Christopher D. Spilling
Dr.
Spilling received his B.Sc. (Hons.) degree and Ph.D. degree from
the University of Technology, Loughborough, England. He was a
Postdoctoral Fellow at Northwestern University before joining
the UM-St. Louis faculty in 1989.
cspill@umsl.edu
Office: B315
Phone: (314) 516-5437
Fax: (314) 516-5342
The last decade has seen a rapid expansion in the interest in the asymmetric synthesis of 1-substituted phosphonates. The unique properties of phosphorus provide a fascinating and challenging approach to stereoselective reactions. Our goal is to examine the use of chiral phosphonamides and phosphonates in stereoselective reactions. We reported the first example of a lathanide chiral catalyst in the addition of simple phosphites to achiral aldehydes. More recently, we discovered some promising titanium alkoxide systems. We are attempting to expand the chemistry of allylic hydroxy phosphonamides and phosphonates formed in the chemistry discussed above. Allylic hydroxy phosphonates are similar to regular allylic alcohols and should undergo similar chemistry. However, the presence of the phosphonate significantly alters the electronics of the system, and enables control of both regiochemistry and stereochemistry. Our initial work focused on the palladium catalyzed addition of amines to the carbonate derivatives of allylic hydroxy phosphonates, and several examples of this reaction have been performed. The rearrangement proceeds with complete retention of chirality. A number of 3,3 sigmatropic rearrangements and alkene addition reactions have been studied. The newly developed chemistry of the hydroxy phosphonates is being applied toward the synthesis of the cathepsin B, cruzain, and renin inhibitors, lactones and lactams.
Psammapsylin, fistularin, and the bastadins are related metabolites isolated from sponges found worldwide. This family of highly brominated compounds possess wide ranging biological activity, including anti-HIV activity, and anti-tumor properties. They are related in their biosynthetic origin, as oxidation products of tyrosine. We are exploring biomimetic approaches to the synthesis of several of these metabolites. The development of new methodology is guided by the biosynthetic pathway proposed for the formation of the tyrosine metabolites. As an extension of this project, we recently initiated research into methods for the facile synthesis of unsymmetric biaryl ethers.
Selected Publications
"Asymmetric Synthesis of 2-Alkyl-3-phosphonopropanoic Acids via P-C Bond Formation and Hydrogenation", P. A. Badkar, N. P. Rath and C. D. Spilling, Org. Lett. 2007, 9, 3619.
"Total synthesis of rapamycin", M. L. Maddess, M. N. Tackett, H. Watanabe, P. E. Brennan, C. D. Spilling, J. S. D. P. Osborn and S. V. Ley, Angew. Chem. Int. Ed. 2007, 46, 591.
"Efficient Synthesis of Tyrosine-Derived Marine Sponge Metabolites via Acylation of Amines with a Coumarin", J. Harburn and C. D. Spilling, J. Org. Chem. 2005, 70, 6398.
"Effect of Ligand Structure on the Pathways for Iron Release from Human Serum Transferrin", C. E. Brook, W. R. Harris, C. D. Spilling, P. Wang, J. Harburn and S. Srisung, Inorg. Chem. 2005, 44, 5183.
“Allylic hydroxy phosphonates: versatile chiral building blocks", A. De la Cruz, A. He, A. Thanavaro, B. Yan, C. D. Spilling and N. P. Rath, J. Organomet. Chem. 2005, 690, 2577.
"Release
of Iron from Transferrin by Phosphonocarboxylate and Diphosphonate
Chelating Agents", W. R. Harris, C. E. Brook, C.
D. Spilling, S. Elleppan, W. Peng, M. Xin, and J.
Van Wyk, Journal of Inorganic Biochemistry, 2004, 98,
1824-.
“The Synthesis of Non-Racemic Allylic Hydroxy Phosphonates via
Alkene Cross Metathesis", C. D. Spilling, A. He, B.i
Yan and A. Thanavaro Journal of Organic Chemistry, 2004, 69,
8643.
“Stereospecific Pd(0)-Catalyzed Malonate Additionss to Allylic Hydroxy
Phosphonate Derivatives: A Formal Synthesis of (-) Enterolactone”, B.
Yan and C. D. Spilling, Journal of Organic Chemistry, 2004, 69,
2859.
“Stereospecific Pd(0)-Catalyzed Arylation of an Allylic Hydroxy Phosphonate
Derivative: Formal Synthesis of Turmerone”, B. J. Rowe and C.
D. Spilling, Journal of Organic Chemistry, 2003, 68,
9502.
“Effects of Proline Analogue Binding on the Spectroscopic and Redox Properties
of PutA”, W, Zhu, Y, Gincherman, P, Docherty, C,r
D. Spilling and D. F. Becker, Archives of Biochemistry and Biophysics, 2002, 408,
131.
"Palladium
Catalyzed Additions to Allylic Hydroxy Phosphonates: Applications
in the Enatioselective Synthesis of Enterolactone and Turmerone", B.
J. Rowe, J. Scholten, and C. D. Spilling, Phosphorus,
Sulfur and Silicon, 2002, 177, 1881.
"The Synthesis of 1-Hydroxy Phosphonates of High Enantiomeric Excess
using Sequential Asymmetric Reactions: Titanium Alkoxide Catalyzed
P-C Bond Formation and Kinetic Resolution", B. J. Rowe and C. D. Spilling, Tetrahedron
Assymmetry, 2001, 12, 1701.
Approaches to the Synthesis of Some Tyrosine Derived Sponge Metabolites: Synthesis
of Verongamine and Purealidin N", T. R. Boehlow, J. J. Harburn, and C. D. Spilling, Journal
of Organic Chemistry, 2001, 66, 3111.
"Chemistry of Insect Antifeedants from Azadirachta indica (Part 22): Functionalization
of the Decalin Fragment of Azadirachtin via a Claisen Rearrangement reaction", S.
V. Ley, C. E. Gutteridge, A. R. Pape, C. D. Spilling, and Cornelia Zumbrunn Synlett, 1999,
1295