Asymmetric synthesis of the optically active piperidine alkaloid (+)-β-conhydrine

Lebrun, Stéphane; Couture, Axel; Deniau, Éric; Grandclaudon, Pierre

doi:10.1016/j.tetasy.2008.04.021

Cited by 24 publications

(4 citation statements)

References 38 publications

(13 reference statements)

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“…The diastereomers were separated by column chromoatography and hydrolysis of the major diastereomer gave the alkaloid (+)‐β‐conhydrine (er 84:16; NMR spectroscopic data matched the literature for this diastereomer). 17 The specific rotation, [ α ]${{{22\hfill \atop {\rm D}\hfill}}}$ = +6.0 (1.0, EtOH) was in line with that expected based on the literature value for enantiopure β‐conhydrine, [ α ]${{{20\hfill \atop {\rm D}\hfill}}}$ = +8.3 (0.9, EtOH) 17c. This two‐step procedure (overall yield from 16 , 48 %) represents a remarkably rapid access to this alkaloid.…”

Section: Resultssupporting

confidence: 70%

²H NMR Studies on Two‐Homopolypeptide Lyotropic Enantiodiscriminating Mesophases: Experimental Quantification of Solute–Fiber Affinities

Lesot

Lafon

Aroulanda

et al. 2008

Chemistry A European J

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The analytical potential and enantioselective properties of lyotropic mesophases made by mixing two chemically different chiral polypeptides are described. Here we examine the case of a mixture of poly-gamma-benzyl-L-glutamate (PBLG) and poly-epsilon-carbobenzyloxy-L-lysine (PCBLL). We demonstrate that 2H NMR spectroscopy on these chiral oriented mixtures can discriminate both enantiomers and enantiotopic directions in prochiral molecules. Moreover, in such systems, degree of enantiodiscrimination, resolution, and sensitivity can be conjointly optimized by changing the relative proportion of the two polypeptides. Therefore, these new enantiodiscriminating media provide a favorable alternative to single-polypeptide mesophases with respect to stereochemical applications. At a more fundamental level, the present work points out that solute distribution in the vicinity of each polypeptide partly governs the degree of enantiodiscrimination and NMR relaxation rates. To this end, the experimental trends of solute NMR observables (Delta nu Q, T1) versus the fraction of peptide units of each polymer were analyzed by using a "mean-field" model derived from that proposed for mixtures of thermotropic nematic solvents, and based on the separation of intermolecular interactions between the solute and both polypeptides. This approach allows the relative solute-fiber affinities in these lyotropic systems to be determined. To identify the factors controlling solute-polypeptide affinities, we investigated various solutes (polar/apolar, rigid/flexible, achiral/prochiral/chiral molecules) using 2H NMR at natural abundance or on isotopically enriched solutes.

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Section: Resultssupporting

confidence: 70%

²H NMR Studies on Two‐Homopolypeptide Lyotropic Enantiodiscriminating Mesophases: Experimental Quantification of Solute–Fiber Affinities

Lesot

Lafon

Aroulanda

et al. 2008

Chemistry A European J

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“…The structure of the LiAlH 4 reduction product was confirmed by comparing the recorded NMR ( 1 H-and 13 C-) spectral and specific rotation data (observed: +7.1 in EtOH, reported +7.9 in EtOH) with the data available in the literature. 28 We also synthesized (+)-β-conhydrine analogues 26b, 26c and 8c (R = Bu, t Bu and Ph) following the epoxide opening followed by lactam reduction strategy (Table 1, entries 6-8) in 21-28% yields.…”

Section: Resultsmentioning

confidence: 99%

Diastereoselective construction of syn-α-oxyamines via three-component α-oxyaldehyde–dibenzylamine–alkyne coupling reaction: application in the synthesis of (+)-β-conhydrine and its analogues

2012

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A Cu(I)-catalyzed α-oxyaldehyde-dibenzylamine-alkyne coupling reaction was delineated for the construction of α-oxyamines with excellent yields and diastereoselectivity. Crystal structure analysis and theoretical calculations were also supportive of the formation of syn-α-oxyamines as the major products. Application of the methodology addresses the synthesis of (+)-β-conhydrine along with analogs having two different diversity features. A ring size variation allows construction of piperidine and pyrrolidine rings while a variation of side arm functionality is achieved by complete regioselective opening of epoxide by different organocopper ylides (Gilman reagents). A lactam-Cu(I) complexation motif is proposed which allows an intramolecular attack of ylides at the terminal epoxy carbon via the six-membered cyclic transition state. The present work features the synthesis of (+)-β-conhydrine over eight steps in 26% yield and its seven analogs in 21-28% yields.

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“…An ingenious approach to the construction of chiral benzazepine derivatives and cyclic alkaloid skeletons was realized by the combination of a diastereoselective 1,2-addition and the ring-closing metathesis reaction. For example, the highly stereoselective 1,2-addition to benzyl-protected 4-hydroxybutyraldehyde or 5-hydroxypentanal SAMP-hydrazones (Scheme ), combined in a one-pot reaction of the directly resulting lithium hydrazide with acryloyl chloride, gave hydrazine derivatives 204 .…”

Section: Nucleophilic Additions To Nn-dialkylhydrazonesmentioning

confidence: 99%

N,N-Dialkylhydrazones in Organic Synthesis. From Simple N,N-Dimethylhydrazones to Supported Chiral Auxiliaries

2009

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Asymmetric synthesis of the optically active piperidine alkaloid (+)-β-conhydrine

Cited by 24 publications

References 38 publications

²H NMR Studies on Two‐Homopolypeptide Lyotropic Enantiodiscriminating Mesophases: Experimental Quantification of Solute–Fiber Affinities

²H NMR Studies on Two‐Homopolypeptide Lyotropic Enantiodiscriminating Mesophases: Experimental Quantification of Solute–Fiber Affinities

Diastereoselective construction of syn-α-oxyamines via three-component α-oxyaldehyde–dibenzylamine–alkyne coupling reaction: application in the synthesis of (+)-β-conhydrine and its analogues

N,N-Dialkylhydrazones in Organic Synthesis. From Simple N,N-Dimethylhydrazones to Supported Chiral Auxiliaries

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Asymmetric synthesis of the optically active piperidine alkaloid (+)-β-conhydrine

Cited by 24 publications

References 38 publications

2H NMR Studies on Two‐Homopolypeptide Lyotropic Enantiodiscriminating Mesophases: Experimental Quantification of Solute–Fiber Affinities

2H NMR Studies on Two‐Homopolypeptide Lyotropic Enantiodiscriminating Mesophases: Experimental Quantification of Solute–Fiber Affinities

Diastereoselective construction of syn-α-oxyamines via three-component α-oxyaldehyde–dibenzylamine–alkyne coupling reaction: application in the synthesis of (+)-β-conhydrine and its analogues

N,N-Dialkylhydrazones in Organic Synthesis. From Simple N,N-Dimethylhydrazones to Supported Chiral Auxiliaries

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²H NMR Studies on Two‐Homopolypeptide Lyotropic Enantiodiscriminating Mesophases: Experimental Quantification of Solute–Fiber Affinities

²H NMR Studies on Two‐Homopolypeptide Lyotropic Enantiodiscriminating Mesophases: Experimental Quantification of Solute–Fiber Affinities