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Enantioselective Total Syntheses of the Ipecacuanha Alkaloid Emetine, the Alangium Alkaloid Tubulosine and a Novel Benzoquinolizidine Alkaloid by Using a Domino Process
Author(s) -
Tietze Lutz F.,
Rackelmann Nils,
Müller I.
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200306039
Subject(s) - enantioselective synthesis , alkaloid , chemistry , tetrahydroisoquinoline , emetine , domino , stereochemistry , organic chemistry , catalysis , biology , pharmacology
Abstract 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 (1 S )‐ 7 . The three‐component domino reaction of (1 S )‐ 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.