Even though many of the syntheses have been known since the middle of the 20th century, researchers are still working today to further develop the synthesis of Dextromethorphan and, for example, to make it more environmentally friendly. This includes the synthesis by means of ionic liquids. Racemate separation
Since only one of the stereoisomers has the desired effect, the separation of a racemic mixture of hydroxy N- methyl morphinan using tartaric acid and subsequent methylation of the hydroxyl group is a suitable method. By using (D)-tartrate, the (+)-isomer remains as the product. This synthetic pathway was patented by Roche in 1950. Traditional synthesis
The traditional synthetic route uses Raney nickel and has been further improved over time, for example by the use of ibuprofen and AlCl3. Overall, it is a cost-effective method with moderate reaction conditions that is easy to handle and suitable for industrial production. Grewes cyclization
Grewes cyclization is easier to handle in terms of the chemicals used, produces higher yields and higher purity of the product. Improved Grewes cyclization
Formylation prior to cyclization avoids ether cleavage as a side reaction and yields higher than without N-substitution or N-methylation. In this example, the purification was done by formation of a brucine salt. This process has also been patented by Roche. History
The racemic parent compound racemorphan was first described in a Swiss and US patent application from Hoffmann-La Roche in 1946 and 1947, respectively; a patent was granted in 1950.
Individuals carrying this deficiency are relatively "normal", as in they do not possess any major birth defects or major medical illnesses. This microduplication is more common than the deletion; this might relate to the milder phenotype of the individuals. 22q13 deletion syndrome (Phelan–McDermid syndrome) is a condition caused by the deletion of the tip of the q arm on chromosome 22. Most individuals with this disorder experience cognitive delays, low muscle tone, and sleeping, eating, and behavioural issues. Chromosome ring 22 is a rare disorder caused by the break and rejoining of both ends of chromosome 22, forming a ring. The effects on the individual with this disorder are dependent on the amount of genetic information lost during the process. Major characteristics for this disorder are intellectual disability, muscle weakness, and lack of coordination. Cat eye syndrome (Schmid Fraccaro syndrome) is a condition caused by a partial trisomy or tetrasomy in chromosome 22. A small extra chromosome is found, made up of the top half of chromosome 22 and a portion of the q arm at the q11.2 break. This chromosome can be found three or four times. This syndrome is referred as "cat eye" due to the eye appearance of reported affected individuals who have coloboma of the iris, but this feature is only seen in about half of the cases. Mosaic trisomy 22 is a disorder in which an extra chromosome 22 is found only in some cells of the body.