cis- and trans-4-Chloro-
and 4-bromo-L-prolines have been synthesized stereospecifically, the key step
being SN2 displacement of a free or substituted 4-hydroxyl group in
suitably protected 4-hydroxy-L- prolines. Similar displacements with azide ion
followed by reduction provide convenient routes to cis- and trans-
4-amino-L-proline. A less satisfactory pathway to cis-4-aminoproline is
reduction of a 4- oximinoproline derivative. In the course of the syntheses,
which involve a variety of protecting groups, 45 new L-proline derivatives have
been prepared. Unexpected side reactions were the formation of cis-4-hydroxyprolinamide by the action of ammonia on trans-4- bromoproline,
and the reduction by sodium borohydride of N- benzyloxycarbonyl-4-oximinoproline
methyl ester to N-benzyloxycar- bonyl-4-oximinoprolinol.
The interaction of OsO4 and protected derivatives of
3,4-dehydro-DL-proline gives high yields of 2,3-trans-3,4-cis-3,4-dihydroxy-DL-proline derivatives, with only traces of the
2,3-cis-3,4-cis diastereoisomers. Corresponding α-glycolation with KMnO4
gives mixtures of the 2,3-trans-3,4-cis and 2,3-cis-3,4-cis isomers in the ratio 1 : 1. Separation of the components of
such mixtures is extremely difficult. The free amino acids in
these two families of the 3,4-dihydroxy-DL-prolines
have been characterized. Epimerization at C2 of 2,3-cis derivatives occurs readily. O-Tosylation
of the 2,3-cis series occurs more
readily than for other hydroxyprolines. Esters of N,O,O-tritosyl-2,3-trans-3,4-cis-3,4-dihydroxyproline are converted very rapidly by mild
alkali into the equivalent esters of X-tosylpyrrole-2-carboxylic
acid. For the corresponding N,O,O-tritosyl carboxylic
acid, decarboxylation also takes place during aromatization, to yield N-tosylpyrrole.
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