The Desoxymorphines¹

Opioids and Efflux Transporters. Part 2: P-Glycoprotein Substrate Activity of 3- and 6-Substituted Morphine Analogs

“…Compound 7 is approximately 10 times more potent than morphine in the tail flick (0.2 vs 1.92 mg/kg) and phenylquinone (0.03 vs 0.4 mg/kg) assays. These data confirm previous studies 30 that describe the high opioid potency of 6-desoxy derivatives of morphine.…”

DARK Classics in Chemical Neuroscience: Heroin and Desomorphine

“…In this study, besides desomorphine, the authors found four 4,5-epoxymorphinan derivatives related to desomorphine (Figure ): didehydrodesomorphine ( 30 or 36 ), methyldesomorphine ( 37 ), dihydromorphine-3,6-dideoxy ( 38 ), and morphinan-4,5-epoxy-3-ol ( 39 ). , The latter two derivatives were also detected in trace amount by Alves . It is worth mentioning that the structure of didehydrodesomorphine, which is not given in Savchuk’s work, could correspond to desoxymorphine-C ( 30 ) (previously described by Small , ) or to dehydrodesomorphine ( 36 ), subsequently proposed as a synthetic intermediate by Alves . The concentration of desomorphine in the urine samples varied from trace amounts to 70–80% .…”

“…Desomorphine (dihydrodesoxymorphine-D) is a synthetic morphine analog, first described in the US in 1933 by the American chemist Lyndon Frederick Small and patented one year later. − It was originally synthesized as a more powerful morphine derivative with fewer side effects and, most importantly, improved tolerance and addictive properties. However, expectations were not met, and its use was soon outlawed (1936) in the US .…”

“…The free base of the compound is scarcely soluble in water at room temperature (solubility of 1.425 mg/L). However, the salt forms of desomorphine are freely soluble in water. , The first synthesis of desomorphine was described by Lyndon Frederick Small in 1933 , and in a patent in 1934 . In his reports, Small describes four different methods to obtain desomorphine (Scheme ).…”

“…In his reports, Small describes four different methods to obtain desomorphine (Scheme ). These synthetic pathways obtained desomorphine through a common catalytic hydrogenation step starting from different precursors in each case: (A) by catalytic hydrogenation of the halogenocodides, followed by demethylation; (B) by catalytic hydrogenation of the halogenomorphides; (C) by catalytic hydrogenation of desoxymorphine-C ( 30 ); , (D) a slight modification of method C. , …”