Rh. Lin et al., ENANTIOSPECIFIC SYNTHESIS OF NATURAL (-)-COCAINE AND UNNATURAL (-COCAINE FROM D-GLUTAMIC AND L-GLUTAMIC ACID()), Journal of organic chemistry, 63(12), 1998, pp. 4069-4078
Natural (-)-cocaine and unnatural (+)-cocaine have been synthesized en
antiospecifically from D- and L-glutamic acid, respectively. The axial
-equatorial substitutents were introduced by a stereo- and regiospecif
ic dipolar cycloaddition to the corresponding (LR,5S)- and (1S,5R)-N-B
OC-nortropenes with (ethoxycarbonyl)formonitrile N-oxide. A sequence o
f subsequent stereochemically controlled transformations converted the
fused isoxazoline to the requisite P-hydroxy ester. Synthesis of the
key intermediate N-BOC-nortropenes involved construction of the 8-azab
icyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-subst
ituted D-and L-proline esters. For comparison, (1R,SS)-N-BOC-nortropen
e also was derived by degradation from natural cocaine. The cis-5-subs
tituted D-and L-proline esters were obtained by sulfide contraction an
d 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.