Sinomeninone 1-bromo

Methoxycodeine (139) has been prepared 222 from (-)-l-bromo-sinomeninone (138) in three stages (Scheme 2.18), and found to be about 5 codeine (MHP, sc). In view of the acid instability of 7-methoxycodeine it was surprising to find that it was an equivalent analgesic to codeine when administered po. Perhaps the standard error limits of the biological test were wide enough to suggest that the compounds were equipotent. 

The bromination of sinomenine hydrate with three equivalents of bromine and of 1-bromosinomeninone with two equivalents of bromine yields 1 5 8-tribromosinomeninone, which is converted into 1-bromo-sinomeninone by catalytic reduction, and to 1-bromodesmethoxydesoxy-dihydrosinomenine on reduction by Clemmensen s method [69]. 

Diacetoxy-3-methoxyphenanthrene and triacetylisothebenine are obtained by the acetolysis of sinomenine hydrate and the 1-bromo-derivatives of these can be prepared in the same way from 1-bromosinomeninone. Catalytic reduction of both triacetylisothebenine and its 1-bromo-derivative affords triacetyl-9 10-dihydroisothebenine [55], believed by Schopf, Pfeiffer, and Hirsch [64] to be triacetylisothebenine when the same sequence of reactions was carried out on (—)-l-bromo-sinomeninone. /sothebenine is probably 4 6-dihydroxy-3-methoxy-5-(/3-methylaminoethyl)-phenanthrene [lxxxh], or the 4 7-dihydroxy-isomer [64], On heating with sodium hydroxide and methyl alcohol at 80° C., 1-bromotriacetyKsothebenine yields a compound C2oH2004NBr in 7 per cent, yield this is probably 1 -bromo-N-acetylisothebenine [55] (see also Chap. XXV). 

Further degradation of 1-bromosinomeninone furazan methine yields l-bromo-9 10-dehydro-(—)-thebenone ketone furazan, which cannot be prepared by the bromination of [Lxxxvm] as this reaction gives the isomeric 9 -bromo-derivative. The Hofmann degradation of 1 9 -dibromosinomeninone furazan methine and the bromination of [Lxxxvm] and its 1- and 9 -bromo-derivatives all yield, finally, 1 9 -dibromo-9 10-dehydro-(—)-thebenone ketone furazan. l-Bromo-(—)-thebenone ketone furazan may be prepared either by the bromination of [lxxxix] or by the bromination of sinomeninone furazan dihydro-methine, followed by the degradation of the resulting 1-bromo-deriva-tive [51-52]. 

Methoxycodeine (154) has been prepared from l-bromo-(—)-sinomeninone (151 R = Br) via l-bromo-(+)-sinomenine (152), which on bromination and cyclization with alkali yields l-bromo-7-methoxycodeinone (153) this, on reduction with lithium aluminium hydride, yields (154). This derivative of codeine is an orally active analgesic, in spite of the fact that it is unstable to acids, which convert it into the inactive (-)-sinomeninone (151 R = H). ... 

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See also in sourсe #XX -- [ , , , , , , ]

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