4- Hydroxyphenethylamine

EXTENSIONS AND COMMENTARY The rationale for exploring the beta-hydroxylated phenethylamines, especially those with oxygens at the biologically important 3- and 4-positions, has already been presented. Norepinephrine is a 6-hydroxylated phenethylamine with oxygens at these two ring positions. With DME, these are masked as two methyl ethers, and the initials DME stand for 3,4-dimethoxyphenyl-B-ethanolamine. This is an alternate name for 3,4-dimethoxy-B-hydroxyphenethylamine. 

Tyramine, hordenine, 3,4-dimethoxy-j8-phenethylamine, jV-methyl-3,4-dimethoxy-j3-hydroxyphenethylamine (86 amorphous a new natural base), salsoline, salsolidine, tryptamine, abrine, and hypa-phorine (54). 

Analytical Properties Separation of primary a-amino alcohols, for example, p-hydroxyphenethylamines and... 

Chloro-3,4-dimethoxyphenethylamine (1.0 g) was reacted with 0.70 g of p-methoxystyrene oxide to give the hydroxyphenethylamine m.p. 118.5-121°C. This compound (2.16 g) was stirred at room temperature in 15 ml of trifluoroacetic acid with 4 drops of cone, sulfuric acid. After purification over a silica gel column with chloroform, 10% methanol/chloroform as eluates, was obtained 6-chloro-7,8-dimethoxy-l-p-methoxyphenyl-2,3,4,5-tetrahydro-lH-... 

The thermal condensation of p-benzyloxyphenylacetic acid and of 3-methoxy-4-hydroxyphenethylamine occurs and gives, with a yield of 86% to 92%, the N-(3-methoxy-4-hydroxyphenethyl-p-benzyloxyphenyl)acetamide 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 l-(p-benzyloxybenzyl)-6-methoxy-7-hydroxy-l,2,3,4-tetrahydroisoquinoline, which is methylated with... 

Three chiral stationary phases that were prepared by derivatizing y-mercaptopropylsilanized silica gel with quinine (CSP II), quinidine (CSP III), and cinchonidine (CSP IV), have been used for the successful resolution of N-acyl derivatives of fl-hydroxyphenethylamines [25]. UV and CD detectors set at 270 nm were used in series. The effectiveness of the separation and the detection are illustrated in Figure 6 for the resolution of the N-(3,5-dinitrobenzoyl) derivative of phenylethanolamine on CSP III. 

The biosynthetic work on mescaline in the peyote cactus L. williamsii and in the Peruvian cactus T. pachanoi has led to the formulation of biosynthetic pathways according to Scheme 2. A major pathway probably involves decarboxylation of tyrosine followed by hydroxylation to yield dopamine. Dopamine is methylated on the meta hydroxy group to 4-hydroxy-3-methoxyphenethylamine (3-methoxytyramine) which then undergoes hydroxylation to the key intermediate 4,5-dihydroxy-3-methoxyphenethylamine (20). Para-O-methylation of 20 yields 3,4-dimethoxy-5-hydroxyphenethylamine (21), which is the immediate precursor of the main phenolic tetrahydroisoquinolines of peyote. Alternatively, meta-O-methylation yields 3,5-dimethoxy-4-hydroxyphenethylamine (19), which is further efficiently methylated to mescaline. Parallel pathways involving N-methylated compounds probably exist in these cacti (10). 

PictetGams preparation of isoquinolines from iV-acylated 2-hydroxyphenethylamines, e.g., the synthesis of papaverine 180 (Scheme 107), utilizes similar conditions. 

Disposition in the Body. Readily absorbed after oral administration. It is concentrated in the kidneys, liver, and spleen. About 90% of a dose is excreted in the urine in 24 hours with about 30% as 3,4,5-trimethoxyphenylacetic acid, which is inactive the remainder is mostly unchanged drug, together with 3,4-dihydroxy-5-methoxyphenylacetic acid which is excreted as a glutamine conjugate. Other metabolites include V-acetylmesca-line and V-acetyl-3,4-dime thoxy-5-hydroxyphenethylamine. 

A synthetic route to ( )-0,f>-dimethyltubocurarine iodide (CXXV), via the racemate of 0,0-dimethylbebeerine (CXXIII), was announced in 1959 by Tolkachev and his collaborators (94). It started by the condensation of 3-methoxy-4-hydroxyphenethylamine with 4-benzyloxy-phenylacetic acid to give the amide CXXVI. Reaction of the potassium salt of the latter with the methyl ester of 3-bromo-4-methoxyphenyl-acetic acid in the presence of copper powder gave compound CXXVII. This on condensation with 3-methoxy-4-hydroxy-5-bromophenethyl-amine afforded compound CXXVIII, which was methylated to CXXIX. The latter compound was cyclized with phosphorous oxychloride to the dihydroisoquinoline derivative CXXX. Debenzylation of CXXX followed by intramolecular Ullmann condensation yielded compound CXXXI. The latter was converted to racemic dimethylbebeerine (CXXIII) by reduction with zinc dust in acetic acid followed by methyla-tion. Finally, treatment of ( + )-CXXIII with methyl iodide furnished the dimethyl ether of ( + )-tubocurarine iodide, identified by comparison of its UV-spectrum with that of the dimethyl ether of natural tubo-curarine iodide and by melting-point determination of a mixture of the two specimens. 

The j3-hydroxyphenethylamine synephrine (198) appears to arise in Citrus from tyrosine via tyramine and iV-methyltyramine. ° Normacromerine (199) and macromerine (200) are found in the cactus Coryphantha macromeris var. runyoniO Their genesis has also been studied.Specific incorporations of DL-[3- C]tyrosine, [l- C]tyramine, DL-[2- " C]dopa, and [l- CJdopamine into normacromerine established a pattern of biosynthesis similar to that of the other cactus alkaloids and again a C6-C2 unit is implicated. [This contrasts with the biosynthesis of the superficially similar base ephedrine (185), discussed above.]... 

Tyramine (p-hydroxyphenethylamine) was isolated in 1909 by Barger and Dale (176) from Claviceps purpurea (ergot) and also by Henze (184) from the salivary gland of cephalopods. It provokes a salivary secretion, a contraction of the piloerectors, a mydriasis, and a slowing of the pulse rate in the dog (185). In the cat (0.06 g. subcutaneously) there can be noted, in addition, a motor stimulation, a respiratory excitation, and a hyperthermia (186), and in rats there is an increase in the respiratory volume (0.01-0.1 g. subcutaneously (187)). Bry (173) confirms the respiratory stimulation which tyramine provokes. 

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