Synthesis of densely functionalized enantiopure indolizidines by ring-closing metathesis (RCM) of hydroxylamines from carbohydrate-derived nitrones.
BACKGROUND
Indolizidine alkaloids widely occur in nature and display interesting biological activity. This is the reason for which their total synthesis as well as the synthesis of non-natural analogues still attracts the attention of many research groups. To establish new straightforward accesses to these molecules is therefore highly desirable.


RESULTS
The ring closing metathesis (RCM) of enantiopure hydroxylamines bearing suitable unsaturated groups cleanly afforded piperidine derivatives in good yields. Further cyclization and deprotection of the hydroxy groups gave novel highly functionalized indolizidines. The synthesis of a pyrroloazepine analogue is also described.


CONCLUSIONS
We have developed a new straightforward methodology for the synthesis of densely functionalized indolizidines and pyrroloazepine analogues in 6 steps and 30-60% overall yields from enantiopure hydroxylamines obtained straightforwardly from carbohydrate-derived nitrones.
Bonanni
Marco
M
Dipartimento di Chimica Organica "Ugo Schiff", Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Biologicamente Attivi (HeteroBioLab), Università di Firenze, via della Lastruccia 13, I-50019 Sesto Fiorentino (Firenze), Italy. marco.bonanni@unifi.it
Marradi
Marco
M
Cardona
Francesca
F
Cicchi
Stefano
S
Goti
Andrea
A