Synthesis of Some New Spiro β-Lactams and Thiazolidinones Compounds Containing Sulfur Incorporating Quinon Compounds


A series of spiro, β-Lactams, and thiazolidinones incorporating compounds 4 have been synthesized by cycloaddition reaction of, chloroacetyl chloride and mercaptoacetic acid with the synthesized Shiff,s bases 5a-c to give new spiro β- Lactam 6a-c and spiro thiazolidinone 7a-c the cycloaddition were characterized by spectral data including HNMR, 13C-NMR, IR and elemental analysis.

Share and Cite:

N. Elkanzi, "Synthesis of Some New Spiro β-Lactams and Thiazolidinones Compounds Containing Sulfur Incorporating Quinon Compounds," International Journal of Organic Chemistry, Vol. 2 No. 4, 2012, pp. 352-361. doi: 10.4236/ijoc.2012.24048.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. Southgate, “The Synthesis of Natural β-Lactam Antibiotics,” Contemporary Organic Synthesis, Vol. 1, No. 6, 1994, pp. 417-431. doi:10.1039/co9940100417
[2] F. Broccolo, G. Carnally, G. Caltabiano, C. E. A. Cocuzza, C. Fortuna, G. Galletti, P. D. Giacomini, G. Musumarra, R. Musumeci and A. Quitavalla, “Design, Synthesis, and Biological Evaluation of 4-Alkyliden-Beta Lactams: New Products with Promising Antibiotic Activity against resIstant Bacteria,” Journal of Medicinal Chemistry, Vol. 49, No. 9, 2006, pp. 2804-2811. doi:10.1021/jm0580510
[3] B. Alcaide, P. Almendros and C. Aragoncillo, “β-Lactams: Versatile Building Blocks for the Stereoselective Synthesis of Non-β-Lactam Products,” Chemical Reviews, Vol. 107, 2007, pp. 4437-4492.
[4] B. Alcaide and P. Almendros, “β-Lactams as Versatile Intermediates for the Preparation of Heterocycles of Biological Interest,” Current Medicinal Chemistry, Vol. 11, No. 14, 2004, pp. 1921-1949. doi:10.2174/0929867043364856
[5] A. R. A. S. Deshmukh, B. M. Bhawal, D. Krishnaswamy, V. V. Govande, B. A. Shinkre and A. Jayanthi, “Azetidin-2-Ones, Synthon for Biologically Important Compounds,” Current Medicinal Chemistry, Vol. 11, No. 14. 2004, pp. 1889-1920. doi:10.2174/0929867043364874
[6] B. Alcaide and P. Almendros, “Selective Bond Cleavage of the β-Lactam Nucleus: Application in Stereocontrolled Synthesis,” Synlett, Vol. 3, 2002, pp. 381-393. doi:10.1055/s-2002-20448
[7] C. Palomo, J. M. Aizpurua, I. Ganboa and M. Oiarbide, “β-lactams as Versatile Intermediates in α- and β-Amino Acid Synthesis,” Synlett, Vol. 12, 2001, pp. 1813-1826. doi:10.1055/s-2001-18733
[8] I. Ojima, “The Organic Chemistry of β-Lactams,” G. I. Georg, Ed., VCH, New York, 1993, pp. 197-255.
[9] I. Ojima, “Recent Advances in the β-Lactam Synthon Method,” Accounts of Chemical Research, Vol. 28, No. 9, 1995, pp. 383-389. doi:10.1021/ar00057a004
[10] M. O’Driscoll, K. Greenhalgh, A. Young, E. Turos, S. Dickey and D. V. Lim, “Studies on the Antifungal Properties of N-Thiolated β-Lactams,” Bioorganic & Medicinal Chemistry, Vol. 16, No. 16, 2008, pp. 7832-7837. doi:10.1016/j.bmc.2008.06.035
[11] E. Turos, G. S. K. Reddy, K. Greenhalgh, P. Ramaraju, S. C. Abeylath, S. Jang, S. Dickey and D. V. Lim, “Penicillin-Bound Polyacrylate Nanoparticles: Restoring the Activity of β-Lactam Antibiotics against MRSA,” Bioorganic & Medicinal Chemistry Letters, Vol. 17, No. 12, 2007, pp. 3468-3472. doi:10.1016/j.bmcl.2007.03.077
[12] S. Dugar, N. Yumibe, J. W. Clader, M. Vizziano, K. Huie, M. van Heek, D. S. Compton and H. R. Davis Jr., “Metabolism and Structure Activity Data Based Drug Design: Discovery of (?) SCH53079 an Analog of the Potent Cholesterol Absorption Inhibitor (?) SCH 48461,” Bioorganic & Medicinal Chemistry Letters, Vol. 6, No. 11, 1996, pp. 1271-1274. doi:10.1016/0960-894X(96)00214-4
[13] W. T. Han, A. K. Trehan, J. J. K. Wright, M. E. Federici, S. M. Seiler and N. A. Meanwell, “Azetidin-2-One Derivatives as Inhibitors of Thrombin,” Bioorganic & Medicinal Chemistry, Vol. 3, No. 8, 1995, pp. 1123-1143. doi:10.1016/0968-0896(95)00101-L
[14] A. D. Borthwick, G. Weingarte, T. M. Haley, M. Tomaszewski, W. Wang, Z. Hu, J. Bedard, H. Jin, L. Yuen and T. S. Mansour, “Design and Synthesis of Monocyclic β-Lactams as Mechanismbased Inhibitors of Human Cytomegalovirus Protease,” Bioorganic & Medicinal Chemistry Letters, Vol. 8, No. 4, 1998, pp. 365-370. doi:10.1016/S0960-894X(98)00032-8
[15] G. Cainelli, P. Galletti, S. Garbisa, D. Giacomini and L.Sartor, “Quintavalla, A. 4-Alkylideneazetidin-2-Ones: Novel Inhibitors of Leukocyte Elastase and Gelatinase,” Bioorganic & Medicinal Chemistry, Vol. 11, No. 24, 2003, pp. 5391-5399. doi:10.1016/j.bmc.2003.09.035
[16] N. E. Zhou, D. Guo, G.Thomas, A. V. N. Reddy, J. Kaleta, E. Purisima, R. Menard, R. G. Micetich and R. Singh, “3-Acylamino-Azetidin-2-One as a Novel Class of Cysteine Proteases Inhibitors,” Bioorganic & Medicinal Chemistry Letters, Vol. 13, No. 1, 2003, pp. 139-141. doi:10.1016/S0960-894X(02)00831-4
[17] A. Kazi, R. Hill, T. E. Long, D. J. Kuhn, E. Turos and Q. P. Dou, “Novel N-Thiolated β-Lactam Antibiotics Selectively Induce Apoptosis in Human Tumor and Transformed, but Not Normal or Nontransformed, Cells,” Biochemical Pharmacology, Vol. 67, No. 2, 2004, pp. 365-374. doi:10.1016/j.bcp.2003.09.017
[18] E. Alonso, F. Lopez-Ortiz, C. Del Pozo, E. Peratta, A. Macias and J. Gonzalaz, “Spiro β-Lactams as β-Turn Mimetics. Design, Synthesis, and NMR Conformational Analysis,” The Journal of Organic Chemistry, Vol. 66, No. 19, 2001, pp. 6333-6338. doi:10.1021/jo015714m
[19] H. Bittermann and P. Gmeiner, “Chirospecific Synthesis of Spirocyclic β-Lactams and Their Characterization as Potent Type ii β-Turn Inducing Peptide Mimetics,” The Journal of Organic Chemistry, Vol. 71, No. 1, 2006, pp. 97-102. doi:10.1021/jo0517287
[20] E. Alonso, C. Del Pozo and J. Gonzalez, “Synthesis of α,α-Disubstituted β-Amino Esters and Peptide Derivatives,” Synlett, Vol. 1, 2002, pp. 69-72. doi:10.1055/s-2002-19326
[21] J. L. Pinder and S. M. Weinreb, “Preliminary Feasibility Studies on Total Synthesis of the Unusual Marine Bryozoan Alkaloids Chartellamide A and B,” Tetrahedron Letters, Vol. 44, No. 21, 2003, pp. 4141-4143. doi:10.1016/S0040-4039(03)00876-1
[22] J. W. Skiles and D. McNeil, “Spiro Indolinone Beta-Lactams, Inhibitors of Poliovirus and Rhinovirus 3c-Proteinases,” Tetrahedron Letters, Vol. 31, No. 50, 1990, pp. 7277-7280. doi:10.1016/S0040-4039(00)88543-3
[23] A. Jarrahpour and D. Khalili, “Synthesis of Some Mono- and Bis-Spiro-β-Lactams of Benzylisatin,” Tetrahedron Letters, Vol. 48, No. 40, 2007, pp. 7140-7143. doi:10.1016/j.tetlet.2007.07.199
[24] X. Lin and S. M. Weinreb, “Model Studies on Total Synthesis of the Chartellines, Spirocyclic β-Lactam Alkaloids from a Marine Bryozoan,” Tetrahedron Letters, Vol. 42, No. 14, 2001, pp. 2631-2633. doi:10.1016/S0040-4039(01)00270-2
[25] S. Anklam and J. Liebscher, “Synthesis of Optically Active Spiro-β-Lactams by Cycloadditions to α-Alkylidene- β-Lactams,” Tetrahedron, Vol. 54, No. 23, 1998, pp. 6369-6384. doi:10.1016/S0040-4020(98)00296-8
[26] B. Alcaide, P. Almendros, T. M. Del Campo, R. Rodríguez-Acebes, “Diversity-Oriented Preparation of Enantiopure Spirocyclic 2-Azetidinones from α-Oxo-β-Lactams through Barbier-Type Reactions Followed by Metal-Catalyzed Cyclizations,” Advanced Synthesis & Catalysis, Vol. 349, No. 4-5, 2007, pp. 749-758. doi:10.1002/adsc.200600502
[27] A. Gareth, C. Jonathan and D. H. Stuart, “Azabicyclic Amino Acids by Stereoselective Dearomatizing Cyclization of the Enolates of N-Nicotinoyl Glycine Derivatives,” Organic Letters, Vol. 8, No. 23, 2006, pp. 5325- 5328. doi:10.1021/ol062126s
[28] A. Bhalla, P. Venugopalan and S. S. Bari, “A New Synthetic Approach to Novel Spiro-β-Lactams,” European Journal of Organic Chemistry, Vol. 2006, No. 21, 2006, pp. 4943-4950. doi:10.1002/ejoc.200600458
[29] A. Zanobini, A. Brandi and A. De Meijere, “A New Three-Component Cascade Reaction to Yield 3-Spirocyclopropanated β-Lactams,” European Journal of Organic Chemistry, Vol. 2006, No. 5, 2006, pp. 1251-1255. doi:10.1002/ejoc.200500838
[30] A. Zanobini, M. Gensini, J. Magull, D. Vidovic, S. I. Kozhushkov, A. Brandi and A. De Meijere, “A Convenient New Synthesis of 3-Substituted β-Lactams Formally Derived from 1-(Aminomethyl)cyclopropanecarboxylic acids,” European Journal of Organic Chemistry, Vol. 2004, No. 20, 2004, pp. 4158-4166. doi:10.1002/ejoc.200400392
[31] B. Alcaide, P. Almendros and R. Rodríguez-Acebes, “Pd-Cu Bimetallic Catalyzed Domino Cyclization of α-Allenols Followed by a Coupling Reaction: New Sequence Leading to Functionalized Spirolactams,” Chemistry of the European Journal, Vol. 11, No. 19, 2005, pp. 5708-5712. doi:10.1002/chem.200500228
[32] A. Bhalla, P. Venugopalan, K. K. Bhasin and S. S. Bari, “Seleno-β-Lactams: Synthesis of Monocyclic and Spirocyclic Selenoazetidin-2-Ones,” Tetrahedron, Vol. 63, No. 15, 2007, pp. 3195-3204. doi:10.1016/j.tet.2007.02.001
[33] C. V. Galliford, J. S. Martenson, C. Stern and K. A. Scheidt, “A Highly Diastereoselective, Catalytic three- Component Assemblyreaction for the Synthesis of Spiropyrrolidinyloxindoles,” Chemical Communications, Vol. 2007, No. 6, 2007, pp. 631-633. doi:10.1039/b609155e
[34] C. Sun, X. Lin and M. Weinreb, “Explorations on the Total Synthesis of the Unusual Marine Alkaloid Chartelline A,” The Journal of Organic Chemistry, Vol. 71, No. 8, 2006, pp. 3159-3166. doi:10.1021/jo060084f
[35] B. Alcaide, P. Almendros and R. Rodr?′guez-Acebes, “Efficient Entry to Diversely Functionalized Spirocyclic Oxindoles from Isatins through Carbonyl-Addition/Cyclization Reaction Sequences,” The Journal of Organic Chemistry, Vol. 71, No. 6, 2006, pp. 2346-2351. doi:10.1021/jo0525027
[36] G. Cremonesi, P. Dalla Croce and C. La Rosa, “Synthesis of Imidazo[5,1-b]thiazoles or Spiro-β-Lactams by Reaction of Imines with Mesoionic Compounds or Ketenes Generated from N-Acylthiazolidine-2-Carboxylic Acids,” Tetrahedron, Vol. 60, No. 1, 2004, pp. 93-97. doi:10.1016/j.tet.2003.10.093
[37] B. Alcaide, P. Almendros, T. M. Del Campo and R. Rodr?′guez-Acebes, “Metal-Assisted Synthesis of Enantiopure Spirocyclic β-Lactams from Azetidine-2,3- Diones,” Tetrahedron Letters, Vol. 45, No. 34, 2004, pp. 6429-6431. doi:10.1016/j.tetlet.2004.06.130
[38] N. Toshio, K. Shigeo and I. Minoru, “Novel Synthesis of Bromoindolenine with Spiro-Blactam in Chartelline,” Synlett, Vol. 2004, 2004, pp. 2025-2027.
[39] O. Arjona, A. G. Csa`ky, M. C. Murcia and J. Plumet, “The Staudinger Reaction of Imines derived from 7-Oxanorbornenone: Formation of Spiranic Oxazinone versus β-Lactam Rings,” Tetrahedron Letters, Vol. 43, No. 36, 2002, pp. 6405-6408. doi:10.1016/S0040-4039(02)01375-8
[40] E. Alonso, C. Del Pozo and J. Gonzalez, “Staudinger Reactions of Unsymmetrical Cyclic Ketenes: A Synthetically Useful Approach to Spiro β-Lactams and Derivatives. Reaction Mechanism and Theoretical Studies,” Journal of the Chemical Society, Perkin Transactions, Vol. 1, No. 4, 2002, pp. 571-576. doi:10.1039/b103279h
[41] I. R. Cooper, R. Grigg, W. S. MacLachlan and M. Thornton-Pett, V. Sridharane, “3-Component Palladium-Indium Mediated Diastereoselective Cascade Allylation of Imines with Allenes and Aryl Iodides,” Chemical Communications, Vol. 13, 2002, pp. 1372-1373. doi:10.1039/b202940e
[42] C. Palomo, J. M. Aizpurua, I. Ganboa and M. Oiarbide, “Asymmetric Synthesis of β-Lactams through the Staudinger Reaction and Their Use as Building Blocks of Natural and Nonnatural Products,” Current Medicinal Chemistry, Vol. 11, No. 14, 2004, pp. 1837-1872. doi:10.2174/0929867043364900
[43] I. Banik, F. F. Becker and B. K. Banik, “Stereoselective Synthesis of β-Lactams with Polyaromatic Imines: Entry to New and Novel Anticancer Agents,” Journal of Medicinal Chemistry, Vol. 46, No. 1, 2003, pp. 12-15. doi:10.1021/jm0255825
[44] B. K. Banik, F. F. Becker and I. Banik, “Synthesis of Anticancer β-Lactams: Mechanism of Action,” Bioorganic & Medicinal Chemistry, Vol. 12, No. 10, 2004, pp. 2523-2528. doi:10.1016/j.bmc.2004.03.033
[45] F. F. Becker and B. K. Banik, “Polycyclic Aromatic Compounds as Anticancer Agents: Synthesis and Biological Evaluation of Some Chrysene Derivatives,” Bioorganic & Medicinal Chemistry Letters, Vol. 8, No. 20, 1998, pp. 2877-2880. doi:10.1016/S0960-894X(98)00520-4
[46] A. K. Khalafallah, R. M. Abdel Aal and N. A. A. Elkanzi “Synthesis of Some New Fused/Spiro Heterocyclic Compound Incorporating Quinone Compounds,” Journal of the Chinese Chemical Society, Vol. 49, 2002, pp. 387- 696.
[47] N. A. A. Elkanzi, A. K. Khalafallah and M. Younis, “Effect of Iodine on the Antimicrobial Activity of New Spiro and Isolated β-Lactam Thiazolidinone Derivatives,” Phosphorus, Sulfur and Silicon, Vol. 182, 2007, pp. 1163-1181.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.