Trimethoxyphenylacetic acid

The fourth modification is the compound with the nitrogen atom oxidatively removed from the scene. This is the mescaline metabolite, 3,4,5-trimethoxyphenylacetic acid, or TMPEA. Human dosages up to 750 milligrams orally failed to produce either physiological or psychological changes. 

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. 

The combretastatins are a group of antimitotic agents isolated from the bark of the South African tree Combretum caffrum. A novel and highly stereoselective total synthesis of both the c/s and trans isomers of combretastatin A-4 was developed by J.A. Hadfield and co-workers.The (Z)-stereoisomer was prepared using the Perkin reaction as the key step in which 3,4,5-trimethoxyphenylacetic acid and 3-hydroxy-4-methoxbenzaldehyde was heated with triethylamine and acetic anhydride at reflux for several hours. The a,p-unsaturated acid was isolated in good yield after acidification and had the expected ( ) stereochemistry. Decarboxylation of this acid was effected by heating it with copper powder in quinoline to afford the natural product (Z)-combretastatin A-4. 

The last compound, alpha-D, could be quite a different matter. The principal metabolite of mescaline is 3,4,5-trimethoxyphenylacetic acid, and this product requires enzymatic attack at the exact position where the deuteriums will be located. To the extent that they are harder to remove (come off more slowly or to a lesser degree), to that extent the molecule will be more potent in man, and the dosage required for effects will be less. The compound will be easily made by the reduction of 3,4,5-trimethoxyphenylacetonitrile with lithium aluminum deuteride. 

A mixture of 0.67 g 3-hydroxy-4-methoxybenzaldehyde (4.4 mmol), 2.0 g 3,4,5-trimethoxyphenylacetic acid (8.84 mmol), 4 mL acetic anhydride, and 2 mL triethylamine was refluxed for 3 h. After acidification with 6 mL cone. HCl, the resulting solid was filtered off and recrystalUzed from ethanol to give 950 mg -2-(3, 4, 5 -trimethoxyphenyl)-3-(3 -hydroxy-4 -methoxyphenyl)prop-2-enoic acid as fine yellow needles, in a yield of 60%, m.p., 237-239°C. 

Four furans (2-fiiraldehyde, 2-acetyl fiiran, 2-methyl furan, 5-(hydroxymethyl)-2-furfural) and nine phenolics (e.g., gallic acid, 3,4,5-trimethoxyphenylacetic acid, vanillin, coniferaldehyde) were extracted fiom distilled spirits (whiskey,... 

According to Slotta and Muller, mezcaline is excreted in urine in the form of trimethoxyphenylacetic acid. ... 

Raymond-Hamet (169, 170) found that small doses of mescaline do not have any effect on the blood pressure of dogs while larger ones (20 mg./kg.) caused hypotension. Mescaline is antagonistic to the pressor action of adrenaline and the subsequent vagal effect. Slotta and Muller (121) observed that 40 to 50% of the mescaline fed to rabbits is excreted in form of trimethoxyphenylacetic acid the latter is not found in human urine after the administration of mescaline. According to Richter (171) mescaline is excreted by humans unchanged, at least to a high extent (recovery, 58%). Bemheim and Bernheim (172) studied the mecha-... 

Also obtained by reaction of resorcinol with homoasaronic acid (2,4,5-trimethoxyphenylacetic acid) (m.p. 102-103°),... 

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