- A Concise, Enantioselective Approach for the Synthesis of Yohimbine Alkaloids
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We report a concise, enantioselective synthesis of the yohimbine alkaloids (-)-rauwolscine and (-)-alloyohimbane. The key transformation involves a highly enantio- and diastereoselective NHC-catalyzed dimerization and an amidation/N-acyliminium ion cyclization sequence to furnish four of the five requisite rings and three of the five stereocenters in two operations. This route also provides efficient access to all four diastereomeric arrangements of the core stereotriad of the yohimbine alkaloids from a common intermediate. This platform approach in combination with the ability to access both enantiomers from the carbene-catalyzed reaction is a powerful strategy that can produce a wide range of complex alkaloids and related structures for future biomedical investigations.
- Miller, Eric R.,Hovey, M. Todd,Scheidt, Karl A.
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p. 2187 - 2192
(2020/02/04)
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- Enantiospecific synthesis of (-)-3-iso-19,20-dehydro-β-yohimbine from secologanin: A route to normal and pseudo stereoisomers of yohimbine
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Hydrolysis of secologanin ethylene acetal at pH 7 resulted in stereoselective aldol cyclisation to a cyclohexene aldehyde, which, on reductive amination and cyclisation with tryptamine afforded (-)-3-iso-19,20- dehydro-β-yohimbine, converted into various normal and pseudo isomers of yohimbine. (C) 2000 Elsevier Science Ltd.
- Brown, Richard T.,Pratt, Simon B.,Richards, Paul
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p. 5627 - 5630
(2007/10/03)
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- Symmetry-driven synthesis of indole alkaloids: Asymmetric total synthesis of (+)-yohimbine, (-)-yohimbone, (-)-yohimbane, and (+)-alloyohimbane
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Total asymmetric syntheses of the target alkaloids are reported. The syntheses involve the preparation of enantiomerically pure (S,S)-1,3,3a,4,7,7a-hexahydro-2(H)-inden-2-one 7 and its meso isomer 5. Each ketone is then converted into a ring-expanded lactam using an oxaziridine synthesis/rearrangement protocol. The applications of Bischler-Napieralski ring constructions along with appropriate functional group transformations afford enantiomerically enriched alloyohimbane or yohimbane from the meso-or C2-symmetric ketones, respectively. A cis-5,6-diacetoxy compound (18) derived from the (S,S)-ketone served as the starting material for the total syntheses of the more highly functionalized alkaloids. Accordingly, a site-specific insertion of the indole-containing side chain was accomplished via stereoselective formation of an oxaziridine followed by its stereospecific rearrangement. The selectivity of this sequence allowed for the differentiation of alcohols at C-17 and C-18 (yohimbine numbering) and the synthesis of Δ18,19-yohimbone. This α,β-unsaturated ketone was converted into either (-)-yohimbone or (+)-yohimbine using standard chemistry.
- Aube,Ghosh,Tanol
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p. 9009 - 9018
(2007/10/02)
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- Total Syntheses of Yohimbe Alkaloids, with Stereoselection for the Normal, Allo, and 3-Epiallo Series, Based on Annelations of 4-Methoxy-1,2-dihydropyridones
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N--2,3-dihydro-4-pyridone (31) was generated in two steps (77percent yield) from tryptamine and N-methyl-4-piperidone methiodide.Its cyclization (90percent yield) and oxidation (91percent yield) provided the tetracyclic analogue 32.O-Methylation and Robinson-type annelation of these vinylogous lactams (the latter in form of its Na-carbamate) furnished the dienones 38 (64percent) and 43 (90percent).Further elaboration by cyclization and/or reduction reactions selectively provided the 15,16-didehydroyohimbinones 7 and 44.Their reductions then led to yohimbinone (52, 20percent overall yield from tryptamine), alloyohimbinone (11, 19percent overall yield), and 3-epi-alloyohimbinone (10, 23percent overall yield), which led to yohimbine (3), β-yohimbine (9), 3-epi-alloyohimbine (53), and 3-epi-17-epi-alloyohimbine (54).
- Kuehne, Martin E.,Muth, Randy S.
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p. 2701 - 2712
(2007/10/02)
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- Photocyclisation of Enamides. Part 27. Total Syntheses of(+/-)-Yohimbine, (+/-)-Alloyohimbine, and (+/-)-19,20-Didehydroyohimbines
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Total syntheses of five indole alkaloids, (+/-)-yohimbine (10), (+/-)-alloyohimbine (11), and three (+/-)-19,20-didehydroyohimbines (15a, b, and c) (for the first time) were completed from a single common key intermediate (4) via a route involving the ste
- Naito, Takeaki,Hirata, Yumico,Miyata, Okiko,Ninomiya, Ichiya
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p. 2219 - 2226
(2007/10/02)
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- INDOLE ALKALOID SYNTHESIS
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The lecture describes the total synthesis of pseudoyohimbine and an approach to the deserpidine group of indole alkaloids by way of the route of nucleophilic addition to a pyridinium salt followed by acid-induced ring closure.
- Wenkert, Ernest
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p. 325 - 329
(2007/10/02)
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