Use of chiral-pool approach into epi-thieno analogues of the scarce bioactive phenanthroquinolizidine alkaloids

Peter Šafář (1) , Štefan Marchalín (1) , Nadežda Prónayová (1) , Viktor Vrábel (1) , Ata Martin Lawson (2) , Mohamed Othman (2) , Adam Daïch (2, 3)

1 STU - Slovak University of Technology in Bratislava
2 URCOM - Unité de Recherche en Chimie Organique et Macromoléculaire
3 INC3M - Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire

The stereoselective synthesis of epi-thieno analogues of the phenanthroquinolizidine bioactive alkaloids (-)-Cryptopleurine and (-)-(15R)-Hydroxycryptopleurine was achieved in five steps starting from easily available enantiopure (S)-2-aminoadipic acid used as chiral pool and nitrogen atom source. During these investigations, both π-cationic cyclization of chiral N-thienylmethyl-6-oxopipecolinic acids into pure (S)-keto-lactams and theirs regioselective and diastereoselective reduction, considered as key steps of this sequence, were studied. Of particular interest, the Friedel-Crafts cyclization using (CF3CO)2O/BF3·Et2O show that near the expected keto-lactams, enamides and enamidones containing trifluoromethyl residue were isolated. A mechanism leading to the latter products with high synthetic potential was discussed. © 2016 Published by Elsevier Ltd.

Mots clés: 6-Oxopipecolinic acid; Diastereoselective reduction; Phenanthroquinolizidine alkaloids; Thienoquinolizidine; π-Cationic cyclization

Domaines: Chimie

Peter Šafář, Štefan Marchalín, Nadežda Prónayová, Viktor Vrábel, Ata Martin Lawson, et al.. Use of chiral-pool approach into epi-thieno analogues of the scarce bioactive phenanthroquinolizidine alkaloids. Tetrahedron, 2016, 72 (23), pp.3221-3231. ⟨10.1016/j.tet.2016.04.047⟩. ⟨hal-02413311⟩