Isoquinolines => phenethylamines

BISCHLER NAPIERALSKI Isoquinoline synthesis Isoqutnoline synthesis Irom amides of phenethylamines... 

The thermal condensetion of p-benzyloxyphenylacetic acid and of 3-methoxy-4-hydroxy-phenethylamine occurs and gives, with a yield of 86% to 92%, the N-(3-methoxy4-hydroxy-phenethyl-p-benzyloxyphenylacetamide from this latter, by cyclization according to Bischler-Napieralski with phosphorus oxychloride in acetonitrile, followed by reduction with sodium borohydride, there is obtained with a yield of 75% to 80% the 1-(p-benzyloxybenzyl)-6-meth-oxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline, which is methylated with formaldehyde and formic acid giving 1 (p-benzyloxybenzyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydro-isoquinoline with a yieid of 90%. 

With the simpler 1-benzyl derivatives (those which have not undergone any ortho-attack), the removal of the 1,2-bond usually produces a 2-styryl substituted phenethylamine. Again, this would be located in the entry that described the parent isoquinoline. 

The second illustration above is a phthalide THIQ, and these phenethylamines are sometimes referred to as secophthalide-isoquinolines. Here, the oxygen atom of the original isofuranone ring is substituted on the newly formed double bond. This structure can easily open up to the corresponding ketonic carboxylic acid. These seco-modifications of the attacked isoquinoline (first example, illustrated with an aporphine) and the simpler 1-substituted isoquinolines (second example, as illustrated by the isobenzofuranone) are the only ones included in this book. The standard phenethylamines that are commonly found in cacti, compounds which are not from these seco-mecha-nisms, have been tabulated in TIHKAL and will not be repeated here. 

Of the alkaloids so far identified in just L. william-sii alone, 15 are Beta-phenethylamine and simple isoquinoline alkaloids. Mescaline, N-methylmescaline, N-acetylemescaline, anhalamine, anhalonine, anhalidine, anhalinine, anhalonidine, lophophorine, O-methylan-halondedine, and pellotine have all been identified as the principal components of the plant. However, only mescaline has so far been determined to cause hallucinations. 

Alkaloid synthesis from yic-tricarbonyl compounds. Wasserman s group1 has used the strongly electrophilic character of the central carbonyl of a Wc-tricarbonyl system for synthesis of several alkaloids. Thus several isoquinoline alkaloids can be prepared by reaction of a phenethylamine with the tricarbonyl 1. 

The Pd-catalyzed cyclization of appropriate 2-phenethylamine derivatives is a commonly used approach to the isoquinoline system as illustrated by Scheme 111 <2002JOC465, CHEC-III(7.05.2.1)234>. 

The Pictet-Spengler cyclization proceeds in vitro as in Fig. 2, which shows a hypothetical example in the isoquinoline series, via several distinct intermediates which cannot be isolated in the laboratory (6c, I Ob). Addition of acetaldehyde to a phenethylamine activated by a phenolic hydroxy group first affords a carbinolamine, which, under the influence of acid, dehydrates to a Schiff base that is most likely present as the more stable E isomer, affording on protonation directly the racemic tetrahydro-isoquinoline [( )-TIQ] (I0a,b). In attempting to explain the formation of optically active mammalian isoquinolines in vivo, we cannot disregard the possibility that the phenolic group of the phenethylamine substituent is... 

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... 

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