モルヒナン骨格の特異な反応とその骨格を利用した活性アルカロイドの合成

抄録

Morphinan alkaloids, such as morphine, codeine, heroin, and thebaine, which are called opioids, are pharmacologically important compounds and widely known to express a variety of pharmacological action by acting on µ, δ, and κ opioid receptors (MOR, DOR, and KOR). Naltrexone, which is one of the commercially available 4,5-epoxymorphinan alkaloids, is a drug mainly used to manage alcohol dependence and opioid dependence. From a viewpoint of pharmacology, naltrexone is categorized as a MOR antagonist. On the other hand, from a viewpoint of organic chemistry, it has a wealth of functional groups and four consecutive asymmetric centers in the single molecule, and thus, naltrexone or its derivatives show a characteristic of chemical reactivity. In this article, unique reactions of morphinan skeletons based on our recent research in medicinal chemistry were described. In the first chapter, we focused on the effects of the hydroxy group at the C14 position and the tetrahydrofuran-ring (4,5-epoxy-ring, E-ring) in the naltrexone derivatives to lead the abnormal reactions. In the second chapter, we described the synthetic transformations of naltrexone into (−)-galanthamine and (−)-homogalanthamine. This article would hopefully be useful information for both organic synthetic chemists and medicinal chemists.