Total synthesis and pharmacological activities of N-substituted 3,14-dihydroxymorphinans. I

Butorphanol: Effects of a Prototypical Agonist-Antagonist Analgesic on κ-Opioid Receptors

“…Synthesis of butorphanol was first reported in 1973 as a product of a program directed towards creation of narcotic antagonists in which potent clinical analgesic activity could be found at doses that did not elicit significant psychotomimetic effects (1). At normal therapeutic doses, butorphanol was concluded to possess analgesic activity with an abuse potential and dependence liability lower than that exhibited by morphine (2,3).…”

Synthetic Morphinans and Hasubanans. II. On the Mechanism of Acid-catalyzed Transformations of 17-(N-Phenylthioamido)-3-methoxy-Δ8,14-morphinan

“…This was reduced with lithium aluminum hydride to the 10P-thiohasubanan 7, which in turn was hydrogenolized with Raney nickel to afford 8. The reaction of 8 with methyl iodide gave quaternary salt 9 and treatment of this with potassium hydroxide in boiling 1-butanol (Hofmann elimination conditions) afforded aminohexahydrophenanthrene 10, which was identical to the sample obtained by reductive methylation (Raney Ni, H,, CH,O) of the aminohexahydrophenanthrene 11 (1 For personal use only.…”

“…The reaction of 3-methoxy-~~~'~-morphinan (1) with phenyl isothiocyanate afforded the starting material, thioamidomorphinan 1. Treatment of 1 with concentrated sulfuric acid a t room temperature afforded a mixture of thioureidohasubanan 2 (68%) and thiazinohasubanan 3 (8'3).…”

The Synthesis of 4a-Aminoalkyl-1,2,3,4,4a,9-Hexahydrophenanthrenes. Versatile Intermediates for Potential CNS Drugs. I

“…Later Generally speaking, 2,2-tetramethylene-]-tetra-Papers will describe the cyclization a n d related lone 2 (R' = H or 0 C H 3 ) can react with chemistry of some of these 4-type systems (10). Reformatsky (I), Grignard (I), Wittig or Carey's A ~0mmunication concerning the application of reagents to give adducts that are especially prone the above described approach has been published to suffer Wagner-Meerwein arrangements so as recently (9). to yield 4a-substituted-1,2,3,4,4a,9-hexahydrophenanthrenes (4) and/or the isomeric 2,3,4,4a,-…”