Method of making key intermediates useful in the synthesis of many opiate narcotics and antagonists and agonists; and the non-opiate enantiomers thereof which have potent antitussive properties.

A new synthetic process has been found in which nordihydrocodeinone, an early intermediate in the total synthesis of codeine and related compounds, is easily formed into a number of N-nor compounds. These N-nor compounds can be used as precursors in the formation of narcotics, narcotic antagonists, or narcotic agonist-antagonists.

 

The manufacture of drugs of this type, such as northebaine or normorphine, can now be done without the use of thebaine as starting material. The syntheses have fewer steps than previous methods, and also have high yields. In addition, very significant simplification of existing thebaine based processes for the manufacture of opiates can be expected.

 

Applications:

Potential new methodology for the synthesis of intermediates for drugs including naloxone, naltrexone, percodan and nalbuphine.

HHS Reference No. E-012-1986/1 --

• Australian Patent 642447 issued 15 Feb 1994
• Japanese Patent 2694156 issued 12 Sep 1997
• Canadian Patent 2067200 issued 30 Jun 1998
• European Patent 0496830 issued 31 Mar 1999 in Austria, Belguim, Switzerland, Germany, Denmark, Greece, Luxembourg, Spain, Belgium, Netherlands, Sweden, France, Italy and United Kingdom

 

HHS Reference No. E-012-1986/2 --

• United States Patent 5,668,285 issued 16 Sep 1997

 

Inventors:

Kenner C. Rice et al. (NIDDK)

 

 

Licensees sought.