Martin Di Grandi
Associate Professor of Chemistry
Offices: Lincoln Center 808C | Rose Hill JMH 538
Lincoln Center: 212-636-7141 | Rose Hill: 718-817-4447
Ph.D., March 1990, New York University
B.Sc., May 1984, Fordham University
- Thioureas as Inhibitors of Herpesviruses. Herpesviridae is a family of double stranded DNA viruses, of which there are eight that afflict humans, and all are characterized by intermittent periods of infection followed by latency. Each member of this viral family employs the portal protein, an essential viral protein, for the packaging and release of viral DNA during infection. More importantly, these proteins possess remarkable structural and functional relatedness across all known members of this virus family. The focus of this research is to potentially identify one agent that can effectively inhibit the viral replication of multiple herpesviruses. If true, this agent would not only add to the repertoire of agents for treating herpesvirus infections but given its very different mechanism of action – the lead structures are not nucleosides and will inhibit viral replication by a different means relative to available treatments – these compounds are likely to be equally effective against resistant virus.
- 1,2,3,4-Tetrahydroisoquinoline Synthesis. This project, at its core, involves the ring expansion of activated N-benzylaziridines to 1,2,3,4-tetrahydroiso-quinolines (see below). More broadly, we hope to incorporate this chemistry into the synthesis of the tricyclic core ring system of the natural product pancratistatin, an anticancer agent that has been in clinical trials. Ultimately, depending on the final optimized conditions, we anticipate this methodology to be amenable to the total synthesis of the natural product.
- Probing the Diastereoselective Reduction of α-hydroxyketones with Sodium Borohydride. An experiment conducted in second semester Organic Chemistry lab is the reduction of racemic benzoin with NaBH4, which is known to be highly diastereoselective, yielding only one of two possible diastereomeric diols. This project has yielded alternative conditions that allows for the preparation of the other diastereomeric diol. Once this can be appropriately reduced to practice for students, the plan is to have half the class conduct the reduction under “traditional” conditions and the other half to employ the new method. Then, both groups will use NMR spectroscopy to determine the stereochemistry of each reduction product.
Di Grandi, M.; Berger, D. M.; Hopper, D. W.; Zhang, C.; Dutia, M.; Dunnick, A. L.; Torres, N.; Levin, J. I.; Diamantidis; G.; Zapf, C. W.; Bloom, J. D.; Hu, Y.; Powell, D.; Wojciechowicz; D.; Collins, K.; Frommer, E. “Novel Pyrazolopyrimidines as Highly Potent B-Raf Inhibitors”, Bioorg. Med. Chem. Lett., 2009, 19(24), 6957-6961.
Di Grandi, M.; Olson, M.; Prashad, A. S.; Bebernitz, G.; Luckay, A.; Mullen, S.; Hu, Y.; Krishna- murthy, G.; Pitts, K.; O’Connell, J. “Small Molecule Inhibitors of HIV RT Ribonuclease H”, Bioorg. Med. Chem. Lett., 2010, 20(1), 398-402.
Di Grandi, Martin J. “Nazarov-like Cyclization Reactions”, Org. Biomol. Chem., 2014, 12(29), 5331- 5345.
Di Grandi, M. J., Bennett, C.; Cagino, K.; Muccini, A.; Suraci, C.; Saba, S. “The Direct Preparation of Amides from Amine Hydrochloride Salts and Orthoesters: A Synthetic and Mechanistic Perspective”, Syn. Comm., 2015, 45(22), 2601-2607.
Di Grandi, M. J., Taylor, B., Corfield, P. W. R. “The crystal structure of 2-[(tert-butyldiphenylsilyl)oxy]-1,2-diphenylethan-1-one”, International Union of Crystallography Data (IUCr), 2019, 4; (https://doi.org/10.1107/S2414314619004784).
Olson, M. W.; Di Grandi, M.; Prashad, A. “Preparation Of Hydantoins Having RNASE Modulatory Activity.” U.S. Pat. Appl. Publ.2005; 16 PP.; US 2005203156 A1.
Olson, M. W.; Di Grandi, M.; Prashad, A. “Carbamates as HIV Anti-Viral Agents.” U.S. Pat. Appl. Publ. 2005, 15 PP.; US 2005203176 A1.
Hu, Y.; Sum, F.-W.; Di Grandi, M.; Norton, E. “Preparation Of Anilino-Pyrimidine Phenyl And Benzothiophene Analogs As Protein Kinase Inhibitors For Treating Inflammatory, Autoimmune, Cardiovascular And Other Disease.” U.S. Pat. Appl. Publ. 2007, 36 PP; US 2007244140 A1.
Olson, M.; Di Grandi, M.; Prashad, A. “Preparation Of 1,2-Dihydroquinoline Derivatives As Inhibitors Of RNASE H And HIV Reverse Transcriptase.” 2009, US Patent 7,553,967, June 30, 2009.
Olson; M.; Di Grandi, M. “Preparation Of Triazole Derivatives For Treating HIV Infections.” 2009, US Patent 7,563,905, July 21, 2009.
Levin, J. I.; Hopper, D. W.; Torres, N.; Dutia, M. D.; Berger, D. M.; Wang, X.; Di Grandi, M. J.; Zhang, C.; Dunnick,A.L. “Preparation Of Bridged, Bicyclic Heterocyclic Or Spiro Bicyclic Heterocyclic Derivatives Of Pyrazolo[1,5-A]Pyrimidines as RAF Kinase Inhibitors”, Pct Int. Appl., 2009, 159 PP; WO 2009108838 A1.