Facile and enantiospecific syntheses of (6S,7R)-6-chloro-7-benzyloxy-, (7S)-halo-, and (7S)-hydroxy-cocaine and natural (-)-cocaine from D-(-)-ribose.

@article{Shing2011FacileAE,
  title={Facile and enantiospecific syntheses of (6S,7R)-6-chloro-7-benzyloxy-, (7S)-halo-, and (7S)-hydroxy-cocaine and natural (-)-cocaine from D-(-)-ribose.},
  author={Tony Kung Ming Shing and King Ho So},
  journal={Organic letters},
  year={2011},
  volume={13 11},
  pages={
          2916-9
        }
}
  • T. Shing, K. So
  • Published 5 May 2011
  • Chemistry, Biology
  • Organic letters
First syntheses of C6,7 and C7 enantiopure cocaine analogues were achieved from D-(-)-ribose via a trans-acetonide controlled endo-selective intramolecular nitrone-alkene cycloaddition (INAC) as the key step. This synthetic scheme allows practical preparation of cocaine analogues for bioevaluation as potential candidates for the treatment of cocaine addiction and as potential conjugates for immunotherapy. 
17 Citations
Enantioselective synthesis of cocaine C-1 analogues using sulfinimines (N-sulfinyl imines).
TLDR
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Copper(I)-catalyzed three component reaction of sulfonyl azide, alkyne, and nitrone cycloaddition/rearrangement cascades: a novel one-step synthesis of imidazolidin-4-ones.
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The work reveals that a chelate-type interaction in the transition state of a β-aminoalkyl radical in a copper(I)-catalyzed 5-exo-trig radical cyclization step changes the usual stereochemistry of
Desymmetrization of bicyclo[3.n.1]-3-one derivatives by palladium-catalyzed asymmetric allylic alkylation.
TLDR
Desymmetrization of carbon nucleophiles by palladium-catalyzed asymmetric allylic alkylation has been realized for the first time and offers an efficient access to optically active tropane derivatives.
Stereoselective Synthesis of Tropanes via a 6π‐Electrocyclic Ring‐Opening/ Huisgen [3+2]‐Cycloaddition Cascade of Monocyclopropanated Heterocycles
TLDR
The synthesis of tropanes via a microwave‐assisted, stereoselective 6π‐electrocyclic ring‐opening/ Huisgen [3+2]‐cycloaddition cascade of cyclopropanated pyrrole and furan derivatives with electron‐deficient dipolarophiles is demonstrated, being versatile building blocks for the synthesis of pharmaceutically relevant targets.
Economical Synthesis of 13C-Labeled Opiates, Cocaine Derivatives and Selected Urinary Metabolites by Derivatization of the Natural Products
TLDR
The synthetic work has focused on identifying 13C atom-efficient routes towards these derivatives, and the 13C-labeled opiates and cocaine derivatives were made from the corresponding natural products.
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References

SHOWING 1-10 OF 27 REFERENCES
Total synthesis of (+)-cocaine via desymmetrization of a meso-dialdehyde.
[reaction: see text] The total synthesis of (+)-cocaine is described. An extension of the recently reported proline catalyzed intramolecular enol-exo-aldol reaction to a meso-dialdehyde provided the
Asymmetric total synthesis of (S)-(+)-cocaine and the first synthesis of cocaine C-1 analogs from N-sulfinyl β-amino ester ketals.
Sulfinimine-derived α,β-unsaturated pyrrolidine nitrones, on heating with Al(O-t-Bu)(3), undergo a highly stereoselective intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines, which
trans-acetonide controlled endo-selective intramolecular nitrone-alkene cycloaddition of hept-6-enoses: a facile entry to calystegines, tropanes, and hydroxylated aminocycloheptanes.
High-yielding endo-selective intramolecular nitrone-alkene cycloaddition (INAC) reactions of hept-6-enoses controlled by a trans-acetonide to give bridged bicyclo[4.2.1]isoxazolidines exclusively are
Total synthesis of (-)-cocaine and (-)-ferruginine.
TLDR
This work developed a general and practical method for the preparation of enantiopure cis-2,5-disubstituted pyrrolidines bearing alkene- and/or alkyne-containing substituents and offered two highly efficient pathways for the conversion of the 3-bromo-2-isoxazoline ring into the desired cis- 2,3-disubsituted groups in (-)-cocaine and (-)-ferruginine.
Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from d- and l-Glutamic Acid
Natural (−)-cocaine and unnatural (+)-cocaine have been synthesized enantiospecifically from d- and l-glutamic acid, respectively. The axial−equatorial substitutents were introduced by a stereo- and
Stereo- and regioselectivity in an intramolecular nitrone-alkene cycloaddition of hept-6-enoses with a trans-acetonide blocking group.
From sugar to cycloadduct: The effect of the trans-acetonide blocking group and the stereochemistry of the substituents on the regio- and stereoselectivity in the intramolecular nitrone-alkene
Experimental and theoretical studies on stereo- and regioselectivity in intramolecular nitrone-alkene cycloaddition of hept-6-enoses derived from carbohydrates.
The effect of blocking groups and stereochemistry of the substituents on the regio- and stereoselectivity in intramolecular nitrone-alkene cycloaddition (INAC) of hept-6-enoses are reported.
Masked oxo sulfinimines (N-sulfinyl imines) in the asymmetric synthesis of proline and pipecolic acid derivatives.
TLDR
On addition of Et2AlCN/i-PrOH, masked oxo sulfinimines give alpha-amino nitriles that afford oxo alpha-AMino acids on hydrolysis that are reduced to cis proline and cis pipecolic acids derivatives in high ee and good yield.
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