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Faculty Research

Williams, Lawrence J.

ljwProfessor

Research Synopsis: Computational & experimental mechanistic studies. New reaction discovery and method development. Synthesis of functional materials, including complex bio-active and natural products.

Phone: (848) 445-7916

E-mail: lawjw@chem.rutgers.edu

 

 

 

 

Research Summary

We study molecular structure and reactivity. Our goal is to bring new reactions into the arena of synthetic organic chemistry and to develop superior synthetic strategies. For each reaction a mechanistic framework is established. The transformation is then developed into a preparative method and applied to specific targets, such as to the synthesis of molecules that pose practical or academic problems of structural complexity.

Research in our lab spans organic chemistry and includes the computational and experimental evaluation of reaction mechanism, reactive intermediates, and stereochemistry, the development and application of new and poorly understood reactions, and the integration of knowledge of molecular structure and reactivity into new synthetic strategies for motif building and total synthesis.

Our strategy is to develop a short chemical synthesis to a molecule-type that contains functionality that can be called upon to react along disparate pathways. Such a strategy integrates the routes to multiple targets and thereby allows efficient access - especially in terms of step economy - to large, varied sets of bioactive compounds, including natural products and molecularly edited congeners.

Publications

59. Hoang, T. T.; Dudley, G. B.; Williams, L. J. "Fragmentation Reactions." In Comprehensive Organic Synthesis, 2nd Edition; Molander, G., Knochel, P., Eds.; Elsevier: Oxford, 2014; Vol. 6, Chap. 30, 842.

58. Michael A. Drahl, Madhuri Manpadi and Lawrence J. Williams. "C-C Fragmentation: Origins and Recent Applications." Angew. Chem. Int. Ed. 2013, 52, 11222.

57. Rojita Sharma and Lawrence J. Williams. "Oxetan-3-ones from Allenes via Spirodiepoxides." Org. Lett. 2013, 15, 2202.

56. Kai Liu, Hiyun Kim, Partha Ghosh, Novruz G. Akhmedov and Lawrence J. Williams. "Direct Entry to Erythronlolides via a Cyclic Bis[Allene]." J. Am. Chem. Soc. 2011, 133, 14968.

55. Williams, L. J.; Drahl, M. A.; Manpadi, M. Synthetic Methods and Intermediates for the Preparation of Xenicanes. U.S. Patent Pending, 2011.

54. Williams, L. J.; Liu, K.; Kim, H.; Sharma, R. Macrolide Compounds and Methods and Intermediates Useful for Their Preparation. U.S. Patent Pending, 2011.

53. Da Xu, Michael A. Drahl and Lawrence J. Williams. "Toward an Integrated Route to the Vernonia Allenes and Related Sesquiterpenoids." Beilstein J. Org. Chem. 2011, 7, 937.

52. Rojita Sharma, Madhuri Manpadi, Yue Zhang, Hiyun Kim, Novruz G. Ahmedov and Lawrence J. Williams. "Spirodiepoxide-Based Cascades: Direct Access to Diverse Motifs." Org. Lett. 2011, 13, 3352.

51. Michael A. Drahl, Novruz G. Akhmedov and Lawrence J. Williams. "Selective Conversion of an Enantioenriched Cyclononadienone to the Xeniolide, Xenibellol, and Florlide Cores: An Integrated Routing Strategy." Tetrahedron Lett. 2011, 52, 325.

50. Robert V. Kolakowski and Lawrence J. Williams. "Stereoinduction by Distortional Asymmetry." Nature Chem. 2010, 2, 303.

49. Sipak Joyasawal, Stephen D. Lotesta, N. G. Akhmedov and Lawrence J. Williams. "Spirodiepoxide Strategy to the C Ring of Pectenotoxin 4: Synthesis of the C1-C19 Sector." Org. Lett. 2010, 12, 988.

48. Jongjin Jung, Aniruddh Solanki, Kevin A. Memoli, Ken-ichiro Kamei, Hiyun Kim, Michael A. Drahl, Lawrence J. Williams, Hsian-Rong Tseng and KiBum Lee. "Selective Inhibition of Human Brain Tumor Cells through Multifunctional Quantum-Dot-Based siRNA Delivery." Angew. Chem. Int. Ed. 2010, 49, 103.

47. Partha Ghosh, Joseph R. Cusick, Jennifer Inghrim and Lawrence J. Williams. "Silyl-Substituted Spirodiepoxides: Stereoselective Formation and Regioselective Opening." Org. Lett. 2009, 11, 4672.

46. Yue Zhang, Joseph R. Cusick, Partha Ghosh, Ning Shangguan, Sreenivas Katukojvala, Jennifer Inghrim, Thomas J. Emge and Lawrence J. Williams. "Spirodiepoxides: Synthesis of Epoxomicinoids." J. Org. Chem. 2009, 74, 7707.

45. Partha Ghosh, Yue Zhang, Thomas J. Emge and Lawrence J. Williams. "Modeling a Macrocyclic Bis[spirodiepoxide] Strategy to Erythronolide A." Org. Lett. 2009, 11, 4402.

44. Robert V. Kolakowski, Madhuri Manpadi, Yue Zhang, Thomas J. Emge and Lawrence J. Williams. "Allene Synthesis via C−C Fragmentation: Method and Mechanistic Insight." J. Am. Chem. Soc. 2009, 131, 12910.

43. Yue Zhang, Stephen D. Lotesta, Thomas J. Emge and Lawrence J. Williams. "Structure and Reactivity of a Chiral Cyclononadienone." Tetrahedron Lett. 2009, 10, 1882.

42. Gaojie Hu, Kai Liu and Lawrence J. Williams. "The Brosimum Allene: A Structural Revision." Org. Lett. 2008, 10, 5493.

41. Hiyun Kim and Lawrence J. Williams. "Recent Developments in Allene-based Synthetic Methods." Curr. Opin. Drug Discovery Dev. 2008, 11, 870.

40. Zhenghua Wang, Ning Shangguan, Joseph R. Cusick and Lawrence J. Williams. "Controlled Acid-Induced Rearrangement of a Spirodiepoxide." Synlett 2008, 2, 213.

39. Sezgin Kiren, Ning Shangguan and Lawrence J. Williams. "Direct Carbinolamide Synthesis." Tetrahedron Lett. 2007, 48, 7456.

38. Stephen D. Lotesta, Sezgin Kiren, Ronald R. Sauers and Lawrence J. Williams. "Spirodiepoxides: Heterocycle Synthesis and Mechanistic Insight." Angew. Chem. Int. Ed. 2007, 46, 15.

37. Robert V. Kolakowski and Lawrence J. Williams. "Synthesis of the C21-C28 Segment of Pectenotoxin-4." Tetrahedron Lett. 2007, 48, 4761.

36. Ning Shangguan, Sezgin Kiren and Lawrence J. Williams. "A Formal Synthesis of Psymberin." Org. Lett. 2007, 9, 1093.

35. Partha Ghosh, Stephen D. Lotesta and Lawrence J. Williams. "Spirodiepoxide Reaction with Cuprates." J. Am. Chem. Soc. 2007, 129, 2438.

34. Stephen D. Lotesta, Yongquan Hou and Lawrence J. Williams. "A Spirodiepoxide-Based Strategy to the A-B Ring System of Pectenotoxin 4." Org. Lett. 2007, 9, 869.

33. Robert V. Kolakowski, Ning Shangguan, Ronald R. Sauers and Lawrence J. Williams. "Mechanism of Thio Acid/Azide Amidation." J. Am. Chem. Soc. 2006, 128, 5695.

32. Kristin N. Barlett, Robert V. Kolakowski, Sreenivas Katukojvala and Lawrence J. Williams. "Thio Acid/Azide Amidation: An Improved Route to N-Acyl Sulfonamides." Org. Lett. 2006, 8, 823.

31. Robert V. Kolakowski, Ning Shangguan and Lawrence J. Williams. "Thioamides via Thiatriazolines." Tetrahedron Lett. 2006, 47, 1163.

30. Sezgin Kiren and Lawrence J. Williams. "Configuration of the Psymberin Amide Side Chain." Org. Lett. 2005, 7, 2905.

29. Sreenivas Katukojvala, Kristin N. Barlett, Stephen D. Lotesta and Lawrence J. Williams. “Spirodiepoxides in Total Synthesis: Epoxomicin.” J. Am. Chem. Soc. 2004, 126, 15348.

28. Ning Shangguan, Sreenivas Katukojvala, Rachel Greenberg and Lawrence J. Williams. “The Reaction of Thioacids and Azides: A New Mechanism and New Applications.” J. Am. Chem. Soc. 2003, 125, 7754.

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27. G. Ragupathi, P. O. Livingston, C. Hood, J. Gathuru, S. E. Krown, P. B. Chapman, J. D. Wolchok, L. J. Williams, R. C. Oldrield and W. J. Hwu. “Consistent Antibody Response Against Ganglioside GD2 Induced in Patients with Melanoma by a GD2 Lactone-Keyhole Limpet Hemocyanin Conjugate Vaccine Plus Immunological Adjuvant QS-21.” Clin. Cancer Res. 2003, 9, 5214.

26. B. Jagadish, M. D. Carducci, C. Bosshard, P. Gunter, J. I. Margolis, L. J. Williams and E. A. Mash. "Organic Crystal Engineering with Piperazine-2,5-diones. 4. Crystal Packing of Piperazinediones Derived from 2-Amino-7-cyano-4-methoxyindan-2-carboxylic Acid." Cryst. Growth Des. 2003, 3, 811.

25. G. Ragupathi, D. M. Coltart, L. J. Williams, F. Koide, E. Kagan, J. Allen, C. Harris, P. W. Glunz, P. O. Livingston and S. J. Danishefsky. “On the Power of Chemical Synthesis: Immunological Evaluation of Models for Multiantigenic Carbohydrate-Based Cancer Vaccines.” Proc. Natl. Acad. Sci. USA 2002, 99, 13699.

24. D. M. Coltart, L. J. Williams, P. W. Glunz, D. Sames, S. D. Kuduk, J. Schwarz, X.-T. Chen, R. A. Kumar, S. J. Danishefsky and D. Live. “Principles of Mucin Architecture: Structural Studies on Synthetic Glycopeptides Bearing Clustered Mono-, Di-, Tri- and Hexasaccharide Glycodomains.” J. Am. Chem. Soc. 2002, 124, 9833.

23. G. Ragupathi, P. P. Deshpande, D. M. Coltart, H. M. Kim, L. J. Williams, S. J. Danishefsky and P. O. Livingston. "Constructing an Adenocarcinoma Vaccine: Immunization of Mice with Synthetic KH-1 Nonasaccharide Stimulates Anti-KH-1 and Anti-Ley Antibodies." Int. J. Cancer 2002, 99, 207.

22. T. Gilewski, G. Ragupathi, S. Bhuta, L. J. Williams, X.-F. Zhang, K. P. Bencsath, K. Panagea, J. Chin, L. Norton, A. Houghton, P. O. Livingston and S. J. Danishefsky. "Vaccination of Metastatic Breast Cancer Patients with Globo H Keyhole Limpet Hemocyanin Conjugate Plus the Immunological Adjuvant QS21." Proc. Natl. Acad. Sci. USA 2001, 98, 3270.

21. V. Kudryshov, P. W. Glunz, L. J. Williams, S. Hintermann, S. J. Danishefsky and K. Lloyd. "Epitope Clustering, Carrier Structure, and Adjuvant All Influence Antibody Responses to Lewisy Conjugates in Mice. Implications for the Design of Carbohydrate-Based Cancer Vaccines." Proc. Natl. Acad. Sci. USA 2001, 98, 3264.

20. Z. Wu, L. J. Williams and S. J. Danishefsky. "A Three Step Entry into the Aspirochlorine Class of Anti-Fungal Agents." Angew. Chem. Int. Ed. 2000, 39, 3866.

19. L. J. Williams, C. R. Harris, P. W. Glunz and S. J. Danishefsky "In Pursuit of an Anticancer Vaccine: A Monomolecular Construct Containing Multiple Carbohydrate Antigens." Tetrahedron Lett. 2000, 41, 9505.

18. B. Jagadish, L. J. Williams, M. D. Carducci, C. Bosshard and E. A. Mash. "Organic Crystal Engineering with Piperazine-2,5-diones. 3. Crystal Packing of a Strongly Dipolar Piperazinedione" Tetrahedron Lett. 2000, 41, 9483.

17. P. W. Glunz, S. Hintermann, L. J. Williams, J. B. Schwarz, S. D. Kuduk, V. Kudryshov, K. O. Lloyd and S. J. Danishefsky. “Design and Synthesis of Ley-bearing Glycopeptides that Mimic Cell Surface Mucin Glycoprotein Architecture.” J. Am. Chem. Soc. 2000, 122, 7273.

16. L. J. Williams, R. M. Garbaccio and S. J. Danishefsky. "Iterative Assembly of Glycals and Glycal Derivatives: The Synthesis of Glycosylated Natural Products and Complex Oligosaccharides.” In Carbohydrates in Chemistry and Biology, B. Ernst, G. Hart and P. Sinay, Eds. Wiley-VCH Pub.: Weinheim, Germany, 2000.

15. X. Wang, L. J. Williams, X.-F. Zhang, A. Zatorski, V. Kudryshov, G. Ragupathi, M. Spassova, W. Bornmann, S. F. Slovin, H. I. Scher, P. O. Livingston, K. Lloyd and S. J. Danishefsky. “Polyclonal Antibodies from Patients Immunized with a Globo H-Keyhole Limpet Hemocyanin Vaccine: Isolation, Quantification, and Characterization of Immune Responses by Using Totally Synthetic Immobilized Tumor Antigens.” Proc. Natl. Acad. Sci. USA 2000, 97, 2719.

14. J. Allen, J. Allen, X.-F. Zhang, L. Williams, A. Zatorski, G. Ragupathi, P. O. Livingston and S. J. Danishefsky. “A Second Generation Synthesis of the MBr1 (Globo-H) Breast Tumor Antigen: New Application of the n-Pentenyl Glycoside Method for Achieving Complex Carbohydrate Protein Linkages.” Chem. Eur. J. 2000, 6, 1366.

13. P. Glunz, S. Hintermann, J. Schwarz, S. Kuduk, X. Chen, L. Williams, D. Sames, S. J. Danishefsky, V. Kudryshov and K. Lloyd. “Probing Cell-Surface ‘Glyco-Achitecture’ through Total Synthesis. Immunological Consequences of a Human Blood Group Determinant in a Clustered Munic-Like Motif.” J. Am. Chem. Soc. 1999, 121, 10636.

12. D. H. Live, R. A. Kumar, L. J. Williams and D. Sames. “Insights into Glycoproteins - A Structural Motif for Mucins from a Glycopeptide.” In Peptides for the New Millennium: Proceedings of the 16th American Peptide Symposium, G.B. Fields, J. P. Tam and G. Barany, Eds. Kluwer Academic Pub.: Dordecht, Holland, 1999.

11. L. J. Williams, B. Jagadish, M. G. Lansdown, M. D. Carducci and E. A. Mash. “Organic Crystal Engineering with Piperazine-2,5-diones. 2. Crystal Packing of Weakly Dipolar Piperazinediones Derived from 2-Amino-4-bromo-7-methoxyindan-2-carboxylic Acids." Tetrahedron 1999, 55, 14301.

10. L. J. Williams, B. Jagadish, S. R. Lyon, R. A. Kloster, M. D. Carducci and E. A. Mash. “Organic Crystal Engineering with Piperazine-2,5-diones. 1. Crystal Packing of Piperazinediones Derived from Substituted 2-Aminoindan-2-carboxylic Acids." Tetrahedron 1999, 55, 14281.

9.   D. Live, L. Williams, S. Kuduk, J. Schwarz, P. Glunz, X.-T. Chen, D. Sames, R. A. Kumar and S. J. Danishefsky. “Probing Cell-Surface Architecture through Synthesis: An NMR Determined Structural Motif for Tumor Associated Mucins.” Proc. Natl. Acad. Sci. USA 1999, 96, 3489.

8.   L. J. Williams, K. Kather and D. S. Kemp. “High Helicities of Lys Containing, Ala-Rich Peptides Are Primarily Attributable to a Large, Context-Dependent Lys Stabilization.” J. Am. Chem. Soc. 1998, 120, 11033.

7.   E. A. Mash, L. Williams and S. S. Pfeiffer. “Synthesis of Ethyl N-(diphenyl)methyl-1-2-3-4 Tetrahydroisoquinoline-3-carboxylates.” Tetrahedron Lett. 1997, 38, 6977.

6.   E. A. Mash and L. Williams. “Engineering Molecular Solids.” Polymer Preprints 1996, 37, 207.

5.   Danishefsky, S. J.; Sames, D.; Hintermann, S.; Chen, X. T.; Schwartz, J. B.; Glunz, P.; Ragupathi, G.; Livingston, P. O.; Kuduk S.; Lloyd, K. O.; Kudryashov, V.; Williams, L. J.  Trimeric Antigenic O-Linked Glycopeptide Conjugates, Methods of Preparation and Uses Thereof.  European Patent: WO9948515, 1999.

4.   Danishefsky, S. J.; Lloyd, K. O.; Wang, Z.-G.; Williams, L. J.  Affinity Matrix Bearing Tumor-Associated Antigens. European Patent:  WO0165261, 2001.

3.   Danishefsky, S. J.; Sames, D.; Hintermann, S.; Chen, X. T.; Schwarz, J. B.; Glunz, P.; Ragupathi, G.; Livingston, P. O.; Kuduk, S.; Williams, L. J.  α-O-Linked Glycoconjugates, Methods of Preparation and Uses Thereof.  U.S. Patent 6,660,714, 2003.

2.   Danishefsky, S. J.; Sames, D.; Hintermann, S.; Chen, X. T.; Schwarz, J. B.; Glunz, P.; Ragupathi, G.; Livingston, P. O.; Kuduk, S.; Williams, L. J.  α-O-Linked Glycoconjugates, Methods of Preparation and Uses Thereof.  U.S. Patent 7,160,856, 2007.

1.   Danishefsky, S. J.; Allen, J. R.; Ragupathi, G.; Livingston, P. O.; Williams, L. J.  Novel Glycoconjugates, Glycoamino Acids, Intermediates Thereto, and Uses Thereof.  European Patent: DE60027905T, 2007.

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