Pro-aporphines

Irradiation with sunlight of pakistanamine (63), which is the only known pro-aporphine-benzylisoquinoline alkaloid, yields lumipakistanine (64), together with a trace amount of neolumipakistanine (65),5 while it is known that the acid-catalysed rearrangement of (63) takes a different course and generates the dimer (66) (Scheme 4).45... 

Mecambroline was also obtained in 71 % yield by refluxing the pro-aporphine alkaloid mecambrine (VII) in dilute hydrochloric acid (6, ). 

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). 

D-( — )-Armepavine and l-( -t )-armepavine have been obtained by reductive cleavage with sodium-liquid ammonia of a number of bis-benzylisoquinoline alkaloids (11, 12). A similar treatment of the pro-aporphine alkaloid pronuciferine has produced d-( — )-armepavine, a method which permits the correlation of its configuration with the aporphine alkaloids (79). 

This is a 1,1-spirobenzyl intermediate to what is quite likely the entire family of the aporphines. The "pro" part of the name suggests that this is a biosynthetic precursor to these alkaloids. Very often there is a keto function at the 4-position of the benzyl group (equivalent to a hydroxyl group on the original benzyl), to facilitate the spiro loss of aromaticity needed to achieve this type of coupling. This is directly analogous to the (2,4a) attacks needed to get into the morphinans, where... 

Diphenylselenoxide has also been found to be a valuable oxidant for the synthesis of aporphines from non-basic diphenols and (134, R=H) is oxidised by this reagent in methanol at room temperature and after methylation of the crude product with diazomethane, y-trifluoroacetylnorthaliporphine is obtained in 80% yield. The process presumably proceeds through the orthoquinone and a non-basic nitrogen is essential if the pro-... 

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... 

---