Michael addition of enolizable carbonyl compounds to nitroalkenes is a particularly appealing transformation, because it can serve in the synthesis of many bioactive molecules. One of them is pregabalin, a member of the gaba-pentinoid family of drugs used for the treatment of neuropathic pain and partial seizures. It is manufactured by a chemoenzymatic process. Organocatalytic approaches were also shown to be viable for pregabalin synthesis.
R. Baran, E. Veverková, A. Škvorcová, R. Šebesta, Org. Biomol. Chem. 2013, 11, 7705-7711.
Asymmetric dipolar cycloadditions as well as hetero-Diels-Alder reactions present an efficient method to synthesise heterocyclic products useful in pharmaceutical industry. Considerable disadvantage of organocatalytic dipolar cycloadditions is impractically long reaction times, which are necessary to obtain products in reasonable yields. Particularly, reactions of nitrones often last for several days. Use of ionic liquids, microwave and ultrasonic irradiation or other non-classical experimental techniques can have a positive impact on organocatalytic reactions.
M. Mojzesová, M. Mečiarová, A. Almássy, R. Marti, R. Šebesta, Chem. Pap.2015, 69, 737-746.
Oseltamivir phosphate is an active component of Tamiflu, one of the most potent antiviral drugs. It is currently produced via a 13 step synthesis. This synthesis suffer from potentially unreliable source of the starting material and involvement of hazardous procedures in the synthesis. Therefore, a great effort has been devoted to developing alternative syntheses. Use of asymmetric organocatalysis in the synthesis of oseltamivir has pioneered Hayashi and co-workers.
J. Rehák, M. Huťka, A. Latika, H. Brath, A. Almássy, V. Hajzer, J. Durmis, S. Toma, R. Šebesta, Synthesis 2012, 44, 2424-2430.
Chiral thioureas have found many applications as chiral catalysts. We have developed hydrogen bond-catalyzed aza-Mannich addition of azlactones (oxazol-5(4H)-ones) (1) to aldimines 2. The process benefits from the ability of bifunctional thioureas to affect the formation of α,β-diaminoacids precursors 3 in high yields and stereoselectivities. These compounds can be subsequently transformed into various α-substituted α,β-diaminoacids derivatives.
M. Žabka, A. Malastová, R. Šebesta RSC Adv.2015, 5, 12890-12893.