Functionalized (-)-Cytisine Derivatives for Medicinal Chemistry and Organic Synthesis

Naturally occurring alkaloid (-)-cytisine 1 is an efficient acetylcholine agonist possessing a strong affinity to nicotinic acetylcholine receptors (nAChRs) [1]. Owing to its biological activity (-)-cytisine has been used as an active ingredient of anti-smoking medications [2]. Various chemical modifications of (-)-cytisine were applied to obtain novel bicyclic compounds for rational drug discovery [3]. For example, N-alkylations [4], reductive aminations [5], nitrations, halogenations, alkylations, and arylations allowed to obtain numerous biologically active (-)-cytisine analogs[6]. In search for innovative antiviral drugs, many compounds in which (-)-cytisine is attached to natural chromone [7] or coumarin [8] derivatives were prepared by aminomethylation [9] or alkylation [10] reactions. Additionally, the Diels-Alder reaction of N-alkyl and N-acyl derivatives of (-)-cytisine with N-substituted maleimides gave rise to several biologically potentcompounds [11].

In the given context, Life Chemicals offers various derivatives of (-)-cytisine, including those involving chromone, coumarin, and other heterocyclic substructures. These species can be considered both as building blocks and compounds for biological screening.

Some representatives are listed below. The full list of the title compounds can be obtained upon request by emailing marketing@lifechemicals.com.

References:

1. (a) Blom, A. E. M.; Rego Campello, H.; Lester, H. A.; Gallagher, T.; Dougherty, D. A. J. Am. Chem. Soc. 2019, 141, 15840. (b) Butler, M. S.; Robertson, A. A. B.; Cooper, M. A. Nat. Prod. Rep. 2014, 31, 1612.
2. (a) Etter, J.-F. Arc. Intern. Med. 2006, 166, 1553. (b) West, R.; Zatonski, W.; Cedzynska, M.; Lewandowska, D.; Pazik, J.; Aveyard, P.; Stapleton, J. N. Engl. J. Med. 2011, 365, 1193.
3. Rouden, J.; Lasne, M.-C.; Blanchet, J.; Baudoux, J. Chem. Rev. 2013, 114, 712.
4. (a) Sakhautdinov, I. M.; Mukhamet'yanova, A. F.; Dosniyazova, A. G.; Vinogradova, V. I.; Lobov, A. N.; Yunusov, M. S. Chem. Nat. Comp. 2019, 55, 398. (b) Liu, C.; Watt, D. S.; Frasinyuk, M. S.; Sviripa, V. M.; Zhang, W.; Bondarenko, S. P. US 20180344862 A1, 2018.
5. Lator, A.; Gaillard, Q. G.; Merel, D. S.; Lohier, J.-F.; Gaillard, S.; Poater, A.; Renaud, J.-L. J. Org. Chem.2019, 84, 6813.
6. Gallagher, T. C.; Rego Campello, H. PCT Int. Appl. WO 2018033742 A2, 2018.
7. (a) Gaspar, A.; Matos, M. J.; Garrido, J.; Uriarte, E.; Borges, F. Chem. Rev. 2014, 114, 4960–4992. (b) Bondarenko, S. P.; Makarenko, O. G., Vinogradova, V. I. et al. Chem. Nat. Compd. 2020, 56, 1040–1043.
8. (a) Venugopala, K. N.; Rashmi, V.; Odhav, B. Biomed Res Int. 2013, 963248. (b) Pinto, D. C. G. A.; Silva, A. M. S. Curr. Top. Med. Chem. 2017, 17, 3190–3198.
9. M. S. Frasinyuk1 A. V. Turov, V. I. Vinogradova, and V. P. Khilya Chem. Nat. Comp. 2007, 43, 285.
10. Bondarenko, S. P.; Makarenko, O. G.; Vinogradova, V. I.; Frasinyuk, M. S. Chem. Nat. Comp. 2020, 56, 1040.
11. (a) Tsypysheva, I.; Koval’skaya, A.; Petrova, P.; Lobov, A.; Borisevich, S.; Tsypyshev, D.; Fedorova, V.; Gorbunova, E.; Galochkina, A.; Zarubaev, V. Tetrahedron 2019, 75, 2933. (b) Chuyko, A.; Dolgonos, G.; Shivanyuk, A.; Fetyukhin, V.; Lukin, O. Synthesis 2021, in press.