Synthesis of oncinotin-11-one, a macrocyclic polyamine alkaloid from Oncinotis tenuiloba

Article abstract of DOI:10.1002/hlca.19960790511

This paper presents a short synthesis of oncinotin-11-one (11), a minor alkaloid of Oncinotis tenuiloba (Apocynaceae). Based on a disconnection approach, the spermidine portion of the key intermediate 6 was constructed consecutively by simple N-alkylations starting from ethyl piperidine-2-carboxylate (1). Treatment of 6 with in situ lithiated 2-[(10-bromodecyl)oxy]tetrahydropyran resulted in the formation of the keto moiety under simultanous deprotection of the lactam N-atom to give the amino ketone 7 in 71% yield. Cleavage of the tetrahydro-2H-pyran-2-yl (Thp) portion and Jones oxidation of the resulting alcohol 8 gave the amino acid 9 which was cyclized. Final N-debenzylation of 10 provided the natural alkaloid 11. Only two protective groups were needed in this synthesis. The reaction of N-alkyl-lactams with organometallic reagents is discussed.