5-Methoxyindole-3-acetic acid

Merour, J.Y., Coadou, J.Y., and Tatibouet, E, Syntheses of 2(5)-substituted l-acetyl-3-oxo-2,3-dihy-droindoles, 3-acetoxy-l-acetylindoles, and of 2-methyl-5-methoxyindole-3-acetic acid. Synthesis, 1053, 1982. 

The Determination of 5-Methoxyindole-3-acetic Acid in Human Urine by Mass Fragmentography J. Chromatogr. 145(2) 285-289 (1978) CA 88 185621m... 

C11H11NO3, 5-Methoxyindole-3-acetic acid, 41B, 322 C11H12N2, 6-Dimethylamino-5-aza-azulene, 34B, 149 C11H12N2O3, 5-Hydroxy-DL-tryptophan, 39B, 197... 

C22H20CI4N2O2, N,N,N ,N -Tetramethylbenzidine - chloranil, 39B, 452 C22H20N4, Tetracyanobenzene - hexamethylbenzene, 33B, 250 C22H20N6 f 7,7,8,8-Tetracyanoquinodimethan-N,N,N ,N -tetramethyl-p-phenylenediamine complex, 30B, 249 C22H25N3O4, 5-Methoxyindole-3-acetic acid - 5-methoxytryptamine,... 

M is synthesized from serotonin by acetylation to A-acetyl rotonin, followed by methylation (catalysed by acetylserotonin methyltransferase, EC 2.1.1.4) to M.In the pineal gland M. biosynthesisis is controlled by epinephrine, which stimulates adenylate t clase (EC 4.6.1.1), which in turn stimulates protein kinase. The first three steps of M. synthesis (L-tryptophan S-hydroxytryptophan -> serotonin - A-acetyl-5-hydroxytryptamine) are promoted in this way, but the methyltransferase is not affected. However, the rate-limiting step is catalysed by serotonin A-acetyltransferase. M. is inactivated and excreted as 6-hydroxymelatonin, or as 5-methoxyindole-acetic acid. 

A mixture of 9.5 g pyrrolyl-2-aldehyde, 29.2 g dimethyl-succinate and NaH (9.6 g of 50% suspension in oil) in 100 ml benzene is stirred at room temperature 6 hours, cooled and carefully acidified with glacial acetic acid. Add water and ether and dry, evaporate in vacuum or work up (JACS 72,501 (1950), JCS 1025(1959)) to get ca. 17 g (80%) 3-methoxycarbonyl-4-(2 -pyrrolyl)-3-butenoic acid (I) (recrystallize-acetone-benzene). A mixture of 12 g (I), 7 g sodium acetate and 70 ml acetic anhydride is left overnight at room temperature with occasional shaking. Then gradually raise the temperature to 70-75° over 2 hours, maintain for 4 hours and work up (see JCS 1714(1955), 986( 1958)) to get ca. 8 g (60%) methyl-4-acetoxy-indole-6-carboxylate (II) (recrystallize-petroleum ether). If desired, this can be converted to 4-OH-indole-6-COOH and 4-methoxyindole-COOH as described in the ref. or decarboxylated as described elsewhere here. If the 1-methyl cpd. is used, 1-Me-indole results. 

Methyl 5-methoxyindole-2-acetate lndole-2-acetic acid, 5-methoxy-, methyl ester (8) 1H-lndole-2-acetic acid, 5-methoxy-, methyl ester (9) (27798-66-9) 5-Methoxy-2-nitrophenylacetic acid Acetic acid, (5-methoxy-2-nitrophenyl)- (8) Benzeneacetic acid, 5-methoxy-2-nitro- (9) (20876-29-3)... 

The next three procedures provide useful synthetic intermediates. A stereospecific synthesis of ETHYL (Z)-3-BROMO-2-PROPENOATE affords an alternative vinyl bromide partner for the coupling chemistry in the preceding procedure. A very simple but elegant illustration of the flash vacuum pyrolysis technique is used to prepare BENZOCYCLOBUTENONE from o-toluoyl chloride. Another member of the functionalized indole family of synthetic intermediates is presented in a four-step procedure for 5-METHOXYINDOLE-2-ACETIC ACID METHYL ESTER. 

Teuber and Schmitt hydrogenated 5-methoxyindole over ruthenium dioxide in 90% ethanol at elevated temperature and pressure and obtained the corresponding octahy-droindole in a 79% yield (eq. 12.9).11 The hydrogenation was difficult to complete with platinum or rhodium-platinum as catalyst in acetic acid. 

Monoterpene Bases.—Yohimbine-Corynantheine (and Related Oxindoles)-Pier aline Group. It is well known that 3,4-dehydroyohimbane (35a) is reduced by zinc-acetic acid to a mixture of yohimbane (35c) and i/ -yohimbane (35d) however, when 10-methoxy-3,4-dehydroyohimbane (35b) was similarly treated, a 2,3,4,7-tetrahydro-derivative (17 % yield) was formed as well as the corresponding 10-methoxy-yohimbanes. It was shown that this did not arise by further reduction of either of the methoxy-yohimbanes and no explanation is yet available for this interesting difference. Reserpine, a 6-methoxyindole, underwent C(3)-N(4) bond fission on reaction with zinc-acetic acid, as did indoles with no ring A methoxy-group. Cleavage of the C(3)-N(4) bond with the formation of N(4)-cyano-C(3)-alkoxy- or hydroxy-seco-derivatives was observed when yohimbine, i/ -yohimbine, and methyl reserpate were subjected to von Braun degradation conditions in alcohol or aqueous solution. 

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