Laudanosine oxide

Laudanosine contains four methoxyl groups. By exhaustive methyla-tion it yields trimethylamine and laudanosene (tetramethoxy-o-vinyl-stilbene), CH2=CH—C6H2(OCH3)2—CH=CH—C6H3(OCH3),. On oxidation with manganese dioxide and sulphuric acid it furnishes, in addition to the interesting by-product 2 3 6 7-tetramethoxy-9 10-dihydroanthracene, veratraldehyde and 4 5-dimethoxy-2 )3-methyl-... 

A complete synthesis of laudanosine was effected by Pictet and Finkelstein by the condensation of omoveratrylamine (I) with homo-veratroyl chloride (II), giving omoveratroyl omoveratrylamine, which with phosphoric oxide undergoes cyclisation to 3 4-dihydropapaverine (III), which was converted into the methochloride and reduced to laudanosine (IV). 

The first postulate may be illustrated by the still unrealised conversion of laudanosine into glaucine by oxidation, resulting in the loss of one atom of hydrogen from each aromatic nucleus and union of these as shown by the dotted line. 

These substrates possess several oxidiz-able sites. Racemic laudanosine (71), for example, could be oxidized at nitrogen or in one or both of the electron-rich aromatic rings. In fact, it displays ve volta-metric peak potentials at 0.63, 0.81, 1.13, 1.30,andl.47 V(vsAg/AgN03). Yet,using potential control, it proved a simple matter to oxidize a dimethoxyaryl unit in the presence of the Ai-methylamine subunit. 

Oxidative caibon-carbon bond formation from laudanosine derivatives generally favours a 6-membered ring. Severe steric constraints result in exceptions to this rule. Oxidation of the bridged ether derivative 34 results in carbon-carbon bond formation to form a 5-membered ring product and this process has been used for one stage in the synthesis of erythrina alkaloids [138]. Some of the morphinadie-none system is also formed, in spite of the steric constraint imposed by the ether-bridge. 

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... 

Following the structure proof of the alkaloids by degradation, Hughes et al. (.18) synthesized (—)-0-methylcryptaustoline iodide (14) by methods elaborated by Schopf and Robinson. ( )-Laudanosine was resolved by quinic acid (79), and (S)-(-)-laudanosine was 0-demethylated by Schopf s procedure, oxidized by chloranil, and remethylated to afford chiral 14 as the iodide in 40% yield. Their product had the same specific rotation and melting point as O-methylcryp-taustoline iodide obtained from the natural alkaloid 1. Methine derivatives obtained from synthetic and natural compounds had identical optical properties. 

The synthetic utility of anodic reactions that couple aromatic rings activated by alkoxy groups has been explored for the formation of natural products. Thus laudanosine (78 R1 = R2 = R3 = R4 = CH3) has been oxidized... 

The benzylisoquinoline alkaloids are widely distributed in nature and are intermediates in the biosynthesis of alkaloids of this family (2, 3). It is not surprising therefore that several groups (6, 7, 15, 23) have examined their spectra. Among the alkaloids that have been studied are reticuline (26) (7), norlaudanosine (27) (7), laudanosine (28) (6, 15), and the cis- and trans-N-oxides of laudanosine, 29 and 30, respectively (7). The chemical shifts of laudanosine are recorded in Table IV and the structures of the alkaloids may be found in Fig. 4. 

Morphine alkaloids are a subgroup of isoquinoline alkaloids and are derived biogenetically from laudanosine bases by oxidative phenolic coupling/6,7 Alkaloids of the opposite enantiomorphic group occur in several Japanese Sinomenium and Stephania species, the most important compounds being sinomenine, hasubanonine, metaphenin, and protometaphenine. 

The alkaloid was found to contain two methylimino groups, seven methoxyl groups, and one diphenyl ether linkage. Oxidation of fetidine with permanganate gave l-oxo-2-methyl-6,7-dimethoxy-l,2,3,4-tetra-hydroisoquinoline. Reduction with sodium in liquid ammonia furnished (+ )-laudanosine (XLI) and (-I- )-laudanidine (XXXII). Thus it was concluded that the alkaloid is represented by formula LII, or a variation of this formula having the ether linkage attached to C-10 or C-14. 

Another interesting finding is that electrolytic oxidation of laudanosine (15b) in TFA affords a 17% yield of glaucine (20) the presumed intermediate again being a morphinandienone. ... 

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],... 

Both cis and trans laudanosine 4 -oxides (39) have been prepared. On pyrolysis the trans oxide gives only the product of Cope degradation (40), whereas the cis oxide gives in addition the rearranged bases (41), (42) and (43). (J.B. Bremner and... 

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