Asymmetric total synthesis of the 1-epi-aglycon of the cripowellins A and B.
[structure: see text] The unusual [5.3.2]-bicyclic structure of the insecticidal Amaryllidaceae alkaloids cripowellin A (1) and B (2) has been synthesized for the first time via a sequence of Sharpless dihydroxylation, ring-closing metathesis, and intramolecular Heck reaction. The asymmetric synthesis of the 1-epi-aglycon 82 proceeds with virtually complete diastereo- and enantioselectivity (de, ee > or = 98%) in 13 steps and an overall yield of 5.6%. In addition, three alternative approaches toward the aglycon 3 are also described focusing on (1) the alkylation of the 2-benzazepinedithianes 35 and 36 with the electrophile 11, (2) a radical cyclization of the precursor (R/S,S,S)-39, and (3) an intramolecular arylation reaction of the aryl ketone 47.
Enders
Dieter
D
Institut für Organische Chemie, RWTH Aachen, Landoltweg 1, 52074 Aachen, Germany. enders@rwth-aachen.de
Lenzen
Achim
A
Backes
Michael
M
Janeck
Carsten
C
Catlin
Kelly
K
Lannou
Marie-Isabelle
MI
Runsink
Jan
J
Raabe
Gerhard
G
D000470:Alkaloids / Q000138:chemical synthesis; D000478:Alkylation; D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis*; D003500:Cyclization; D013237:Stereoisomerism
D000470:Alkaloids; D047151:Amaryllidaceae Alkaloids; C506143:cripowellin A; C506144:cripowellin B