Robert B. Grossman

Education:
A.B. in Chemistry, Princeton University, 1987
Ph.D. in Organic Chemistry, Massachusetts Institute of Technology, 1992
Research Interests:
Synthetic Organic Chemistry
Biosynthesis
Education

A.B., Princeton University, 1987
Ph.D., Massachusetts Institute of Technology, 1992

Research

Our group develops new synthetic methods and applies them to the synthesis of natural products and biologically relevant compounds. Students learn skills that prepare them for employment in the pharmaceutical and contract synthesis industries.

We have developed two new methods for the 1,2-diamination of alkenes. We are also exploring new total synthetic routes to loline using one of these methods.

1,2-diamination methods

 

New Pedagogy

As a service to the research community, I have created an online database of all of the polycyclic polyprenylated acylphloroglucinols (PPAPs) discovered to date.

I am the author of The Art of Writing Reasonable Organic Reaction Mechanisms, an intermediate-level textbook for advanced undergraduates and beginning graduate students. 

I am also a creator of ACE Organic, a Web-based program for organic chemistry homework that guides students to the correct answer without giving away the answer. 

Selected Publications:

Research papers from independent career:

  1. Juan Pan, Eliott S. Wenger, Chi-Yun Lin, Bo Zhang, Debangsu Sil, Irene Schaperdoth, Setareh Saryazdi, Robert B. Grossman, Carsten Krebs, and J. Martin Bollinger, Jr. "An Unusual Ferryl Intermediate and its Implications for the Mechanism of Oxacyclization by the Loline-Producing Iron(II)- and 2-Oxoglutarate-Dependent Oxygenase, LolO." ChemRxiv 2024. 
  2. Yu-Feng Qiu, Robert B. Grossman, and Xing-Wei Yang. "Structure Revision of Type B Polycyclic Polyprenylated Acylphloroglucinols Fused to a Partly Reduced Furan Ring." J. Nat. Prod. 2023, 86 (10), 2391.
  3. Sailajah Gukathasan, Oluwatosin Obisesan, Setareh Saryazdi, Libby Ratliff, Sean Parkin, Robert B. Grossman, and Samuel Awuah. "A Conformationally Restricted Gold(III) Complex Elicits Antiproliferative Activity in Cancer Cells." Inorg. Chem. 2023, 62 (32), 13118.
  4. Yang Luo, Robert B. Grossman, Xiao-Bin Nie, and Xing-Wei Yang. "Total synthesis and structural reassignment of garcinielliptone FC, a polycyclic polyprenylated acylphloroglucinol with diverse bioactivity." Chem. Commun. 2023, 59 (41), 6215.
  5. Setareh Saryazdi, Sean Parkin, and Robert B. Grossman. "1,2-Diamination of alkenes via 1,3-dipolar cycloaddition with azidium ions or azides." Org. Lett. 2023, 25 (2), 331.
  6. Zhi-Hong Xu, Robert B. Grossman, Yu-Feng Qiu, Yang Luo, Tian Lan, and Xing-Wei Yang. "Structural Determinations of Polycyclic Polyprenylated Acylphloroglucinols Bearing a Lavandulyl-derived Substituent from Garcinia xanthochymus Fruits." J. Nat. Prod. 2022, 85 (12), 2845.
  7. Nabin Panth, Eliott S. Wenger, Carsten Krebs, J. Martin Bollinger, Jr., and Robert B. Grossman. "Synthesis of 6,6- and 7,7-difluoro-1-acetamidopyrrolizidines and their oxidation catalyzed by the nonheme Fe oxygenase LolO." ChemBioChem 2022, 23 (13), e202200081.
  8. Jingbo Sun, Zhonglin Wei, Robert B. Grossman, and Ran Lu. "ACE: Organics Chemistry Homework Program that Offers Intelligent Feedback to Students and its Application in College Teaching." Chin. J. Chem. Educ. 2022, 43 (8), 106.
  9. Xiaohui Wang, Xiao-Bin Nie, Robert B. Grossman, Tengfei Ji, and Xing-Wei Yang. "Structural Reassignments of Hyperibrin B and Hyperscabrones H and I by Biosynthetic Considerations, NMR, and Chemical Synthesis." J. Nat. Prod. 2021, 84 (7), 2059–2064.
  10. Robert B. Grossman and Xing-Wei Yang. "Structural revision of garcinielliptin oxide and garcinielliptone E." J. Nat. Prod. 2020, 83 (6), 2041–2044.
  11. Xing-Wei Yang and Robert B. Grossman. "Revision of the Structure of Hypatulone A by NMR, Computations, and Biosynthetic Considerations." Org. Lett. 2020, 22 (2), 760–763.
  12. Minakshi Bhardwaj, Qianxiang Ai, Sean R. Parkin, and Robert B. Grossman. "An unusually short intermolecular N—H···N hydrogen bond in crystals of the hemi-hydrochloride salt of 1-exo-acetamidopyrrolizidine." Acta Cryst. 2020, E76 (1), 77–81.
  13. Juan Pan, Eliott Wenger, Megan Matthews, Christopher Pollock, Minakshi Bhardwaj, Amelia Kim, Benjamin Allen, Robert B. Grossman, Carsten Krebs, and J. Martin Bollinger, Jr. "Evidence for Modulation of Oxygen-Rebound Rate in Control of Outcome by Iron(II)- and 2-Oxoglutarate-dependent Oxygenases." J. Am. Chem. Soc. 2019, 141 (38), 15153–15165.
  14. S. E. Kearney, G. Zahoránszky-Kőhalmi, K. R. Brimacombe, M. J. Henderson, C. Lynch, T. Zhao, K. K. Wan, Z. Itkin, C. Dillon, M. Shen, D. M. Cheff, T. D. Lee, D. Bougie, K. Cheng, N. P. Coussens, D. Dorjsuren, R. T. Eastman, R. Huang, M. J. Iannotti, S. Karavadhi, C. Klumpp-Thomas, J. S. Roth, S. Sakamuru, W. Sun, S. A. Titus, A. Yasgar, Y.-Q. Zhang, J. Zhao, R. B. Andrade, M. K. Brown, N. Z. Burns, J. K. Cha, E. E. Mevers, J. Clardy, J. A. Clement, P. A. Crooks, G. D. Cuny, J. Ganor, J. Moreno, L. A. Morrill, E. Picazo, R. B. Susick, N. K. Garg, B. C. Goess, R. B. Grossman, C. C. Hughes, J. N. Johnston, M. M. Joullie, A. D. Kinghorn, D. G. I. Kingston, M. J. Krische, O. Kwon, T. J. Maimone, S. Majumdar, K. N. Maloney, E. Mohamed, B. T. Murphy, P. Nagorny, D. E. Olson, L. E. Overman, L. E. Brown, J. K. Snyder, J. A. Porco, Jr., F. Rivas, S. A. Ross, R. Sarpong, I. Sharma, J. T. Shaw, Z. Xu, B. Shen, W. Shi, C. R. J. Stephenson, A. L. Verano, D. S. Tan, Y. Tang, R. E. Taylor, R. J. Thomson, D. A. Vosburg, J. Wu, W. M. Wuest, A. Zakarian, Y. Zhang, T. Ren, Z. Zuo, J. Inglese, S. Michael, A. Simeonov, W. Zheng, P. Shinn, A. Jadhav, M. B. Boxer, M. D. Hall, M. Xia, R. Guha, J. M. Rohde. "Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space." ACS Cent. Sci. 2018, 4 (12), 1727–1741.
  15. Juan Pan, Minakshi Bhardwaj, Bo Zhang, Wei-chen Chang, Christopher L. Schardl, Carsten Krebs, Robert B. Grossman, and J. Martin Bollinger, Jr. "Installation of the ether bridge of lolines by the iron- and 2-oxoglutarate-dependent oxygenase, LolO: regio- and stereochemistry of sequential hydroxylation and oxacyclization reactions." Biochemistry 2018, 57 (14), 2074–2083. ACS Editors' Choice article.
  16. Xing-Wei Yang, Robert B. Grossman, and Gang Xu. "Research Progress of Polycyclic Polyprenylated Acylphloroglucinols." Chem. Rev. 2018, 118 (7), 3508-3558.
  17. Juan Pan, Minakshi Bhardwaj, Padmaja Nagabhyru, Robert B. Grossman, and Christopher L. Schardl. "Enzymes from fungal and plant origin required for chemical diversification of insecticidal loline alkaloids in grass-Epichloë symbiota." PLOS One 2014, 9(12), e115590.
  18. Juan Pan, Minakshi Bhardwaj, Jerome R. Faulkner, Padmaja Nagabhyru, Nikki D. Charlton, Richard M. Higashi, Anne-Frances Miller, Carolyn A. Young, Robert B. Grossman, and Christopher L. Schardl. "Ether bridge formation in loline alkaloid biosynthesis." Phytochemistry 2014, 98, 60–68.
  19. Martin J. Spiering, Jerome R. Faulkner, Dong-Xiu Zhang, Caroline Machado, Robert B. Grossman, and Christopher L. Schardl. "Role of the LolP cytochrome P450 monooxygenase in loline alkaloid biosynthesis." Fungal Genet. Biol. 2008, 45 (9), 1307–1314.
  20. Lynnette M. A. Dirk, Jack J. Schmidt, Yiying Cai, Jonathan C. Barnes, Katherine M. Hanger, Nihar R. Nayak, Mark A. Williams, Robert B. Grossman, Robert L. Houtz, and David W. Rodgers. "Insights into the Substrate Specificity of Plant Peptide Deformylase, an Essential Enzyme with Potential for the Development of Novel Biotechnology Applications in Agriculture." Biochem. J. 2008, 413 (3), 417–427.
  21. Christopher L. Schardl, Robert B. Grossman, Padmaja Nagabhyru, Jerome R. Faulkner, and Uma P. Mallik. "Loline alkaloids: Currencies of mutualism." Phytochemistry 2007, 68 (7), 980–996.
  22. Roxana Ciochina and Robert B. Grossman. "Polycyclic Polyprenylated Acylphloroglucinols." Chem. Rev. 2006, 106 (9), 3963–3986.
  23. Jerome R. Faulkner, Syed R. Hussaini, Jimmy D. Blankenship, Sitaram Pal, Bruce M. Branan, Robert B. Grossman, and Christopher L. Schardl. "On the Sequence of Bond Formation in Loline Alkaloid Biosynthesis." ChemBioChem 2006, 7 (7), 1078–1088.
  24. Raghu Ram Chamala, Roxana Ciochina, Raphael A. Finkel, Robert B. Grossman, Saravana Kannan, and Prasanth Ramachandran. "EPOCH: An Organic Chemistry Homework Program that Offers Response-Specific Feedback." J. Chem. Ed. 2006, 83 (1), 164–169.
  25. Jimmy D. Blankenship, Justin B. Houseknecht, Sitaram Pal, Lowell P. Bush, Robert B. Grossman, and Christopher L. Schardl. "Biosynthetic Precursors of Fungal Pyrrolizidines, the Loline Alkaloids." ChemBioChem 2005, 6 (6), 1016–1022.
  26. Jason T. Brewer, Sean Parkin, and Robert B. Grossman. "A Systematic Study of the Relationship between Molecular and Crystal Structure Among 3,5-Diazabicyclo[2.2.2]octane-2,6-diones." Cryst. Growth Des. 2004, 4 (3), 591–594.
  27. Roxana Ciochina and Robert B. Grossman. "A New Synthetic Approach to the Polyprenylated Polycyclic Acylphloroglucinols." Org. Lett. 2003, 5 (24), 4619–4622.
  28. Shuqian Liu, Hui Huang, Xin Lu, Miroslaw Golinski, Sébastien Comesse, David Watt, Robert B. Grossman, and Jeffrey A. Moscow. "Down-Regulation of Thiamine Transporter THTR2 Gene Expression in Breast Cancer and Its Association With Resistance to Apoptosis." Mol. Cancer Res. 2003, 1 (9), 665–673.
  29. Robert B. Grossman and Ravindra M. Rasne. "Methodology Validation and Structure Correction by Total Synthesis: The Case of the Clerodane Diterpenoid, Sacacarin." In Strategies and Tactics in Organic Synthesis; M. Harmata, Ed.; Elsevier: Amsterdam, 2004; Vol. 4, Chap. 1, pp. 1–18.
  30. Kazuyuki Hattori and Robert B. Grossman. "Functionalized cis- and trans-Fused Bicyclic α-Amino Acids via Stereoselective Double Annulation and Dequaternization Reactions." J. Org. Chem. 2003, 68 (4), 1409–1417.
  31. Robert B. Grossman, Sébastien Comesse, Ravindra M. Rasne, Kazuyuki Hattori, and Matthew N. Delong. "Phosphoramidites are Efficient, Green Organocatalysts for the Michael Reaction. Mechanistic Insights into the Phosphorus-Catalyzed Michael Reaction of Alkynones and Implications for Asymmetric Catalysis." J. Org. Chem. 2003, 68 (3), 871–874.
  32. Robert B. Grossman, Kazuyuki Hattori, Sean Parkin, Brian O. Patrick, and Melissa A. Varner. "The Bicyclic N,N'-Diacylaminal: A New Motif for Molecular Self-Assembly." J. Am. Chem. Soc. 2002, 124 (46), 13686–13687.
  33. Derrick S. Holeman, Ravindra M. Rasne, and Robert B. Grossman. "Trimethylsilylethynyl Ketones as Surrogates for Ethynyl Ketones in the Double Michael Reaction." J. Org. Chem. 2002, 67 (9), 3149–3151.
  34. Robert B. Grossman and Ravindra M. Rasne. "Short Total Syntheses of Both the Putative and Actual Structures of the Clerodane Diterpenoid Sacacarin by Double Annulation." Org. Lett. 2001, 3 (25), 4027–4030.
  35. Freddie Hughes, Jr. and Robert B. Grossman. "A Heterocycle-Forming Double Michael Reaction. [5 + 1] Annulation Route to Highly Substituted and Functionalized Piperidines." Org. Lett. 2001, 3 (18), 2911–2914.
  36. Robert B. Grossman. "The Double Annulation of Tethered Diacids and Alkynones: History and Scope." Synlett 2001 (1), 13–21.
  37. Robert B. Grossman and Helen Jacobs. "On the Structures of Plukenetiones B, D, and E and their Relationships to other Polycyclic Polyprenylated Acylphloroglucinols." Tetrahedron Lett. 2000, 41 (27), 5165–5169.
  38. Robert B. Grossman, Dhananjay S. Pendharkar, Ravindra M. Rasne, and Melissa A. Varner. "Double Annulation Route to Highly Substituted and Functionalized Cis Bicyclic and Tricyclic δ-Lactams and Imides." J. Org. Chem. 2000, 65 (10), 3255–3258.
  39. Robert B. Grossman, Aaron J. Skaggs, Arlene E. Kray, and Brian O. Patrick. "Double Annulation Route to Fused Bicyclic Compounds with Three Contiguous Quaternary Centers." Org. Lett. 1999, 1 (10), 1583–1586.
  40. Melissa A. Varner and Robert B. Grossman. "Annulation Routes to trans-Decalins." Tetrahedron 1999, 55 (49), 13867–13886.
  41. Robert B. Grossman, Dhananjay S. Pendharkar, and Brian O. Patrick. "[n + 1] Annulation Route to Highly Substituted Cyclic Ketones with Pendant Ketone, Nitrile, and Ester Functionality." J. Org. Chem. 1999, 64 (19), 7178–7183.
  42. Robert B. Grossman, Ravindra M. Rasne, and Brian O. Patrick. "Nitro Compounds in the Double Annulation Route to Trans-Fused Bicyclic Compounds." J. Org. Chem. 1999, 64 (19), 7173–7177.
  43. Robert B. Grossman, Melissa A. Varner, and Aaron J. Skaggs. "Double Annulation Route to Highly Substituted and Functionalized Trans-Fused Bicyclic Compounds." J. Org. Chem. 1999, 64 (2), 340–341.
  44. Robert B. Grossman. "Pauson–Khand Approach to Chiral, Diastereomerically Pure Group 4 ansa-Metallocene Complexes." Tetrahedron 1999, 55 (4), 919–934.
  45. Robert B. Grossman and Robert J. Trupp. "The First Reagent-Controlled Asymmetric Halolactonizations. Dihydroquinidine–Halogen Complexes as Chiral Sources of Positive Halogen Ion." Can. J. Chem. 1998, 76 (9), 1233–1237.
  46. Robert B. Grossman and Melissa A. Varner. "Selective Monoalkylation of Diethyl Malonate, Ethyl Cyanoacetate, and Malononitrile Using a Masking Group for the Second Acidic Hydrogen." J. Org. Chem. 1997, 62 (15), 5235–5237.
  47. Robert B. Grossman. "An Essay Assignment for Organic Chemistry Courses." Chem. Educator 1997, 2 (2), S1430-4171(97)02117-1.
  48. Robert B. Grossman. "threo-3,4-Divinyladipic Acid." J. Org. Chem. 1997, 62 (6), 1906–1908.

Books and Software:

  1. Robert B. Grossman. The Art of Writing Reasonable Organic Reaction Mechanisms, Springer.
    • 1st ed., 1999.
    • 2nd ed., 2002.
    • 3rd ed., 2019.
  2. ACE Organic: a Web-based organic chemistry homework program that provides response-specific feedback to structures drawn by students.

Research papers prior to independent career:

  1. Alasdair J. Nisbet, A. Jennifer Mordue (Luntz), Robert B. Grossman, Lyn Jennens, Steven V. Ley, and William Mordue. "Characterization of azadirachtin binding to Sf9 nuclei in vitro." Arch. Insect Biochem. Physiol. 1997, 34 (4), 461-473, and 2001, 46 (1-2), 78-86.
  2. Mariluz L. de la Puente, Robert B. Grossman, Steven V. Ley, Monique S. J. Simmonds, and Wally M. Blaney. "Chemistry of insect antifeedants from Azadirachta indica (Part 20): synthesis of biologically active, simple analogues of azadirachtin, containing the hydroxytetrahydrofurancarboxylate hemiketal moiety." J. Chem. Soc., Perkin Trans. 1 1996, (13), 1517-1521.
  3. Monique S. J. Simmonds, Wally M. Blaney, Steven V. Ley, James C. Anderson, Rolf Bänteli, Alastair A. Denholm, P. Green, Robert B. Grossman, Clare Gutteridge, Lynn Jennens, Stephen C. Smith, Peter L. Toogood, and Anthony Wood. "Behavioural and Neurophysiological Responses of Spodoptera littoralis to Azadirachtin and a Range of Synthetic Analogues." Entomologia Exp. Appl. 1995, 77 (1), 69-80.
  4. Monique S. J. Simmonds, Wally M. Blaney, Robert B. Grossman, and Steven V. Ley. "Behavioural Responses of Locusts and Spodoptera littoralis to Azadirachtin and Azadirachtin Analogues Containing Fluorescent and Immunogenic Reporter Groups." J. Insect Physiol. 1995, 41 (7), 555-564.
  5. Robert B. Grossman and Steven V. Ley. "Chemistry of Insect Antifeedants from Azadirachta indica (Part 17): Synthesis of Model Compounds of Azadirachtin. Unusual Effect of Remote Substituents on the Course of the Oxidative Ring Contraction Reaction." Tetrahedron 1994, 50 (39), 11553-11568.
  6. Robert B. Grossman and Steven V. Ley. "Chemistry of Insect Antifeedants from Azadirachta indica (Part 16): Synthesis of Several Derivatives of Azadirachtin Containing Fluorescent or Immunogenic Reporter Groups." Tetrahedron 1994, 50 (29), 8871-8884.
  7. Robert B. Grossman, Jing-Cherng Tsai, William M. Davis, Alberto Gutiérrez, and Stephen L. Buchwald. "Synthesis and Structure of a C2-Symmetric, Doubly Bridged ansa-Titanocene Complex." Organometallics 1994, 13 (10), 3892-3896.
  8. Scott C. Berk, Robert B. Grossman, and Stephen L. Buchwald. "Development of a Titanocene Catalyzed Enyne Cyclization/ Isocyanide Insertion Reaction." J. Am. Chem. Soc. 1994, 116 (19), 8593-8601.
  9. Scott C. Berk, Robert B. Grossman, and Stephen L. Buchwald. "Titanocene-Catalyzed Conversion of Enynes to Bicyclic Cyclopentenones." J. Am. Chem. Soc. 1993, 115 (11), 4912-4913.
  10. Robert B. Grossman and Stephen L. Buchwald. "Reductive Cyclization of Ester-Containing Enynes with a Practical Titanocene Reagent. Synthesis of Bicyclic Cyclopentenones and Iminocyclopentenes." J. Org. Chem. 1992, 57 (22), 5803-5805.
  11. Robert B. Grossman, William M. Davis, and Stephen L. Buchwald. "Enantioselective, Zirconium-Mediated Synthesis of Allylic Amines." J. Am. Chem. Soc. 1991, 113 (6), 2321-2322.
  12. Robert B. Grossman, Ruth Ann Doyle, and Stephen L. Buchwald. "Syntheses of Ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)zirconium and -hafnium Hydride Complexes. Improved Syntheses of the Corresponding Dichlorides." Organometallics 1991, 10 (5), 1501-1505.
  13. Keith A. Horn, Robert B. Grossman, Jonathan R. G. Thorne, and Anne A. Whitenack. "σ,π* Charge-Transfer Excited States of Substituted (Phenylethynyl)pentamethyldisilanes." J. Am. Chem. Soc. 1989, 111 (13), 4809-4821.
  14. Robert B. Grossman. "Van't Hoff, Le Bel, and the Development of Stereochemistry: A Reassessment." J. Chem. Ed. 1989, 66 (1), 30-33.
  15. Robert A. Pascal, Jr., Robert B. Grossman, and Donna van Engen. "Synthesis of in-[34,10][7]metacyclophane: Projection of an Aliphatic Hydrogen Toward the Center of an Aromatic Ring." J. Am. Chem. Soc. 1987, 109 (22), 6878-6880.
  16. Robert A. Pascal, Jr. and Robert B. Grossman. "A Comment on the Structure and Proton NMR Spectrum of 2,8,17-Trithia[45,12][9]metacyclophane." J. Org. Chem. 1987, 52 (20), 4616-4617.
  17. Keith A. Horn, Robert B. Grossman, and Anne A. Whitenack. "The Palladium Catalyzed Synthesis of Substituted Phenylethynylpentamethyldisilanes and Phenylethynylheptamethyltrisilanes." J. Organomet. Chem. 1987, 332 (3), 271-278.