1. Phosphonate 1. HO OH base/solvent system that would create a di-anion suspension before the aldehyde was added H3CO OCH3 1. Nicholas, B.; Sandman, D.J.; Tripathy, S.; Kumar, J.; Yang, K.; Rubner, M. F.; Lyons, R 1 R1 C. Macromolecules 1998. 31, 3595-3599. 2x P(OCH2CH3)3 2. Seong B.; Lee, J. H.; Sohn, J. H.; Kim, D. C.; Shin, K. J.; Yoo, K. H.; Jung, I.-M.; Lee, DMSO W. K.; Kim, D. J. Bioorganic & Med. Chem. Letters 2007. 17, 466-470. Br Br PO(OEt)2 PO(OEt)2 3. Justin, J. H.; Weber, W. M.; Juunsaker, L. A.; Gonzales, A. M.; Orlando, R. A.; Deck, L. M.; Vander Jagt, D. L. J. Med. Chem. 2006. 49, 7182-7189. CHO 4. Wen, X.; Lan, T.; Xiang, Y.-Z.; Fang, Y.-G.; Yu, X.-Q. ARKIVO XIII 2005. 169-174 a) NaOH, EtOH, DMF, 18-Crown-6 a), b), c) or d) 2x b) KOH,EtOH, DMF, 18-Crown-6 c) KOH, THF R2 d) NaH, anhydrous DMF R3 R1 I am very grateful for the cooperation and interest of the professors and R1 = H or Cl students who took part in this phase of my research. It would not have been R = -OH 2 possible without their help. This poster was made possible by NIH Grant R3 = -OCH3 R3 R3 Number P20 RR-016464 from the INBRE Program of the National Center for R2 R2 Research Resources..