The Addition of Organomagnesium Halides to Pseudocodeine Types. II. Preparation of Nuclear Alkylated Morphine Derivatives¹

Abstract

the presence of the enol ether group. When dihydrothebaine is extracted from a Soxhlet apparatus into boiling ethereal methylmagnesium iodide an addition compound slowly separates, and at the end of five days no more dihydrothebaine can be detected. The product consists principally of a

Kappa opioids and the modulation of pain

“…However, the holy grail of opioids, an analgesic as effective as morphine but without the side effects, has remained elusive (Corbett et al 2006). One early success was the identification of metopon as a compound that retained morphine-like analgesia but caused fewer undesirable side effects (Eddy 1948;Gruber et al 1950;Keats and Beecher 1952;Small et al 1936). These observations provided the initial "proof of principle" that permeates contemporary opioid research (Rice 2003).…”

Recent Developments in the Chemistry of Thebaine and its Transformation Products as Pharmacological Targets

“…Small and his co-workers in the 30's showed that the action of Grignard reagents on any of several 6,7 derivatives of the opium alkaloids led to abnormal products in which alkylation at two different positions had taken place and the oxide bridge had been opened [110][111][112].…”

(−)‐N‐[(Cyclopropyl) methyl]‐3,4‐dimethoxy‐5‐methylmorphinan‐6‐one, an opioid agonist with preference for kappa opioid receptors

“…-The essential intermediate, 5-methyldihydrothebainone (l), was synthesized by a route different from that described by Small et al [3][4] who prepared 1 either from 8,14-dihydrothebaine (2) or 8,14-dihydrocodeinone enol acetate (3) with a Grignard reaction.…”

“…Catalytical hydrogenation over Pd/C in diluted AcOH, which was carried out similarly to the hydrogenation thebaine --f dihydrothebainone [6] [7], afforded 1 in 68 % yield. This new synthesis of 5-methyldihydrothebainone (1) provides a route to this important intermediate which is much more efficient than the one developed by Small and coworkers [3][4]. 0 -Methylation of 1 was accomplished with phenyltrimethylammonium chloride using K,CO, instead of NaH [2] as base.…”