Synthetic routes from thebaine to l4β-acylaminodeoxydihydrocodeinones were explored. Each route was eventually frustrated by our inability to remove reductively either a 4-phenoxy or a 4-(1-phenyltetrazol- 5-yl)oxy group from a number of derivatives. Routes to the preparation of a thebaine derivative containing a piperidine nitrogen-carbon(14) bridge were investigated. In the N-northebaine series no bridged compounds were formed but in the thebaine series two quaternary ammonium chlorides with the desired bridge were prepared. Treatment of the cycloadduct 6β,14β-(N-chloroacetylepoxyimino)- 6,14-dihydro-N-t-butoxycarbonylnorthebaine with sodium ethoxide in ethanol afforded, unexpectedly, l4β-(2,2-diethoxyethanoylamino)-N-tbutoxycarbonylnorcodeinone. Similarly, the cycloadduct 6β,14β- (N-phenylacetylepoxyimino)-6,14-dihydrothebaine was found to react with high stereoselectivity with methoxide to give l4β-[(S)-2-methoxy-2- phenylethanoylamino]codeinone. Treatment of the hydroxamic acid l4β-(N-2-phenylethanoylhydroxyamino)codeinone with toluene-p-sulphonyl chloride in pyridine followed by methoxide gave a yellow product which had incorporated one molecule of pyridine. All the foregoing reactions are believed to proceed via aziridinone (α-lactam) intermediates. Further studies on model compounds supported the proposed mechanisms. An alternative, high yielding synthesis of the known a-lactam, l-t-butyl- 3-phenylaziridin-2-one, has been achieved by treating the appropriate hydroxamic acid with trifluoromethanesulphonic anhydride and triethylamine at 700 C. The reaction of the hydroxamic acid l4β-(N-chloroacetylhydroxyamino)- N-t-butoxycarbonylnorcodeinone ethylene acetal with ethoxide gave the l4β-aminonorcodeinone derivative. A similar treatment of the corresponding hydroxamic acid derived from thebaine and also of model compounds yielded ester products. These reactions are rationalised in terms of oxazetidinone intermediates.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:238358 |
| Date | January 1982 |
| Creators | Bladon, Christine Mary |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/5534/ |
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