Brucine, transformation

Other investigations of interest are the studies of the isomeric dihydroderivatives of brucine and strychnine and their reactions, carried out by Leuchs and his collaborators, investigation of the red o-quinone (isolated as the perchlorate, CjiHjoO Ng. HCIO4) formed in the well-known test for brucine with nitric acid, and the examination of the transformation products of oximinobrucine by Wieland et al. ... 

In the optical resolution of cyanohydrins, it was first found that brucine (4) is a suitable host for the cyanohydrins which substituted with one aromatic group and one bulky alkyl group. In this case, not only a simple enantiomer separation of rac-cyanohydrin but also its transformation to one enantiomer occurred and one pure enantiomer was obtained in a yield of more than 100%. For example, when a solution of rac-l-cyano-2,2-dimethyl-l-phenylpropanol (61a) (1.0 g, 5.3 mmol) and 4 (2.1 g, 5.3 mmol) in MeOH (2 ml) was kept in a capped flask for 12 h, a 1 1 brucine complex of (+)-61a (2.08 g, 134%, mp 112-114 °C) separated out as colorless prisms. Decomposition of the complex with dil HC1 gave (+)-61a of 97% ee (0.67 g, 134%). From the filtrate, rac-61a (0.33 g, 33%) was obtained.273 The... 

Crystallization-induced asymmetric transformation has already been described by Leuchs in 1913 during the resolution of 2-(2-carboxybenzyl)-l-indanone with brucine.34 In this case spontaneous racemization occurred. More recently researchers at Sanofi observed spontaneous racemization during the resolution of 3-cyano-3-(3,4-dichlorophenyl)propionic acid (7), most likely as a result of the basic resolving agent [>-(-)-N-1 n etli y I g I near nine [d-(-)-MGA] (8) (Scheme 7.6).35 The enantiopure cyano acid, obtained in 91% overall yield, is subsequently reduced to (+)-4-amino-3-(3,4-dichlorophenyl)-l-butanol (9), a key intermediate in the phase 2 synthesis of tachykinin antagonists. 

Chart VI Strychnine and Brucine and Their Products of Transformation and Degradation. 419... 

The relationship of the more important products of transformation and degradation of strychnine and brucine are graphically illustrated in Chart VI. 

The dimethoxybenzene nucleus of brucine (159), its methosulfate (82), dihydrobrucine (159), the brucinesulfonic acids (60, 93), pseudobrucine and its dihydro derivative (162, 165), iV-methyl-sec-pseudobrucine (168) as well as that of a number of transformation products of brucine (brucinonic acid (126), brucinolic acid (126), dihydrobrucinonic acid (126), bromo-dihydrodesoxybrucine (32), and dihydrodesoxybrucine (32)) is attacked by nitric acid (chromic acid in a few instances) at 0-5° with the formation of the respective o-quinones, which in turn may be reduced (SO2) to the respective colorless hydroquinones (or isomerized by HCl to colored isomers). More vigorous conditions (temperature and concentration of the oxidant) effect a simultaneous nitration of the quinone nucleus and a hydrolysis of the lactam grouping. 

Brucine is oxidized by 5 V nitric acid (or chromic acid (159)) at 0-5° to a rose-colored solution from which a red bruciquinone (bis-desmethylbrucine, (C21H20O4N2), XCIII) can be isolated as its perchlorate. It is a typical quinone because it is reduced by sulfurous acid to a hydroquinone, bis-apomethylbrucine (diacetate formation brucine yields two moles of methyl chloride when heated with hydrochloric acid but bis-apomethylbrucine could not be isolated from the reaction mixture (191) ). No other alterations occur in the brucine molecule during these transformations since methylation (dimethyl sulfate) converts bis-apomethylbrucine to the quaternary salt of brucine. The hydroquinone has been oxidized, with... 

Thusy Mills and Elliott (105) found that on crystallizing the brucine salt of JV-benzenesulfonyl-8-nitro-l-naphthylglycine (VIII) from two different solvents, acetone and methyl alcohol, an asymmetric transformation can be effected at will in two opposite senses. In effect, a novel type of resolution is achieved in this special case ... 

As early as 1904, Marckwald et al. [4] reported the thermal decarboxylation of ethyl(methyl)malonic acid 1 at 170°C in the presence of brucine affording (S)-2-methylbutyric acid 2 in 10% ee (Scheme 3.2). While this report might probably be considered as the first asymmetric transformation, this result could not be successfully reproduced several decades later [6]. In 1975, Verbit et al. [7] reported the decarboxylation of ethylphenylmalonic acid 3 in cholesteryl benzoate at 160°C giving rise to (/ )-phenylbutanoic acid 4 in 18% ee (Scheme 3.2). However, Kagan et al. [8] failed to obtain any enantioenriched phenylbutanoic acid 4 under the same reaction conditions. 

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