- Asymmetric Total Synthesis of Sarpagine-Related Indole Alkaloids Hydroxygardnerine, Hydroxygardnutine, Gardnerine, (E)-16-epi-Normacusine B, and Koumine
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Sarpagine-related indole alkaloids (-)-hydroxygardnerine, (+)-hydroxygardnutine, (-)-gardnerine, (+)-(E)-16-epi-normacusine B, and (-)-koumine were divergently synthesized via a common intermediate possessing a piperidine ring with an exocyclic (E)-ethylidene side chain, which was constructed by a gold(I)-catalyzed 6-exo-dig cyclization strategy.
- Kitajima, Mariko,Watanabe, Keisuke,Maeda, Hiroyuki,Kogure, Noriyuki,Takayama, Hiromitsu
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supporting information
p. 1912 - 1915
(2016/05/19)
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- Studies on Gelsemium alkaloids. Total synthesis of (+)-koumine, (+)-taberpsychine, and (+)-koumidine
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The total synthesis of the Gelsemium alkaloids (+)-koumine (2), (+)-taberpsychine (4), and (+)-koumidine (50) has been accomplished starting from (S)-(-)-tryptophan (21), All the synthetic alkaloids are antipodal to the natural compounds. N′ -Benzyltryptophan ((-)-22) was methylated to give 23 which was reductively benzylated to provide (-)-25. Pictet-Spengler condensation of (-)-25 with 2-ketoglutaric acid followed by esterification gave a mixture of diastereomeric methyl esters 27/28. Exposure of (+)-27 and (-)-28 to Dieckmann cyclization conditions provided (+)-29 and (-)-29, respectively. Thus starting from a single enantiomer of tryptophan both antipodes of the tetracyclic β-ketoesters (+)-29/(-)-29 are available. Since (+)-29 was the more readily available antipode, subsequent reactions were conducted with this compound. Conversion of (+)-29 into (+)-31 followed conventional lines. N-Alkylation of (+)-31 with propargyl bromide gave (+)-33 which was converted into (+)-36 by treatment with t-BuMe2SiOTf/Et3N, n-BuLi/CICO2Me, and LiBF4. Exposure of (+)-36 to pyrrolidine/ trifluoroacetic acid gave the (Z)- and (E)-quinuclidines (+)-37 and (+)-38. Methylenation of 38 with Tebbe's reagent gave 39. Both E and Z isomers were taken through the series of transformations to give 43, 45, 47, and 49 and 44, 46, 48, and 50. The structures of (+)-37 and (+)-43 were conclusively established by single-crystal X-ray crystallography. Fragmentation of 49 with methyl chloroformate gave 51 which was reduced with LiAlH4 to give (+)-taberpsychine (4). Treatment of 47 with methyl chloroformate gave the 18-hydroxytaberpsychine derivative 52 which was reduced with LiAlH4 to give 53. Similarly 48 gave 55. When the Z isomer 55 was exposed to the Mitsunubo conditions, (+)-koumine (2) was formed (40%, 72% based upon recovered 55). The E isomer 53 gave (+)-koumine (2) in lower yields at a much reduced rate.
- Magnus, Philip,Mugrage, Benjamin,DeLuca, Mark R.,Cain, Gary A.
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p. 5220 - 5230
(2007/10/02)
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- BIOMIMETIC SYNTHESIS OF KOUMINE BY THE PALLADIUM-CATALYZED INTRAMOLECULAR COUPLING REACTION OF 18-HYDROXYTABERPSYCHINE (18-HYDROXYANHYDROVOBASINEDIOL)
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A principal Gelsemium alkaloid, koumine (1) was synthesized from 18-hydroxygardnutine (3) via the demethoxylation from the indole ring and the palladium-catalyzed cyclization between C7 and C20 of the hypothetical biogenetic intermediate, 18-hydroxytaberpsychine (2).
- Takayama, Hiromitsu,Kitajima, Mariko,Sakai, Shin-ichiro
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p. 325 - 327
(2007/10/02)
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