Various Applications of Functionalized Tetrazoles in Medicinal and Materials Chemistry

Although the tetrazole fragment has not been found in natural sources, it has attracted much attention because of a broad spectrum of biological activities and unique material properties exhibited by numerous tetrazole derivatives [1-2]. Substituted tetrazoles are heavily used in medicinal chemistry as metabolically stable isosteres of carboxylic acids [3], surrogates of cis-amide bonds [2], and potential anticancer agents [4]. Their applications also include the synthesis of modified amino acids [5], and peptidomimetics [6]. Today, the tetrazole moiety is found to be present in 22 marketed drugs demonstrating distinctly different mechanisms of action, e.g., antibacterial Cefotiam 1 and antihypertensive Losartan 2 (Fig. 1) [7].

Besides medicinal applications, some tetrazoles are used in agriculture as plant growth regulators and in the food industry as sweeteners [8]. The synthetic utility of functionalized tetrazoles was nicely demonstrated by E-selective olefination of aldehydes with alkyl tetrazolyl sulfones [9] and asymmetric addition to olefins catalyzed by chiral tetrazoles, such as 3 (Fig. 1) [10]. The excellent ability of tetrazole nitrogen atoms to coordinate metal ions led to the development of many tetrazole-based ligands for constructing functional metal-organic complexes (e.g., metal-organic frameworks for gas storage purposes [11]). Noteworthy, synthetic polymers having tetrazole fragments in their repeating units are considered highly prospective materials [12]. For example, polymer 4, prepared as a microporous organic material, was shown to capture CO₂ gas with high efficacy and selectivity [13]. 

Figure 1. Examples of tetrazole-derived drugs and materials.

Illustrated below is our proprietary collection of functionalized tetrazoles to become promising reagents for the synthesis of new bioactive or functional compounds.

The complete list of the related structures can be obtained upon request.

Please, contact us at marketing@lifechemicals.com for any additional information and price quotations.

References

1. Arulmozhi, R.; Abirami, N.; Helen, K. P. Int. J. Pharm. Sci. Rev. Res. 2017, 46, 110-114.
2. (a) Mittal, R.; Awasthi, S. K. Synthesis 2019, DOI:10.1055/s-0037-1611863. (b) Ostrovskii, V.A.; Koldobskii, G.I.; Trifonov, R.E. in Comprehensive Heterocyclic Chemistry, 3rd edition, eds. A.R. Katritzky, C.A. Ramsden, E.F.V. Scriven, and R. J.K. Taylor Pergamon, Oxford, 2008. Vol. 6, p. 257.
3. Herr, R.J. Bioorg. Med. Chem. 2002, 10, 3379.
4. Zhang, J.; Wang, S.; Ba, Y.; Xu, Z. Eur. J. Med. Chem. 2019, 178, 341-351.
5. Demko, Z.P.; Sharpless, K.B. Org. Lett. 2002, 4, 2525.
6. Lodyga-Chruscinska, E.; Brzezinska-Blaszczyk, E.; Micera, G.; Sanna, D.; Kozlowski, H.; Olczak, J.; Zabrocki, A.K. J. Inorg. Biochem. 2000, 78, 283.
7. www.drugbank.ca; accessed on August 2019.
8. Butler, N.R. in Comprehensive Heterocyclic Chemistry, 2nd edition, eds. R. Katritzky, C. W. Rees, and E.F.V. Scriven Pergamon, Oxford, 1996. Vol. 4, p. 621.
9. Lebrun, M.-E.; Le Marquand, P.; Berthelette, C. J. Org. Chem. 2006, 71, 2009 and references therein.
10. Prieto, A.; Halland, N.; Jørgensen, K.A. Org. Lett. 2005, 7, 3897.
11. Cui, P.; Ma, Y.-G.; Li, H.-H.; Zhao, B.; Li, J.-R.; Cheng, P.; Balbuena, P.B.; Zhou, H.C. J. Am. Chem. Soc., 2012, 134, 18892.
12. Kizhnyaev, V.N.; Vereshchagin, L.I. Russ. Chem. Rev. 2003, 72, 143.
13. Du, N.; Park, H.B.; Robertson, G.P.; Dal-Cin, M.M.; Visser, T.; Scoles, L.; Guiver, M.D. Nat. Mat. 2011, 10, 372.