Loading...
Please wait, while we are loading the content...
Similar Documents
Novel analgesics and molecular rearrangements in the morphine-thebaine group. 3. Alcohols of the 6,14-endo-ethenotetrahydrooripavine series and derived analogs of N-allylnormorphine and -norcodeine.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bentley, Kenneth W. Hardy, David G. |
| Copyright Year | 1967 |
| Abstract | Secondary and tertiary alcohols of general structures IV and V have been prepared by the demethyla-tion of the corresponding bases I and I1 described in part I1 of this series. The phenols so obtained are analgesics of extremely high potency, up to an unprecedented 12,000 times that of morphine. The bases of this and earlier series have been converted into analogs of N-allylnormorphine and N-allylnorcodeine of general structures XI and XI1 via the N-cyanonor compounds and via novel N,N'-methylenebis compounds XI11 resulting from the reaction of the bases I and I1 with methyl azodicarboxylate. Some bases of the series XI1 are morphine antagonists of unprecedented potency, up to 150 times that of N-allylnormorphine. n the preceeding paper the preparation of two series of I codeine derivatives of general structures I and I1 was reported, many of the members of which were considerably more active as analgesics than any base previously prepared in the morphine-thebaine group. Since the demethylation of codeine derivatives to the corresponding derivatives of morphine almost always results in an appreciable increase in analgesic activity, most of the alcohols of structures I and I1 were converted into the related phenols. The 0-demethylation cannot be accomplished without decomposition by acidic reagents owing to the extreme ease with which the alcohols undergo acid-catalyzed rearrangement,IC but was effected in most cases by heating the bases with potassium hydroxide in diethylene glycol at 200-220'. Demethylation of the methyl ethers to the phenols to a very small extent was occasionally observed during the Grignard reactions leading to the alcohols of structure I. The demethylating action of Grignard reagents is well known,2 but the method has little preparative value. The alkaline demethylations affected only the meth-oxy1 group attached to (2-3, that at C-6 remaining undisturbed. From the point of view of analgesic activity , however, the retention of the C-6 methoxyl group is advantageous, since methylation of the hy-droxyl group at this position in morphine and codeine enhances the activity. The demethylation of the C-3 methoxyl group in the codeine-thebaine group under alkaline conditions appears t o have been first observed during the Huang-Minlon reduction of thebenone. The 4,5-oxygen bridge in these bases, which is unaffected under the conditions of the demethylation, also represents the ether of a phenolic hydroxyl group, but fission of this bridge during simple demethylations in the morphine series has never been observed, though (1) (a) Part 11: K. |
| File Format | PDF HTM / HTML |
| DOI | 10.1021/ja00989a032 |
| PubMed reference number | 6042764 |
| Journal | Medline |
| Volume Number | 89 |
| Issue Number | 13 |
| Alternate Webpage(s) | http://index-of.co.uk/Tutorials-2/bentley-3.pdf |
| Alternate Webpage(s) | https://www.erowid.org/archive/rhodium/pdf/bentley-3.pdf |
| Alternate Webpage(s) | https://doi.org/10.1021/ja00989a032 |
| Journal | Journal of the American Chemical Society |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
