Rohidas M. Jagtap¹, Sachin S. Sakate¹, Satish K. Pardeshi² and Masood A. Rizvi³
¹Department of Chemistry, P. E. S. Modern College of Arts, Science and Commerce, Shivajinagar (Autonomous), Pune, MS, India
²Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, MS, India
³Department of Chemistry, University of Kashmir, Hazratbal, Srinagar, Jammu and Kashmir, India

Part of the book: Advances in Chemistry Research. Volume 76

Abstract

The natural α-amino acids are the ample chiral precursors for the target synthesis of variety of bioactive moieties. In the conversion of a α-amino acid to another bioactive molecule, the chirality of α carbon is maintained and a new chiral center with the different or retained stereochemistry is added to the parent structure. The thiazolidine class of the compounds are synthesized from L-Cysteine natural amino acid and exhibits a broad spectrum of the biological activities. L-Cysteine amino acid undergoes the nucleophilic cyclization with aliphatic and aromatic aldehydes to form diasteromeric (2R,4R)-2-alkyl/aryl thiazolidine-4-carboxylic acids and (2S,4R)-2-alkyl/aryl thiazolidine-4-carboxylic acids (2A-T4CA) respectively. In order to synthesize these chiral 2A-T4CA moieties, numerous efforts are deliberated by various worldwide research groups. The chronological developments of several synthetic protocols for the synthesis of T4CA derivatives along with the mechanistic investigations are summarized in the present chapter. There are several studies reported in the literature which are deliberated towards the antioxidant and antibacterial studies of these thiazolidine derivatives. These antioxidant and antibacterial studies are also conversed in this chapter in a structure-activity perspective.

References

[1] Fromm, H. J. and Hargrove, M. (2012). Essentials of Biochemistry, Springer-Verlag,
Berlin, Heidelberg, Ch. 5, 5-11.
[2] Drauz, K., Grayson, I., Kleemann, A., Krimmer, H-P., Leuchtenberger, W. and
Weckbecker, C. (2007). Ullmann’s Encyclopedia of Industrial Chemistry, Wiley‐
VCH, Weinheim, Germany, 3, 1-58.
[3] Vallee, Y., Shalayel, I., Ly, K. D., Rao, K. V. R., Paepe, G. D., Marker, K. and Milet,
A. (2017). At the very beginning of life on Earth: the thiol-rich peptide (TRP) world
hypothesis. International Journal of Developmental Biology, 61, 8-9.
[4] Sevier, C. S. and Kaiser, C. A. (2002). Formation and transfer of disulphide bonds
in living cells. Nature Reviews Molecular Cell Biology, 3, 836-847.
[5] Sprince, H., Parker, C. M., Smith, G. G. and Gonzales, L. J., (1974). Protection
against acetaldehyde toxicity in the rat by L-cysteine, thiamin and L-2-
methylthiazolidine-4-carboxylic acid. Agents Actions, 2, 125-130.
[6] Schubert, M. P. (1936). Compounds of thiol acids with aldehydes, Journal of
Biological Chemistry, 114, 341-350.
[7] Ratner, S. and Clarke, H. C. (1937). The action of formaldehyde on cysteine, Journal
of American Chemical Society, 59, 200-206.
[8] Lieberman, S., Brazeau, P. and Hariton, L. B. (1948). Spiro(Steroid)Thiazolidines,
Journal of American Chemical Society, 70, 3094-3097.
[9] Soloway, H., Kipnis, F., Ornfelt, J. and Spoerri, P. E. (1948). 2-alkyl-substituted thiazolidine-4-carboxylic Acids, Journal of American Chemical Society, 70, 1667-1668.
[10] Wiley, R. H. and Jeffries, J. F. (1949). 2,2-Disubstituted-thiazolidine-4-carboxylic
Acids, Journal of American Chemical Society, 71, 1137.
[11] Ikawa, M. and Snell, E. E. (1954). Benzene Analogs of Pyridoxal. The Reactions of
4-Nitrosalicylaldehyde with Amino Acids, Journal of American Chemical Society,
76, 653-655.
[12] Schmolka, I. R. and Spoerri, P. E. (1957). The Preparation of 2-Substituted
Thiazolidine-4-carboxylic Acids, Journal of Organic Chemistry, 76, 943-946.
[13] Ostrovskaya, Y. A., Adamovich, A. I., Argitti, M. G. and Naidis, F. B. (1970).
Improving the production process for the synthesis of leucogen, Pharmaceutical
Chemistry Journal, 4, 3, 167-168.
[14] Paul, B. and Korytnyk, W. (1976). Cysteine Derivatives with Reactive Groups as
Potential Antitumor Agents, Journal of Medicinal Chemistry, 19, 8, 1002-1007.
[15] Gyorgydeak, Z., Kajtar-Peredy, M., Kajtar, J. and Kajtar, M. (1987). Synthese und
chiroptische Eigenschaften von N-Acetyl-4-thiazolidincarbonsauren, Justus Liebigs
Annalen der Chemie, 11, 927-934.
[16] Radomski, J. and Temeriusz, A. (1989). Thiazolidine-4(R)-carboxylic acids derived
from sugars: Part I, C-2-epimerisation in aqueous solutions, Carbohydrate
Research, 187, 223-237.
[17] Ferraboschi, P., Grisenti, P., Santaniello, E., Giachetti, C., Zanolo, G., Signorelli, G
and Coppi, G. (1992). Synthesis of the new immunostimulating agent pidotimod (3-
L-pyroglutamyl-L-thiazolidine-4-carboxylic acid) labelled with 14C- and 35S isotopes, Journal of Labelled Compounds and Radiopharmaceuticals, 31, 973-980.
[18] Yin, H., Crowder, R. J., Jones, J. P. and Anders, M. W. (1996). Reaction of
Trifluoroacetaldehyde with Amino Acids, Nucleotides, Lipid Nucleophiles, and
Their Analogs, Chemical Research in Toxicology, 9, 140-146.
[19] Starkenmann, C. (2003). Analysis of a Model Reaction System Containing Cysteine
and (E)-2-Methyl-2-butenal, (E)-2-Hexenal, or Mesityl Oxide, Journal of
Agricultural and Food Chemistry, 51, 7146-7155.
[20] Saiz, C., Wipf, P., Manta, E. and Mahler, G. (2009). Reversible Thiazolidine
Exchange: A New Reaction Suitable for Dynamic Combinatorial Chemistry,
Organic Letters, 1115, 3170-3173.
[21] Rambo, R. S. and Schneider, P. H. (2010). Thiazolidine-based organocatalysts for a
highly enantioselective direct aldol reaction, Tetrahedron: Asymmetry, 21, 2254-2257.
[22] Rodriguez-Salus, M., Bektas, Y., Schroeder, M., Knoth, C., Vu, T., Roberts, P.,
Kaloshian, I. and Eulgem, T. (2016). The Synthetic Elicitor 2-(5-Bromo-2-Hydroxy Phenyl)-Thiazolidine-4-Carboxylic Acid Links Plant Immunity to Hormesis, Plant
Physiology, 170, 444-458.
[23] Szilagyi, L. and Gyorgydeak, Z. (1979). Comments on the putative stereoselectivity
in cysteine-aldehyde reactions, Selective C(2) inversion and C(4) epimerization in
thiazolidine-4-carboxylic acids, Journal American Chemical Society, 101, 427-432.
[24] Herak, J. J., Kovacevic, M. and Gaspert, B. (1979). Epimerisation of 2-substituted
5,5-dimethyl-thiazolidine-4-Cahboxylic acid, Phosphorus and Sulfur, 6, 131.
[25] Roberts, J. C., Nagasawa, H. T., Zera, R. T., Fricke, R. F. and Goon, D. J. W. (1987).
Prodrugs of L-Cysteine as Protective Agents against Acetaminophen-Induced
Hepatotoxicity. 2-(Polyhydroxyalkyl)- and 2-(Polyacetoxyalkyl)thiazolidine-4(R)-
carboxylic Acids, Journal of Medicinal Chemistry, 30, 1891-1896.
[26] Jagtap, R. M., Rizvi, M. A., Dangat, Y. B. and Pardeshi, S. K. (2016). Crystal
structure, computational studies, and stereoselectivity in the synthesis of 2-aryl thiazolidine-4-carboxylic acids via in situ imine intermediate, Journal of Sulfur
Chemistry, 37, 4, 401-425.
[27] Nagasawa, H. T., Goon, D. J. W., Muldoon, W. P. and Zerat, R. T. (1984). 2-
Substituted Thiazolidine-4(R)-carboxylic Acids as Prodrugs of L-Cysteine.
Protection of Mice against Acetaminophen Hepatotoxicity, Journal Medicinal
Chemistry, 27, 591-596.
[28] Ikunaka, M., Matsumoto, J. and Nishimoto, Y. (2002). A concise synthesis of
(2S,3S)-BocAHPBA and (R)-BocDMTA, chiral building blocks for peptide mimetic HIV protease inhibitors, Tetrahedron: Asymmetry, 13, 1201-1208.
[29] Koide, Y., Hasegawa, T., Takahashi, A., Endo, A., Mochizuki, N., Nakagawa, M.
and Nishida, A. (2002). Development of Novel EDG3 Antagonists Using a 3D
Database Search and Their Structure-Activity Relationships, Journal Medicinal
Chemistry, 45, 4629-4638.
[30] Lee, K. S., Park, H. S., Park, S. J., Kim, S. R., Min, K. H., Jin, S. M., Park, K-H,
Kim, U. H, Kim, C. Y. and Lee, Y. C., (2005). A Prodrug of Cysteine, L-2-
Oxothiazolidine-4-carboxylic Acid, Regulates Vascular Permeability by Reducing
Vascular Endothelial Growth Factor Expression in Asthma, Molecular
Pharmacology, 68, 281-1290.
[31] Jin, C., Burgess, J. P., Gopinathan, M. B. and Brine, G. A. (2006). Chemical
synthesis and structural elucidation of a new serotonin metabolite: (4R)-2-[(50-
hydroxy-10H-indol-30-yl)-methyl]thiazolidine-4-carboxylic acid, Tetrahedron
Letters, 47, 943-946.
[32] Liu, Y., Jing, F., Xu, Y., Xie, Y., Shi, F., Fang, H., Li, M. and Xu, W. (2011). Design,
synthesis and biological activity of thiazolidine-4-carboxylic acid derivatives as
novel influenza neuraminidase inhibitors, Bioorganic Medical Chemistry Letters,
19, 2342-2348.
[33] Ha, Y. M., Park, Y. J., Lee, J. Y., Park, D., Choi, Y. J., Lee, E. K., Kim, J. M., Kim,
J. A., Park, J. Y., Lee, H. J., Moon H. R. and Chunga, H. Y. (2012). Design, synthesis
and biological evaluation of 2-(substituted phenyl)thiazolidine-4-carboxylic acid
derivatives as novel tyrosinase inhibitors, Biochimie, 94, 533-540.
[34] Chen, P., Horton, L. B., Mikulski, R. L., Deng, L., Sundriyal, S., Palzkill, T. and
Song, Y. (2012). 2-Substituted 4,5-dihydrothiazole-4-carboxylic acids are novel
inhibitors of metallo-β-lactamases, Bioorganic and Medicinal Chemistry Letters,
22, 6229-6232.
[35] Frimayanti, N., Lee, V. S., Zain, S. M., Wahab, H. A. and Rahman, A. (2024). 2D,
3D-QSAR and pharmacophore studies on thiazolidine-4-carboxylic acid derivatives
as neuraminidase inhibitors in H3N2 influenza virus, Medicinal Chemistry
Research, 23, 1447-1453.
[36] Lee, B., Moon, K. M., Son, S., Yun, H. Y., Han, Y. K., Ha, Y. M., Kim, D. H.,
Chung, K. W., Lee, E. K., An, H. J., Ullah, S., Chun, P., Moon, H. R. and Chung,
H. Y. (2015). (2R/S,4R)-2-(2,4-Dihydroxyphenyl)thiazolidine- 4-carboxylic acid
prevents UV-induced wrinkle formation through inhibiting NF-kB-mediated
inflammation, Journal of Dermatological Science, 79, 3, 313-316.
[37] Corvino, A., Severino, B., Fiorino, F., Frecentese, F., Magli, E., Perissutti, E.,
Santagada, V., Bucci, M., Cirino, G., Kelly, G., Servillo, L., Popowicz, G., Pastore,
A. and Caliendo, G. (2017). Fragment-based de novo design of a cystathionine γ-
lyase selective inhibitor blocking hydrogen sulfide production, Scientific Reports,
2017, 6, 34398-34408.
[38] Khan, J. A., Wahab, A-T., Javaid, S., Al-Ghamdi, M., Huwait, E., Shaikh, M.,
Shafqat, A. and Choudhary, M. I. (2017). Studies on new urease inhibitors by using
biochemical, STD-NMR spectroscopy, and molecular docking methods, Medicinal
Chemistry Research, 26, 2452-2467.
[39] Nagasree, K. P., Kumar, M. M. K., Prasad, Y. R., Sriram, D. and Yogeeswari, P.
(2018). Synthesis and in vitro studies of thiazolidine-4-carboxylic acid hydrazones
as potential antitubercular agents, Indian Journal of Chemistry, Section B, 57B, 4,
538-555.
[40] Bozovic, V. and Enesco, H. E. (1986). Effect of antioxidants on rotifer lifespan and
activity, Age, 9, 41-45.
[41] Wlodek, L. and Rommelspacher, H. (1994). Ethanol-induced changes in the content
of thiol compounds and of lipid peroxidation in livers and brains from mice:
protection by thiazolidine derivatives, Alcohol and alcoholism, 29, 649-657.
[42] Lucas, J. H., Wheeler, D. G., Emery, D. G. and Mallery, S. R. (1998). The
endogenous antioxidant glutathione as a factor in the survival of physically injured
mammalian spinal cord neurons, Journal of Neuropathology & Experimental
Neurology, 57, 10, 937-954.
[43] Grzybowski, A. E. (1999). In vitro effect of glutathione precursors on cytotoxicity
of amino acids to human mesothelial cells, Journal of Physiology and
Pharmacology, 50, 3, 463-475.
[44] Guayerbas, N., Puerto, M., Ferrandez, M. D. and Fuente, M. D. L. (2002). A diet
supplemented with thiolic anti-oxidants improves leucocyte function in two strains
of prematurely ageing mice, Clinical and Experimental Pharmacology and
Physiology, 29, 11, 1009-1014.
[45] Yang, Y., Liu, W. S., Han, B. Q. and Sun, H. Z.(2006). Antioxidative properties of
a newly synthesized 2-glucosamine-thiazolidine-4(R)-carboxylic acid
(GlcNH2Cys) in mice, Nutrition Research, 26, 7, 369-377.
[46] Arora, K., Jose, D., Singh, D., Gupta, R. S., Pardasani, P. and Pardasani, R. T.
(2010). Stereoselective synthesis and antioxidant activity of azabicycloadducts
derived from 9,10-phenanthrenequinone, Heteroatom Chemistry, 20, 7, 379-392.
[47] Vavrova, A., Popelova, O., Sterba, M., Jirkovsky, E., Haskova, P., Mertlikova Kaiserova, H., Gersl, V. and Simunek, T. (2011). In vivo and in vitro assessment of
the role of glutathione antioxidant system in anthracycline-induced cardiotoxicity,
Archives of Toxicology, 85, 525-535.
[48] Saltman, A. E. (2015). D-ribose-L-cysteine supplementation enhances wound
healing in a rodent model, The American Journal of Surgery, 210, 153-158
[49] Onen Bayram, F. E., Sipahi, H., Acar, E. T., Kahveci, U. R., Buran, K. and Akgun,
H. (2016). The cysteine releasing pattern of some antioxidant thiazolidine-4-
carboxylic acids, European Journal of Medicinal Chemistry, 114, 337-344.
[50] Jagtap, R. M. and Pardeshi, S. K. (2014). Antioxidant activity screening of a series
of synthesized 2-aryl thiazolidine-4-carboxylic acids, Der Pharmacia Lettre, 6, 3,
137-145.
[51] Pardasani, R. T., Pardasani, P., Muktawat, S., Chaturvedi, V. and Mukherjee, T.
(1998). Reaction of 2-thiazoline-2-thiol with isatin derivatives, Phosphorus, Sulfur
and Silicon and the Related Elements, 142, 221-227.
[52] El-Sharkawy, K. A. (2011). Synthesis and antimicrobial activity of 2-substituted-3-
acetyl-thiazolidine-4-carbonyl-amino acid derivatives, International Journal of
Pharmaceutical Sciences, 3, 1005-1014.
[53] Bhat, M. A., Siddiqui, N., Khan, S. A. and Mohamed, I. (2009). Synthesis of triazole
thiazolidinone derivatives of coumarin with antimicrobial activity, Acta Poloniae
Pharmaceutica, 66, 625-632.
[54] Gupta, M., Minu, M. and Pathak, D. (2012). Synthesis and antimicrobial activity of
some substituted novel thiazolidine-4-one derivatives, Journal of Pharmaceutical
Research, 11, 25-28.
[55] Naik, M. M., Bhangui, P. and Bhat, C. (2017). The first report on Listeria
monocytogenes producing siderophores and responds positively to N-acyl
homoserine lactone (AHL) molecules by enhanced biofilm formation, Archives of
Microbiology, 199, 1409-1415.