- STEREOSPECIFICITY IN THE PICTET-SPENGLER REACTION. ENANTIOSPECIFIC SYNTHESIS OF (6S,10S)-(-)-5-METHYL-9-OXO-12-BENZYL-6,7,8,9,10,11-HEXAHYDRO-6,10-IMINO-5H-CYCLOOCTINDOLE, A TEMPLATE FOR PREPARATION OF MACROLINE/SARPAGINE ALKALOIDS
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The synthesis of the tetracyclic ketone was carried out in enantiospecific fashion (>98percent ee) via the 1,3-transfer of chirality from Na-methyl, Nb-benzyl tryptophan methyl ester to the trans diastereomer in the Pictet-Spengler reaction.Although the condensation of 14 with aldehyde (15) in refluxing benzene generated the tetrahydro β-carbolines (4b/5b) in a kinetic ratio (72:28), epimerization (C-1) of the cis diastereomer into the trans isomer occurred stereospecifically under acidic conditions.Dieckmann cyclizatin of either the Na-methyl, Nb-benzyl-cis-(+)-5b or trans-(-)-4b diastereomer provided the cis-bicyclo-azanonane system at approximately the same rate, although the β-keto esters were antipodal, in contrast to results reported in the Na-benzyl series by Magnus.
- Zhang, Lin-Hua,Bi, Ying-Zhi,Yu, Fu-Xiang,Menzia, Gerald,Cook, James M.
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p. 517 - 547
(2007/10/02)
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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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