Thionation of quinolizidine alkaloids and their derivatives via Lawesson’s reagent

Abstract

Direct thionation of quinolizidine alkaloids (-)-cytisine, methylcytisine, thermopsine and some of their carbonyl derivatives was realized. It was established that carrying out of the reaction in the boiling toluene with 0.5 eq. of Lawesson’s reagent (LR) is most effective for synthesis of thio analogues of methyl-, allyl-, benzylcytisine and thermopsine. It was found, that formation of thioamides is preferable in the case with starting 3-carboxamides of (-)-cytisine or 2-oxo and 4-oxo derivatives of methylcytisine; and an excess of LR is needed for their exhaustive thionation. It was shown, that thionation of ‘cytisine substituted’ urea and thiourea, as well as Diels-Alder adducts of methylcitisine with phenylmaleimide on basis of this approach was not quite successful: only thionation of the 2-pyridone core has occurred. It should be noted that transformation of urea and thiourea is complicated by side reactions leading to low yields of thio products, and the result of LR interaction with mentioned above diastereomeric Diels-Alder adducts depends on their stereochemistry and thermodynamic stability under reaction conditions.

Graphical Abstract

Keywords:

• Thionation reaction
• Lawesson’s reagent
• quinolizidine alkaloids
• (-)-cytisine
• methylcytisine
• thermopsine

Disclosure statement

The authors reported no potential conflict of interest.

Additional information

Funding

This study is supported by Ministry of Science and Higher Education of the Russian Federation, state assignments No AAAA-A17-117011910025-6 (IT, AK, DT), No AAAA-A17–117011910027–0 (AL) and RFBR No 18-53-52004 (PP). All experiments were carried out using the equipment of Collective Use Service Centre ‘Chemistry’ of Ufa Institute of Chemistry UFRС RAS.