Aporphines absolute configuration

Oxidative coupling of (5)-(-)-laudanosoline (5) with horseradish peroxidase in the presence of hydrogen peroxide, studied by Brossi et al. (27), afforded dibenzopyrrocoline (—)-6 in 81% yield, and conversion to (5)-(—)-0-meth-ylcryptaustoline (14) by methylation provided additional proof for the absolute configuration of this and related alkaloids. Enzyme specificity in the C— coupling reaction was demonstrated with similar oxidation of (/ )-(—)-laudanosoline methiodide, which afforded an aporphine converted by O-meth-ylation to (R)-(-)-glaucine. 

The second dimeric base, (—)-pennsylpavoline (179), was shown to correspond to C-l-demethylpennsylpavine. Specifically, its NMR spectrum was devoid of the 8 3.71 singlet which represents the C-1 methoxyl absorption in (—)-pennsylpavine (178). Evaluation of CD spectra of these novel dimers and comparison with those of the aporphine (+)-A -methyllaurotetanine and the pavine (—)-platycerine led to the assignment of the absolute configurations as depicted in expressions 178 and 179. These dimers are probably derived biosynthetically from the aporphine-benzylisoquinoline dimers, (-)-pennsylvanine and (-)-pennsylvanamine, which were found in the same plant (7,173). 

Since previous work on the aporphine alkaloids had shown that the absolute configuration may be determined from the sign of their high-amplitude Cotton effect centered at 235-245 nm and that the positive Cotton effect corresponds to (S) configuration of a twisted diphenyl system, the coincidence of the CD curves of (— )-anhydrolycorine methiodide and (+ )-anhydrolycorine methiodide at 240 nm with those... 

The circular dichroism curves of nineteen aporphines have been examined. A generalization worth bearing in mind is that the terminal absorption near 216 nm is positive in the case of the R configuration, and negative for the S.53 A study of natural (—)-crebanine confirmed the R absolute configuration, instead of the S configuration which is usual for aporphines that are disubstituted in ring d. 

The aporphine alkaloids contain a twisted biphenyl system, and can exist either in the absolute configuration (LXXIX S series) or its mirror image (LXXX R series) (61). 

II) t3q>es. The absolute configuration of (-f )-norlaudanosine was elucidated by adopting a degradative method (isolation of i T-a-carb-oxyethyl-L-aspartic acid) 115), which in turn permitted the establishment of the absolute configuration of the proaporphine, aporphine, pro-morphinane, morphinane, and tetrahydroprotoberberine alkaloids (Scheme 20). The optical rotatory data 63), the ORD-curves 2, 41,120, 122), and the CD-curves 73) have led to an accumulation of sufficient information for the determination of the absolute configuration even of... 

The reduction with borohydride and the acid-catalyzed dienone-phenol/dienol-benzene rearrangements leave the center of chirality at C-6a intact. Consequently, the absolute configuration of this center can be intercorrelated with that of the benzylisoquinoline, proaporphine, and aporphine alkaloids (Schemes 1, 2, and 20). 

The proaporphine, promorphinane, and cularine alkaloids can be reconverted into the benzyltetrahydroisoquinoline bases with sodium in liquid ammonia, a process which permits correlation of the absolute configurations of the benzyltetrahydroisoquinoline, proaporphine, aporphine, promorphinane, and cularine alkaloids (375). 

More recently, the preparative value of VOCl3 and VOF3-TFA in chemical oxidation has been demonstrated (see Section III, on the pro-aporphine and promorphinane alkaloids) (415,462). Some other authors used the purified enzyme horseradish peroxidase (463). By this method the aporphine base (besides the quaternary dibenzopyrrocoline) is readily obtained from (S)-( + )-laudanosoline hydrobromide or from (/ )-(—)-laudanosoline methiodide with retention of the absolute configuration. The synthesis of 6a,7-dehydroaporphine bases was also carried out by making use of the benzyne reaction (439). Reduction of these substances affords the corresponding aporphine bases (439). The synthesis of isoquinoline alkaloids by lead tetraacetate oxidation was reviewed by Umezawa and Hoshino (343). 

Alkaloids with one chiral carbon are shown as racemic mixtures, but their enantiomeric characterization is given in the text with the prefix (-) or (-I-). In the formulas of alkaloids with more than one chiral center the relative and absolute configurations are omitted. However, these structural details can be found in the literature [Refs. 3-8, 16, and previous volumes of this treatise Simple Isoquinolines, Vol. 21 (1983), p. 255 Aporphines, Vol. 24 (1985), p. 153 Phthalideisoquinolines, Vol. 24 (1985), p. 253 Benzophenanthridines, Vol. 26 (1985), p. 185]. 

Of particular interest is calycinine, which possesses a meta substitution pattern in ring D, and fuseine, which is the first simple lactam known in the aporphine series. A complete X-ray analysis was carried out on the 7V,0-diacetyl derivative of 4-hydroxynornantenine to confirm its stereochemistry and absolute configuration. " The stereochemical assignments for all 4-hydroxylated apor-phines are, therefore, predicated upon this X-ray study. 

Substituents are related to absolute configuration by the following simple rule Aporphines substituted at both C-10 and C-11, or at both C-9 and C-10, are usually dextrorotatory and belong to the L(5)-series. Aporphines unsubstituted or monosubstituted in ring D can belong either to the L(5)- or the i)(R)-series. 

The CD curves of several aporphines have been measured, and these have been correlated with the absolute configurations. ... 

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