2003年12月
A synthesis of chiral 1,1,3-trisubstituted 1,2,3,4-tetrahydro-beta-carbolines by the Pictet-Spengler reaction of tryptophan and ketones: Conversion of (1R,3S)-diastereomers into their (1S,3S)-counterparts by scission of the C(1)-N(2) bond
CHEMICAL & PHARMACEUTICAL BULLETIN
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- 巻
- 51
- 号
- 12
- 開始ページ
- 1368
- 終了ページ
- 1373
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- 出版者・発行元
- PHARMACEUTICAL SOC JAPAN
The Pictet-Spengler cyclization of the imines (3) prepared by the condensation of L-tryptophan methyl ester (1) and aryl methyl ketones (2), using titanium(IV) isopropoxide as an iminating reagent, quantitatively proceeded, when treated with trifluoroacetic acid (TFA) or formic acid, to provide two diastereomers, that is (1S,3S)-1-aryl-3-isopropoxycarbonyl-1-methyl-1,2,3,4-tetrahydro-beta-carbolines (4) and their (1R,3S)-diastereomers (5), of which the diastereomer ratios varied from 1 to 5 depending on the reaction conditions. The (1R,3S)-diastereomers (5) are thermodynamically more stable than their (1S,3S)-congeners (4), as shown by equilibration experiments in TFA. The conversion of 4 to 5 (also 5 to 4) should occur under acidic conditions by cleavage of the C(1)-N(2) bond with complete retention of configuration at the C-3 chiral center. The low diastereo-selectivity observed in the Pictet-Spengler reaction of 1 and 2 is concluded to be a stereochemical outcome under conditions of kinetic control (lower temperature, shorter reaction time), while the high diastereo selectivity with preferential formation of the more stable isomer (5) is the result of thermodynamically controlled experiments (higher temperature, longer reaction time).
- リンク情報
- ID情報
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- ISSN : 0009-2363
- Web of Science ID : WOS:000187001900004