Sinomenine 1-bromo

The nature of this substance was first elucidated by Schopf and Pfeiffer [54], who, following the conversion of dihydrothebainone [xi/vm], through 1 5-dibromodihydrothebainone [xlix] to 1-bromodihydroco-deinone [l] by bromination and treatment with alkali, and the similar conversion of 14-hydroxydihydrothebainone [li] to 1-bromo-l 4-hydroxy -dihydrocodeinone [lit], showed that 1-bromosinomeneine results in 80 per cent, yield from treating sinomenine with bromine and then with alkali [54], The intermediate 1 5-dibromosinomenine [un] has boon isolated and converted to 1-bromosinomeneine by warming... 

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). 

Methoxy-4 6-diacetoxyphenanthrene [nr] is formed when codeinone [lii] [68] and sinomenine hydrate [un] [69] axe heated with acetic anhydride and sodium acetate a second product in the degradation of [lih] is triacetyh sothebenine [liv ]. The 1-bromo-derivative can be obtained in like manner from the antipodes of 1-bromosino-meninone [69-70] and reduced catalytically to [li]. Hydrolysis of [li] affords the corresponding 4 6-dihydroxy-compound, which results from heating codeinone methiodide with ethanol at 160° C. [71] both compounds have been identified by conversion to 3 4 6-trimethoxy-phenanthrene [68],... 

The positions of the oxygen substituents in sinomenine was demonstrated by the identity of dimethylsinomenol [xcvil] with 3 4 6 7-tetramethoxyphenanthrene. This was synthesized by Pschorr s method from 2-nitroveratric aldehyde and 3 4-dimethoxyphenylacetic acid, a synthesis that afforded two tetramethoxyphenanthrene-9-carboxyhc acids, [xcvm] and [xoix], one of which, [xcvm], being also accessible from the bromo-acid [c] must be the 3 4 5 6-isomer the other [xcix], which must therefor be the 3 4 6 7-isomer, gave dimethylsinomenol on decarboxylation [103, 105-6],... 

In marked contrast to codeinone [lii], of which it is a derivative, 1-bromosinomeneine [cm] can be degraded to methine bases, of which two are known, viz. 1-bromosinomeneine methine [crv] [107] and 1-bromodehydrometasinomenine methine [cv] [111]. The acetolysis of 1-bromosinomeneine [cm] affords 1-bromodiacetylsinomeneine [ovi] together with a small quantity of 1-bromodiacetylsinomenol [cvn], which is also obtained by the acetolysis of 1-bromosinomenine, 1-bromo-sinomenine methine, 1-bromosinomenein methine [civ] [112], and 1-bromodehydrometasinomenine methine [cv] [111]. Catalytic reduction of [evil] yields diacetylsinomenol [112]. 

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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