Enantioselective total syntheses of the Ipecacuanha alkaloid emetine, the Alangium alkaloid tubulosine and a novel benzoquinolizidine alkaloid by using a domino process.
The first enantioselective syntheses of the Ipecacuanha alkaloid emetine (1) and the Alangium alkaloid tubulosine (2) is described employing a domino Knoevenagel/hetero-Diels-Alder reaction and an enantioselective catalytic transfer hydrogenation of imines as key steps. Thus, hydrogenation of the imine 15 with the catalyst (R,R)-16 gives the tetrahydroisoquinoline 14 with 95 % ee which was transformed into the aldehyde (1S)-7. The three-component domino reaction of (1S)-7 with 6 and 8 led to 19, which in a second domino process was treated with K(2)CO(3) in methanol followed by a hydrogenation to give the benzoquinolizidine 4 together with the diastereomers 22 and 23 in a overall yield of 66 %. Further transformation of 4 with the amines 3 and 5 yielded enantiopure emetine (1) and tubulosine (2), respectively. In addition, starting from 19 the novel benzoquinolizidine alkaloid 34 was synthesised; this compound resembles the vallesiachotamine alkaloid dihydroantirhin 31, which has not been isolated so far but probably must also exist in nature.
Tietze
Lutz F
LF
Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany. ltietze@gwdg.de
Rackelmann
Nils
N
Müller
I
I
D032604:Alangiaceae / Q000737:chemistry*; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D004640:Emetine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D007486:Ipecac / Q000737:chemistry*; D008968:Molecular Conformation
D000470:Alkaloids; D006575:Heterocyclic Compounds, 3-Ring; C009805:tubulosine; D007486:Ipecac; D004640:Emetine