Pethidine synthesis

Perylene-3,4,9,10-bis(dicarbonamide) electrical conductivity, 1, 358 Perylene hexafluoroarsenate conductors, 1, 355 Perylene vat dyes, 1, 336-337 Pestalotin synthesis, 3, 841 Pethidine... 

In an effort to more closely mimic the aromatic substitution pattern found in morphine (see A) the pethidine analog containing the m-hydroxy group was prepared as well. Thus, in a synthesis analogous to that used to prepare the parent compound, double alkylation of m-methoxyphenylacetonitrile with the chloroamine. 

Recently much interest has centred on a very specific toxin for DA neurons. This is 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). It was discovered when a student, who was addicted to pethidine, tried to manufacture l-methyl-4-phenyl-4-propionoxy-piperidine (MPPP) but took a short-cut in synthesis and produced MPTP. When he administered this to himself he developed Parkinsonism. MPTP destroys DA neurons. Again this process depends on the neuronal uptake mechanism, since MPTP itself is not the active material. It needs to be deaminated to MPP+ which is then taken up by DA nerve terminals. 

Pain research is a traditional and well established field within the pharmaceutical industry. Beginning with the isolation of morphine in a small pharmacy by Adam Serturner (1806), the next major breakthrough in pain treatment was achieved by the synthesis of acetylsalicylic acid by Felix Hoffmann in the Bayer Laboratories in Wuppertal (1897). Further outstanding contributions by the pharmaceutical industry were the first fully synthetic opioids pethidine (1939) and methadone (1946). Continued efforts up to now have resulted in many potent and clinically accepted analgesics with reasonable side effects and covering nearly all facets of pain treatment. However, pain treatment is far from being satisfactory in respect to more complex pain states, e.g. neuropathy, visceral pain or migraine. 

This means that it can be used to build up heavily branched esters and carboxylic acids—the sort that are hard to make by alkylation because of the problems of hindered enolates and unreactive secondary alkyl halides. Heavily substituted acids, where CO2H is attached to a tertiary carbon atom, would be hard to make by any other method. And the Favorskii rearrangement is a key step in this synthesis of the powerful painkiller Pethidine. 

A benzomorphan analog of pethidine, bearing a 6-ethoxycarbonyl group (155) was prepared by May et al.(95) by a modified 1-tetralone synthesis. It... 

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