Oxaprotiline is a racemic compound composed of two isomers, R(−)- or levo- oxaprotiline (levoprotiline; CGP-12,103-A), and S(+)- or dextro- oxaprotiline (dextroprotiline; CGP-12,104-A). Both enantiomers are active, with the levo- form acting merely as an antihistamine and the dextro- form having a more expansive pharmacology (see below), but with both unexpectedly still retaining antidepressant effects.
The first few steps leading to the key intermediate (1) parallel those for maprotiline starting with an acetic rather than a propionic acid. The carboxyl group is reduced to an aldehyde by sequential conversion to its acid chloride and then hydrogenation over a poisoned palladium catalyst. Reaction of the aldehyde with hydrogen cyanide leads to the corresponding cyanohydrin, which now incorporates the required third side chain carbon. Reduction with LAH yields the aminoalcohol. The primary amino group can then be monomethylated by any of several methods such as conversion to its carbamate followed by a second hydride reduction.
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^Noguchi S, Fukuda Y, Inukai T (May 1992). "Possible contributory role of the central histaminergic system in the forced swimming model". Arzneimittel-Forschung42 (5): 611–3. PMID1530672.
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