Orange Alert

Skip to main content
Syracuse University, College of Arts and Sciences

John D. Chisholm

John Chisholm portrait




4-006 Center for Science and Technology


Research Interests

organic chemistry, medicinal chemistry, synthesis, catalysis, organometallic chemistry


  • B.S., 1992, Alma College
  • Ph.D., 2000, University of California, Irvine
  • Postdoctoral Fellow, 2000-2002, Stanford University

Honors & Awards

  • Editorial Board, Scientific Reports, 2016-present
  • Scientific Advisory Board, Alterna Therapeutics, 2016-present
  • Nappi Family Research Award, 2015-2016
  • NIH Academic Research Enhancement Award, 2015-2018
  • National Institute of Health Postdoctoral Fellowship, 2000-2002
  • Bristol-Myers Squibb Graduate Fellowship, 1999-2000


  • CHE 275: Organic Chemistry
  • CHE 575: Organic Spectroscopy
  • CHE 675: Advanced Organic Chemistry
  • CHE 676: Introduction to Organic Synthesis: Methodology
  • CHE 686: Introduction to Organic Synthesis: Design

Research Focus

Research in the Chisholm group is focused on organic chemistry, broadly defined. This includes studies in medicinal chemistry, catalysis and natural products synthesis. Current projects include:

  1. Medicinal chemistry on small molecule modulators of the inositol phosphatase SHIP
  2. The exploration of new synthetic methods
  3. The synthesis of complex natural products

Medicinal Chemistry

In collaboration with the Kerr laboratory at SUNY Upstate Medical University, we have been developing new inhibitors of the SH2-containing Inositol 5’-Phosphatase SHIP. SHIP is a phosphatase that selectively removes a phosphate from the 5’ position of the inositol substrate PI(3,4,5)P3. The phosphorylation pattern on these inositols act as control elements in passing signals from the outside of the cell membrane to the nucleus of the cell, which is turn influence migration, growth and survival (Figure 1). By influencing the activity of the phosphatase SHIP a number of these important cellular events can be regulated. This regulation may be beneficial for a number of disease states, including cancer, diabetes, and anemia. Therefore small molecule inhibitors of SHIP are of great interest.

graphic showing cell membrane with receptor and chemical attachments.
Figure 1. The role of SHIP in cellular signaling

A number of small molecule inhibitors of SHIP have been found by high throughput screening (Figure 2A). Medicinal chemistry studies have now commenced on these structures to improve the potency and pharmacodynamic properties of these molecules so that they may be used to probe the role of SHIP in a number of in vitro and in vivo model systems. Currently a number of approaches are being used to facilitate these studies, including complex molecule synthesis and in silico docking studies on the active site of the enzyme (Figure 2B).

Graphic of small molecule SHIP inhibitor
Figure 2. A) The structures of small molecule inhibitors of SHIP found through high throughput screening.
graphic of green ribbon and string representing the crystal structure of an active site
Figure 2. A) The structures of small molecule inhibitors of SHIP found through high throughput screening.

Development of New Synthetic Methods

Recent investigations into the reactivity of trichloroacetimidates have also been fruitful (Figure 3). Trichloroacetimidates are known to be excellent alkylating agents when activated by a catalytic amount of a Brønsted acid. Some preliminary forays into this area showed that many imidates are much more reactive than predicted by early studies, with carboxylic acids, alcohols and thiols being alkylated by the imidates without the need for a catalyst. In addition, other nucleophiles like anilines and sulfonamides have been shown to be competent nucleophiles in the presence of an acid catalyst. The alkylation of carboxylic acids and alcohols appears to be limited to more reactive imidates, but is still useful in the installation of PMB and DPM protecting groups. The alkylation of anilines and thiols has a wider substrate scope. Preliminary studies have shown that these new trichloroacetimidate substitution reactions are less prone to competing elimination than methods using sulfonate-leaving groups. Additionally, these imidate substitution reactions may be amenable to asymmetric catalysis.

graphic in black and white showing a crystal with possible substitution pathways
Figure 3. New substitution reactions with trichloroacetimidates

Complex Molecule Total Synthesis

We are also interested in developing new synthetic routes to complex molecules with interesting biological activity. Some targets that are currently of interest are shown below (Figure 4). These studies provide material to explore the biological properties of these molecules. Many of these molecules are natural products, which have long been a primary source of therapeutic agents and candidate molecules.

five different crystal structures
Figure 4. Natural product targets

Selected Publications

Mahajani, N. S.; Meador, R. I. L.; Smith, T. J.; Canarelli, S. E.; Adhikari, A. A.; Shah, J. P.; Russo, C. M.; Wallach, D. R.; Howard, K. T.; Millimaci, A. M.; Chisholm, J. D. “Ester Formation via Symbiotic Activation Utilizing Trichloroacetimidate Electrophiles” J. Org. Chem. 2019, 84, 7871-7882. DOI:10.1021/acs.joc.9b00745

Friedel-Crafts Alkylation of Indoles with Trichloroacetimidates.

Suzuki, T.; Chisholm, J. D. "Friedel-Crafts Alkylation of Indoles with Trichloroacetimidates." Tetrahedron Lett., 2019, 60, 1325-1329. DOI:10.1016/j.tetlet.2019.04.007

The Next Generation of Immunotherapy for Cancer: Small Molecules Could Make Big Waves.

Kerr W. G.; Chisholm, J. D. “The Next Generation of Immunotherapy for Cancer: Small Molecules Could         Make   Big Waves.” J. Immunol. 2019, 202, 11-19. DOI:10.4049/jimmunol.1800991

Ruthenium Dihydride Complexes as Enyne Metathesis Catalysts.

Dolan, M. A.; Dixon, A. D. C.; Chisholm, J. D.; Clark, D. A. “Ruthenium Dihydride Complexes as Enyne Metathesis Catalysts.” Tetrahedron Lett. 2018, 59, 4471-4474. DOI:10.1016/j.tetlet.2018.11.016

Targeting SHIP-1 in Myeloid Cells Enhances Trained Immunity and Boosts Response to Infection.

Saz-Leal, P.; del Fresno, C.; Brandi, P.; Martínez-Cano, S.; Dungan, O. M.; Chisholm, J. D.; Kerr, W. G.; Sancho, D. “Targeting SHIP-1 in Myeloid Cells Enhances Trained Immunity and Boosts Response to Infection.” Cell Rep. 2018, 23, 1118-1126. DOI:10.1016/j.celrep.2018.09.092

A multisubstrate reductase from Plantago major: structure-function in the short chain reductase superfamily.

Fellows, R.; Russo, C. M.; Silva, C. S.; Lee, S. G.; Jez, J.; Chisholm, J. D.; Zubieta, C.; Nanao, M. "A multisubstrate reductase from Plantago major: structure-function in the short chain reductase superfamily." Sci. Rep. 2018, 8, 14796. DOI:10.1038/s41598-018-32967-1

Promoter free allylation of trichloroacetimidates with allyltributylstannanes under thermal conditions to access the common 1,1′-diarylbutyl pharmacophore

Mahajani, N. S.; Chisholm, J. D. " Catalyst Free Allylation of Trichloroacetimidates with Allyltributylstannane Under Thermal Conditions to Access the Common 1,1’-Diarylbutyl Pharmacophore." Org. Biomol. Chem. 2018, 16, 4008-4012. DOI:10.1039/C8OB00687c

  • Mahajani, N. S.; Chisholm, J. D. " Synthesis of 1,1’-Diarylethanes and Related Systems by Displacement of Trichloroacetimidates with Trimethylaluminum." J. Org. Chem. 2018, 83, 4131-4139. DOI:10.1021/acs.joc.8b00027
  • Wilhelmsen, C. A.; Dixon, A. D. C.; Chisholm, J. D.; Clark, D. A. “Synthesis of N-Substituted-3-amino-4-halopyridines: a Sequential Boc-Removal/Reductive Amination Mediated by Brønsted and Lewis Acids.” J. Org. Chem. 2018, 83, 1634-1642. DOI:10.1021/acs.joc.7b02966
  • Dushukyan, N.; Dunn, D. M.; Sager, R. A.; Woodford, M. R.; Loiselle, D. R.; Daneshvar, M.; Baker-Williams, A. J.; Chisholm, J. D.; Truman, A. W.; Vaughan, C. K.; Haystead, T. A.; Bratslavsky, G.; Bourboulia, D.; Mollapour, M. “Phosphorylation and Ubiquitination Regulate Protein Phosphatase 5 Activity and Its Prosurvival Role in Kidney Cancer.” Cell Reports 2017, 21, 1883-1895. DOI:10.1016/j.celrep.2017.10.074
  • Gumbleton, M.; Sudan, R.; Fernandes, S.; Engelman, R. W.; Russo, C. M.; Chisholm, J. D.; Kerr, W. G. "Dual enhancement of T and NK cell function by pulsatile inhibition of SHIP1 improves antitumor immunity and survival." Sci. Signal. 2017, 10, eaam5353. DOI:10.1126/scisignal.aam5353
  • Adhikari, A. A.; Radal, L.; Chisholm, J. D. "Synthesis of 3,3′-Disubstituted Indolenines Utilizing the Lewis Acid Catalyzed Alkylation of 2,3-Disubstituted Indoles with Trichloroacetimidates." Synlett 2017, 28, 2335-2339. DOI:10.1055/s-0036-1588491

Complete list of publications available on NCBI MyBibliography


Chemistry department awarded over $700,000 to support graduate diversity

(Oct. 11, 2016)

United States Department of Education grant will support at least four students

Syracuse Chemists Awarded Grants for Interdisciplinary Research

(Sept. 4, 2015)

Professors Yan-Yeung Luk, John Chisholm redefine possibilities of organic chemistry