Dr. Micheal Fultz

EDUCATION

B.S., University of Tennessee, Martin

Ph.D., Chemistry, Indiana University

 

Research Interests

Total synthesis of Natural Products

Nature has been making complex molecules since life began.  These molecules were designed for a particular purpose, to protect from attack, to act as a chemical signal, assist in digestion, or countless other biological functions.  These molecules are found around the world from the ocean bottom to the highest mountain peak. These molecules were designed to be biological active that is they do something in a cell whether it is advantageous for the cell or detrimental.  Mankind has begun to study these molecules for their activity against diseases, bacteria, and viruses.

Today with billions of dollars being spent on drug discovery and design much attention has been spent on examining these molecules for their biological activity.  Currently approximately 70% of the pharmaceutical drugs on the market are natural products or some derivative of a natural product.

 

[i]

  From asprin to taxol these molecules make our lives better.  In the fight against these microbes develop resistance to our current arsenal of drugs and cleaners so we must develop a stronger a more diverse structural database to employ against the problem microbes that can devastate our health and wreak havoc on our economy.  Currently we are working on two separate molecules that display significant biological activity.

 

Spathoside.

Spathoside, a biologically active metabolite was isolated from the stem bark of the African tulip tree.[ii]

 

  The structure was proven to be 1 through a combination of spectroscopic techniques, however, the absolute and relative stereochemistry of the three chiral centers marked with an asterisk in 1 has not been determined. Natural spathoside shows a broad diversity of biological activity, showing potential activity against gram positive (3.12 µg per mL minimum inhibitory concentration) and negative bacteria (3.2 µg per mL minimum inhibitory concentration).  On the basis of this outstanding biological activity and our desire to understand the origin of this activity, we are set to undertake an extensive investigation into the synthesis of spathoside and a number of derivatives.   

There are no total syntheses of spathoside to date.  Any potential medicinal chemistry applications utilizing this molecule or any derivative would require an efficient synthesis.  This synthesis will be completed by coupling framnets 2 – 4 to form all 8 stereotriads possible of 1. My research will approach this problem in two different ways. The first is to design an efficient synthesis, amenable to large-scale preparation. The second and perhaps more important goal is to try determine what the stereochemistry of each of the three unknown centers are (1 center in 3 and 2 in 4).

 

Dihydroresveratrol dimers

Resvaratrol (5), a biologically active metabolite, has been  isolated from from several plants most notably the Eucalyptus Tree.[iii]

 

Since the discovery of resveratrol it has been used in numerous studies ranging from potassium channel modulators,[iv]

 

anti-allergic activity,[v]

 

to examining the antileukemic properties.[vi]

 

Derivatives of Resveratrol have an extensive history of being studied for biological activity.  Xie and coworkers have a promising study. Coupling dihydroresveratrol through enzamatic catalysis they obtained a variety of dimers that showed more potent activity against prostate cancer than the parent compound.[vii]

 

 

To date, there are no selective controlled total syntheses of the dihydroresveratrol derivatives 6-11.  Any potential medicinal chemistry applications utilizing this molecule would require an efficient synthesis.  The goal of the project is to design an efficient synthesis, amenable to large-scale preparation of each of the biologically active molecules.
 

Publications

Williams, D. R.; Fultz, M.W.  Christos, T. E.; Carter, J. S. A general preparation of (Z)-1-fluorostilbene derivatives for the design of conformationally restricted peptidomimetics. Tet. Lett. 2009, 51, 121-124.

Fultz, M. W. Progress toward the total synthesis of Amphidinolide C. Ph. D. Thesis, Indiana University, July 2009.

 

Williams, D. R.; Fultz, M. W. N,N-Dimethylacetamide Dimethyl Acetal, Electronic Encyclopedia of Reagents for Organic Synthesis, Molander, G., Ed.; John Wiley & Sons Ltd.:  Sussex, 2008, in press.

 

Williams, D. R.; Fultz, M.W.  1-Alkoxyallene as an Effective Precursor for Regio- and Stereocontrolled Allylation Reactions with Aliphatic Aldehydes via Bis-Stannylation.  J. Am. Chem. Soc.  2005, 127, 14550-14551.

 

Airee, S. K.; Fultz, M. W. UT-Martin Students Affiliate with Green Chemistry. In Chemistry. 2002, 3, 18-19

 

Presentations

“Community outreach to disadvataged schools and building a successful chapter in a single academic year,” Fultz, Micheal W.; Mundy, Lindsey; Workman, Rachael; 241st ACS National Meeting, Anaheim, CA, 2011; CHED-1316.  

“Progress toward the total synthesis of spathoside,” Nogoda, Nicolas W.; Ratcliff, Brittany M.; Fultz, Micheal W.; 241st ACS National Meeting, Anaheim, CA, 2011; CHED-1030.

Progress towards the synthesis of dihydroresveratrol dimers,” Morris, Robert J.; Fultz, Micheal W.;   241st ACS National Meeting, Anaheim, CA, 2011; CHED-909.

“Studies toward the total synthesis of amphidinolide C,” Fultz, Micheal; De, Ramkrishna; McCoy, Michael; Morales-Ramos, Angel I.; Williams, David R.; 237th ACS National Meeting Salt Lake City, Utah, March 28, 2009; ORGN-524.

  

“Green chemistry and NCW give UTM SAACS outreach focus,” Kirkpatrick, Rebekah; Fultz, Micheal Wayne; Airee, S. K.; Chris, Schmitt; Reeves, Emili L.; 225th ACS National Meeting, New Orleans, LA, March 25, 2003;    CHED-1110. 

 

“Synthesis of silicon-based platforms for heterogeneous catalysis,” Fultz, Micheal Wayne, Barnes, C. E.    225th ACS National Meeting, New Orleans, LA, March 25, 2003; CHED-726

 

“A focus on the role of hydrogen peroxide in green chemistry,” Parnell, Selena M.; Myers, Clint E.; Airee, S. K.; Fultz, Micheal Wayne, 223rd ACS National Meeting, Orlando, FL, April 10, 2002; CHED-987. 

 

“Preparation of new Fremy's salt derivatives to improve thermal stability,” Fultz, Micheal Wayne; Blackstock, Silas, 223rd ACS National Meeting, Orlando, FL, April 10, 2002; CHED-768. 

 

Lab Members

 

Undergraduate Students:

Robert Morris

William Rollyson

[i]

 

Chin, Y-W.; Balunas, M. J.; Chai, H. B.; Kinghorn, A. D.; Drug Discovery from natural Sources The AAPS Journal vol 8, pp239, 2006.

[ii].  Mbosso, E. J. T.; Ngouela, S.; Nguedia, J. C. A.; Bengs, V.P.; Rohmer, M.; Tsamo, E. Spathoside, a cerebroside and other antibacterial constituents of the stem bark of Spathodea campanulata Nat. Prod. Res. Vol 22, pp296, 2008.

[iii] Hathway, D. E.; Seakins, J. W. T. The occurrence of hydroxystilbenes in Eucalyptus Biochemical Journal vol. 72, pp 37, 1959.

[iv] Ito, T.; Abe, N.; Ali, Z.; Oyama, M.; Tanaka, T.; Sawa, R.; Takahashi, Y.; Murata, J.; Darnaedi, D.; Iinuma, M. Two New Resveratrol Tetramers from Upuna Borneensis Chemistry & Pharmaceutical Bulletin vol. 57, pp 516, 2009.

[v] Matsuda, H.; Tewtrakul, S.; Morikawa, T.; Yoshikawa, M., Antiallergic activity of stillbenes from Korean Rhubarb (Rheum undulatum L.): structure requirements for inhibition of antigen-induced degranulation and their effects on the release of TNF-a and IL-4 in RBL-2H3 cells Bioorganic & Medicinal Chemistry vol. 12, pp 4871, 2004.

[vi] Mannila, E.; Talvitie, A.; Kolehmainen, E. Antileukemic compounds derived from stilbenes in Picea abies bark Phytochemistry vol. 32, pp 1561, 1993.

[vii] Xie, C. F.; Yuan, H. Q.; Qu, J. B. Xing, J. Lu, B. B.; Wang, X. N. Ji, M.; Lou, H. X. Biocatalytic Production of Acyclic Bis[bibenzyls] from Dihydroresveratrol by Crude Momordica charantia Peroxidase Chemistry and Biodiversity vol 6, pp 1193, 2009.