The Homoaporphines and Homoproaporphines

Several homoaporphines and reduced homoproaporphines have recently been isolated from members of the Liliaceae, mostly by the Russian school. The assigned structures are reproduced below. However, in the case of the reduced proaporphines, the data available are fragmentary, and some of the stereochemical assignments still remain to be made or to be confirmed. 

Bechuanine and merenderine are identical in all respects, and correspond to the S -( + )-enantiomer of the known homoaporphine (—)-floramultine. The reduced homoproaporphine ( + )-yolantamine (jolantamine, jolanthamine) is diastereomeric with (-h)-bulbocodine. ( + )-Kesselringine and (-h)-luteine are diastereomers possessing identical stereochemistry at C-6a. 

Comparative mass spectral studies of yolantamine, bulbocodine, kessel-ringine, and regelamine have been carried out.  

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Cyclization of (147 R = CH2Ph) by the action of trifluoroacetic acid yields androcymbine benzyl ether (148 R = CH2Ph), which has been converted into androcymbine (148 R = H) androcymbine methyl ether (148 R = Me) has been prepared from (147 R = Me) in a similar manner. Homoaporphines and homoproaporphines are produced, as well as homomorphinandienones, during this cyclization.378... 

Homoaporphines and Homoproaporphines.—A new homoaporphine from C. cornigerum is CC-24 (219). Photolysis of the appropriate bromotetrahydro-phenethylisoquinolines can lead to racemic multifloramine (218), kreysigine (220), or 0-methylkreysiginone (221). In each of these syntheses the bromine is situated either at C-8 or at C-2 of the tetrahydrophenethylisoquinoline precursor. ... 

The oxidation of phenolic phenethylisoquinolines has been studied in some detail. With iron(iii) chloride the bases (68 R = H and R = OMe) have been oxidised to the homoproaporphine bases (69 R = H and OMe), and the base (70) has been oxidised to the homoproaporphine (71), which yielded the homoaporphine alkaloid multifloramine when subjected to dienone-phenol rearrangement. In this last process, when the dienone (71) was treated with concentrated hydrochloric acid in glacial acetic acid, the mixed acetal (72 R = Me), convertible into the hemiacetal (72 R = H), was isolated. ... 

By analogy with the biosynthesis of several aporphine alkaloids (33-35) the homoaporphines could arise naturally by way of homoproaporphines 78a and 78b or by direct coupling of the diphenolic isoquinoline 77a. 

The homoaporphines, e.g., floramultine, multiflora-mine, and kreysigine as well as the homoproaporphines are formed, similar to the bis-phenethylisoquinolines. 

A modification of the above procedure gave three types of products, C-homoaporphines 129-131, homoproaporphines 132 and 133 (see Section IV), and homomorphinandienones 134 and 135 (except for 118 see Section V) (57). LTA oxidation in AcOH of ( )-l-phenethyltetrahydro-isoquinolin-7-ol 117 gave a p-quinol acetate l20, TFA treatment of which in CH2CI2 produced the ( )-C-homoaporphine 129 in 44.2% yield. Similarly, the ( )-C-homoaporphines 130 and 131 were prepared in 55 and 35.2% yield, respectively, from the ( )-l-phenethyltetrahydro-isoquinolin-7-ols 118 and 119 (Scheme 15). 

As mentioned in Section III, we found that LTA oxidation in AcOH and subsequent TFA treatment of the ( )-l-phenethyltetrahydro-isoquinolin-7-ols 117 and 136 afforded ( )-l-hydroxy-2,10-dimethoxy-homoproaporphine (132) in 6.9 and 15.5% yield, respectively, which corresponded to dienone II 60, as well as ( )-C-homoaporphines 129 and 139 and ( )-homomorphinandienones 134 and 143 (see Section V) (57) (Scheme 15). The stereostructure of dienone II was determined as 197 by an X-ray crystallographic analysis of its derivative (,57,61,62). For another spiroisomer named dienone I, the naturally occurring ( )-kreysi-ginone (63), the above experiment in turn established the correct stereostructure as 198. In an analogous manner, the ( )-l-phenethyltetrahydro-isoquinolin-7-ols 137 and 138 afforded ( )-10-benzyloxy-l-hydroxy-2-methoxyhomoproaporphine (142) and ( )-12-methoxykreysiginone (133) in 11.4 and 15.9% yield, respectively, together with ( )-C-homo-aporphines 140 and 141 and ( )-homomorphinandienones 144 and 145 (see Sections III and V) (Scheme 15). 

Phenethylisoquinoline alkaloids are classified into seven major alkaloid groups based on structural differences simple 1-phenethylisoquinolines (1), homomorphinanedienones (2), bisphenethylisoquinolines (3), homoproaporphines (4), homoaporphines (5), homoerythrines (6), and dibenz[benzylisoquinoline alkaloids. Although tropolone and Cephalotaxus alkaloids also belong to the... 

Phenethylisoquinoline alkaloids are classified into six major alkaloid groups based on structural differences, namely, simple 1-phenethyliso-quinoline (1), homomorphinandienone (2), bisphenethylisoquinoline (3), homoproaporphine (4), homoaporphine (5), and homoerythrina alkaloids (6). These alkaloids are related to the benzylisoquinoline alkaloids such as morphinandienone, bisbenzylisoquinoline, proaporphine, apor-phine, and erythrina alkaloids. Although colchicine and its derivatives also belong to the phenethylisoquinoline alkaloids group, these alkaloids are not included in this review as they have been reviewed earlier 1). 

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