Phenethylisoquinolines oxidation

An approach to the cephalotaxine skeleton, based upon the presumed biogenetic route, has been reported (164) and involves the oxidation of the 1-phenethylisoquinoline derivative (260) with VOF3 (Scheme 54). Alkaline cleavage of the dienone (261) gave 262 which, as the hydrochloride salt, was reduced 263. A-trifluoroacetylation followed by O-methylation yielded 264 which, after hydrogenolysis to 265, was oxidized with potassium ferricyanide to give the dienone (266). 

The oxidation of phenethylisoquinolines in biogenetically modelled syntheses has been studied. Orientaline, when oxidized with oxygen, copper(i) chloride, and pyridine, yields ( )-orientalinone, and the base (31) gives ( )-kreysiginone and its... 

Morphinandienones have also been synthesized by the oxidation of mono-phenolic benzylisoquinolines with vanadium oxyfluoride in trifluoroacetic acid, other products of the reaction being proaporphines, and similar oxidations have been accomplished with phenethylisoquinolines.183 The same reagent will oxidize the lactam (150) to the dienone (151), which is an analogue of dehydrometatheb-ainone, and the same cyclization may be effected by electrochemical oxidation.184... 

One-electron withdrawing inorganic reagents have been used to perform biomimetic syntheses of phenolic phenethylisoquinoline alkaloids. In order to obtain androcymbine compounds of type 85, the diphenolic isoquinoline 82a was subjected to phenol oxidation with manganese dioxide. The homoaporphine 83a coupled at the ortho-ortho position to the hydroxy group was the only product formed under these reaction... 

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. ... 

Androcymbine may be derived from phenethylisoquinoline 68 by phenol oxidation. The derivation of colchicine from phenethylisoquinoline precursors 67 and 68, which were formed from 65 and 66,... 

Oxidative coupling of phenethylisoquinolines. Treatment of ( )-N-trifluoro-acetylhomonorlaudanosine (1) with VOF3 and trifluoroacetic acid in CH2CI2... 

Autumnaline is a phenethylisoquinoline alkaloid, and possesses an additional Cj unit compared with the benzylisoquinoline alkaloids. Autumnaline, postulated to be the biosynthetic precursor of colchicine, was isolated from Colchicum cornigerutn (Colchicaceae) [4]. O-methylandrocymbine is formed through the intramolecular -oxidative phenolic coupling... 

The vanadium oxytrihalide oxidation of phenethylisoquinolines to neo-homoproaporphines and homoproaporphines is discussed in Sec. 29.2.2. 

Aqueous ferric chloride oxidation of the triphenolic phenethylisoquinoline 17a provided a 6% yield of the homoproaporphine... 

The crucial test for the hypothesis lay in the examination of compounds of type 6.171) and 6.173) as colchicine precursors. In the event [119-121], 0-methylandrocymbine 6.172) was a spectacularly good precursor for colchicine. The phenethylisoquinoline 6.171), called autumnaline, was also clearly implicated in biosynthesis only the (5)-isomer of autumnaline, with the same absolute configuration as colchicine is involved, and oxidative coupling of this base occurs in a para-para sense rather than the alternative, ortho-para. Results of other experiments, together with those discussed here, led to the pathway illustrated in Scheme 6.34. 

The manifold possibilities for the elaboration of structurally intriguing natural products via the aforementioned oxidative aryl-aryl coupling reactions emphasize the importance of phenolic coupling reactions in the biosynthesis of tyrosine-derived alkaloids. This important reaction not only plays a significant role in the biosynthesis of benzyltetrahydroisoquinoline alkaloids but also for the construction of phenethylisoquinoline alkaloids and Amaryllidaceae constituents, discussed in the following sections. 

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