9α- and 9β-hydroxyphenylmorphans

Article abstract of DOI:10.1002/jps.2600731261

Platinum-oxide hydrogenation of 5-m-methoxyphenyl-2-methyl-9-oxomorphan (I) gave the 9α-hydroxy racemate (II) whose phenolic analogue (III) is a strong antinociceptive agent, fully supportive of morphine dependence in rhesus monkeys. The di-O-acetyl derivative (VI) of III was similar to III in its profile of activity. The diastereoisomer of III (VII), obtained by hydrogenation of the methobromide of I (IV), extrusion of methyl bromide, and O-demethylation of the resultant free base (VIII), was almost inactive antinociceptively and did not suppress withdrawal symptoms in morphine-dependent monkeys. The orientation of the C-9 hydroxyl groups was deduced from spectral data and by analogy.