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

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Part of the Medicinal-Pharmaceutical 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

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This Event has been accepted for inclusion in Undergraduate Research Opportunities Program (UROP) by an authorized administrator of Digital Scholarship@UNLV. For more information, please contact [email protected]. Joseph K. Wray, Tae Soo Jo, and Pradip K. 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, 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- 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 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.