Laudanosine Laudanosoline

Laudanosoline and Dehydrolaudanosaline. When laudanosine is de-methylated it yields laudanosoline, first prepared by Oberlin, ... 

Initially Robinson and Sugasawa (8) proposed that laudanosoline (5), prepared from laudanosine (4) by O-demethylation with aluminium chloride in refluxing xylene, could be oxidized to an aporphine or morphine prototype. To demonstrate that no rearrangement had occurred, 4 was regenerated from 5 by O-methylation. Oxidation of 5 was accomplished with chloranil in buffered alcohol solution, and 6 was isolated in 60% yield as the chloride (Scheme 1). Di-benzopyrrocoline 6 was also obtained in 30-50% yield when aqueous solutions... 

Attempts have been made to realize experimentally the conversion of laudanosine-type bases to bases of the aporphine and morphine series, so far without success. In an attempt to convert laudanosoline [xtx] to norglaucine [x ] it was discovered that the former is very readily oxidized to intractable materials, but that oxidation with chloranil [5-6] or tetrabromo-o-benzoquinone [7] affords, not the expected norglaucine, but 2 3 11 12-tetrahydro-8-methyldibenzotetrahydropyrrocolinium ohloride [xxi]. Protosinomenine [i] has been synthesized in two ways [3, 8], but the conditions required for the conversion of this base to sinomenine [iv] have not yet been realized and their discovery must be largely fortuitous [6],... 

In an eady attempt to understand the genesis of alkaloids from amino acids it was postulated (56) that intramolecular phenolic coupling should lead from benzylisoquinoline bases such as laudanosine (77, R = CH3), before it was completely methylated, to aporphine bases such as isothebaine (81). For example, between a benzylisoquinoline derived from laudanosoline (77, R = H), such as orientaline (82), and an aporphine alkaloid such as isothebaine (81), there should be a proaporphine alkaloid such as orientalinone (83) (56). The isolation of 83 lent credence to the hypothesis. Indeed, the fragile nature of 83 (it readily undeigoes the dienone—phenol rearrangement on acid treatment) required unusual skill in obtaining it from total plant extract. 

Demethylation of racemic laudanosine with 48 % hydrobromic acid (30) or anhydrous aluminum chloride (82) splits all four methoxyl groups and furnishes laudanosoline, but two or three methoxyl groups may be preserved if other reagents and milder conditions are chosen. When heated with 35 % hydrochloric acid at 100° for twenty minutes, all four possible monophenolic isomers are formed and may be isolated from the reaction mixture by fractional extraction and crystallization (83). They are lau-danine (LII) (m.p. 166-167°), pseudolaudanine (LIII) (m.p. 120-121°), DL-codamine (XXII) (oily), and pseudocodamine (LIV) (m.p. 129-130°). A discussion of their structure may be found on pages 57-63. 

As mentioned above, quaternary papaverinium salts were reduced to DL-laudanosine (XIII) under a variety of conditions (17, 28, 29, 30, 76). Alternatively, tetrahydropapaverine may be treated with methyl iodide to give DL-laudanosine hydriodide (85). The route from papaverine via protopapaverine and DL-laudanosoline 3, 4-dimethyl ether (LVII) has already been mentioned. Methylprotopapaverinium iodide can be reduced to DL-codamine (XXII), which can be methylated to DL-laudanosine. Not only DL-codamine but its three phenolic isomers (p. 53) can be converted to DL-laudanosine by the action of diazomethane (33, 83, 86). 

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