1998/05/15 by Ronghui Lin, Josep Castells, Henry Rapoport · 3 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #Analytical Chemistry and Chromatography #Asymmetric Synthesis and Catalysis #Chemical Synthesis and Analysis
paper · doi:10.1021/jo980153t
openalex publication_date 1998/05/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/26
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 regiospecific dipolar cycloaddition to the corresponding (1 R,5 S )- and (1 S,5 R )- N -BOC-nortropenes with (ethoxycarbonyl)formonitrile N -oxide. A sequence of subsequent stereochemically controlled transformations converted the fused isoxazoline to the requisite β-hydroxy ester. Synthesis of the key intermediate N -BOC-nortropenes involved construction of the 8-azabicyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-substituted d - and l -proline esters. For comparison, (1 R,5 S )- N -BOC-nortropene also was derived by degradation from natural cocaine. The cis-5-substituted d - and l -proline esters were obtained by sulfide contraction and subsequent catalytic hydrogenation to induce stereospecifically the C-5 stereochemistry from d - and l -thiopyroglutamate, which in turn were prepared from d - and l -glutamic acids, respectively.