Desoxycodeine synthesis

A novel approach towards the construction of the morphine skeleton is demonstrated by the total synthesis of ( )-desoxycodeine-D. One of the key steps for this synthesis is the palladium-catalyzed intramolecular Heck reaction. Therefore, this synthetic strategy for the construction of the polycyclic ring systems has provided an efficient access to the complete pentacyclic skeleton of morphine <00TL915>. 

A new approach to the morphine skeleton was demonstrated by the total synthesis of (+)-desoxycodeine-D by C.-Y. Cheng and co-workers." " The key step was the formation of the B ring by the Stevens rearrangement of a tetrahydroisoquinoline-derived quaternary ammonium salt upon treatment with phenyllithium. 

Final proof of the Gulland and Robinson formulae for the morphine alkaloids has been obtained by the synthesis of racemic tetrahydro-desoxycodeine [lxiv] by Grewe, Mondon, and Nolte [94] and of dl-dihydrodesoxycodeine-B methyl ether [lxv] by Gates and Tschudi [95], The former, whilst fixing the point of attachment of the nitrogen end of the side-chain, did not eliminate the possibility of a spirane structure such as [Lxm], but the latter definitely established the location of the carbon end of the side-chain at C-13. (See Chap. XXVIII.)... 

Bromination of the aromatic nucleus occurs when desoxycodeine-A is treated with bromine, and the hydrogen bromide thus formed adds (1 4 ) to the diene system, giving dibromodihydrodesoxycodeine, also obtained by addition of hydrogen bromide to desoxycodeine-A followed by bromination. Acetolysisofthe dibromide yields l-bromo-3-methoxy-4-acetoxyphenanthrene (structure proved by conversion to the 3 4-dimethoxycompound and synthesis of the latter), also prepared by the degradation of 1-bromocodeine [5]. 

Liou J-P, Cheng C-Y. Total synthesis of ( )-desoxycodeine a novel route to the morphine skeleton. Tetrahedron Lett. 2000 41(6) 915-918. 

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