Isothebaine

During the period of growth of the oriental poppy, Papaver orientale, the plant contains appreciable amounts of thebaine, but during late fall, after ripening and dying of the aerial plant, little, if any, of this alkaloid is to be found, but at this time an optically active base, isomeric with thebaine, may be isolated from the root of the poppy. This base, called isothebaine, was first isolated by Gadamer [1-2] as an unidentified phenolic alkaloid and subsequently examined by Klee [3]. It has also been shown to be present in Papaver bracteatum [4], 

Klee [3] recorded the following colour tests for the alkaloid  

The trimethoxyphenanthrene obtained by the degradation of isothebaine methyl ether is oxidized by nitric acid to benzene-1 2 3 4-tetracarboxylic acid [5]. (Compare the production of the same acid as final product of oxidation of 3 4 6-trimethoxyphenanthrene [9-10].) 

Hofmann degradation of isothebaine methiodide gives a resinous methine base degradation of which involves loss of trimethylamine and production tars [6], The oxidation of isothebaine and its methyl ether with iodine gives only green, amorphous substances [3]. 

The ultra-violet absorption spectrum of isothebaine has been studied by Girardet [11]. It is shown with that of morphothebaine in Fig. 17. 

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Among other formulae which must be mentioned are those of Vis, which represents morphine as a benzyh soquinoline, Vongerichten, Bucherer, Gadamer and Klee, devised to account for the possible natural formation in P. orientate of isothebaine from thebaine, and the vinyl formula of Wieland and Kappelmeier. ... 

On oxidation, Isothebaine (145) forms 6a,7-Didehydroisothebaine (146) as well as PO-3 129, which can be protonated to give a red substance. Both alkaloid gives Isothebain on reduction (69MI2) (Scheme 52). 

Stephanine (Figure 6.60) from Stephania species (Menispermaceae) is analogous to isothebaine and shares a similar pathway, though from... 

Isothebaine (2,11-dimethoxy-l-hydroxyaporphine) was isolated for the first time by Gadamer and Klee (394) from P. orientale L. In isolated normal intestine of rabbits and rats and in that tonicized by enterotonine smaller doses of isothebaine brought about a rise of the muscle tonus whereas higher doses produced relaxation (395, 396). Experiments carried out on the rat uterus in situ showed that isothebaine amplified the tonus and contractions but it did not affect the action of oxytocin. It slowed down significantly the frequency of respiration and the pulse rate. In mice it decreased the motor activity... 

Isothebaine (= 1-Hydroxy-2,1 1-dimethoxyaporphine) (aporphine isoquinoline) Laudanosine (= Laudanine methyl ether) (benzylisoquinoline)... 

The dienol-benzene rearrangement has been used to advantage to explain the structures of several abnormal aporphine alkaloids (49) from a biogenetic point of view, and has also allowed the first s3uithesis of the aporphine alkaloid isothebaine (L) (50). (+ )-Orientaline (XLVII) was oxidized by alkaline ferricyanide to give a mixture of two dienones (XLVIII) in 4% yield. One of the dienones was reduced with sodium borohydride to a mixture of two dienols XLIX which, without... 

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