Phenethylisoquinoline

These alkaloids have a phenyl or phenylpropyl nucleus. The group includes simple phenyl amine (tyramine, hordenine), catecholamine (dopamine, noradrenaline, adrenaline), simple tetrahydroisoquinoline (mescaline, anhalamine, anhalonine, anhalonidine), benzylisoquinoline (e.g., papaverine), phthalideiso-quinoline (e.g., noscapine), phenethylisoquinoline (autumnaline, floramultine and kreysigine), tetrahydroisoquinoline (emehne and cephaeline) and terpenoid tetrahydroisoquinoline (secologanin and ipecoside) alkaloids. 

The first homopavine, ( )-homoargemonine (174), was synthesized in 1973 in an attempt to construct pavine analogs with improved analgesic activity (Scheme 38) (777). The corresponding 1-phenethylisoquinoline 173 was obtained by a Bischler-Napieralski condensation of 2-(3,4-dimethoxyphenyl)-ethylamine (170) and 3-(3,4-dimethoxyphenyl)propionic acid (171) via the hy-droxyamide intermediate 172. Compound 173 was then successively quater-nized, reduced by lithium aluminum hydride, and treated with acid to afford the tetracyclic compound ( )-174. 

Magnolio- phyta (Ang.)> 250,000/50 Goom. 1992 Land ALKAL. benzyl phenylethyl, benzyltetraisoquinoline, indolizinoquinoline, phenethylamine, phenethylisoquinoline, terpenoid (secoloeanin). ISOPR. Monotem. iridoids Tritem. oleane hi high... 

J. Other isoquinoline alkaloids phenethylisoquinolines, emetine, pavines, tetra-... 

Lilaceae also contain 1-phenethylisoquinoline alkaloids, it was suggested [82) that the homoerythrina derivatives are biosynthesized along a pathway analogous to that followed by the Erythrina alkaloids themselves (Scheme 35). Some preliminary results from feeding experiments (121) support this view ( )-[2-14C]tyrosine causes specific labeling of C-8 in 77a. 

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). 

Cephalotaxus Alkaloids.—Preliminary results indicate that the homo-Erythrina alkaloid schelhammeridine (52) derives from phenylalanine and tyrosine by way of a phenethylisoquinoline precursor [as (53)].52 Previous evidence for the biosynthesis of the related alkaloid cephalotaxine (54), obtained with tyrosine labelled in the side-chain, has indicated a different pathway which involves two molecules of this amino-acid.53 Recently, however, tyrosine labelled in the aromatic ring was examined as a cephalotaxine precursor and was found54 to label ring A of (54) almost exclusively, i.e. only one unit of tyrosine is used for biosynthesis. This is obviously inconsistent with the previous evidence and the early incorporations are... 

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... 

The isoquinoline alkaloids are the second largest group of alkaloids, numbering about 6000, and can be viewed as five subgroups—the simple tetrahydroisoquinolines, the benzylisoquinolines, the phenethylisoquinolines, the Amaryllidaceae alkaloids, and the monoterpene isoquinolines. In addition, there are a number of simple phenethylamine derivatives, including ephedrine (originally from Ephedra species, but now synthesized) and pseudoephedrine, used for asthma and nasal... 

Nasreen, A. Gundlach, H. Zenk, M.H. Incorporation of phenethylisoquinolines into colchicine in isolated seeds of Colchicum autumnale. Phytochemistry 1997, 46, 107-115. 

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