Methyl anthranilic acid

A-Methyl anthranilic acid (2) as supplied by Aldrich (Cat. 13,706-5) contains 5% anthranilic acid (1) and must be purified by recrystallization from EtOH before use. The remaining anthranilic acids were used as received from Aldrich. 

Evodia rutaecarpa (Juss.) Berth Wu Zhu Yu (Evodia) (fruit) Alkyl methyl quinolone alkaloids, evodiamine, limonin, evocarpine, rutaecarpine, N-methyl anthranilic acid, evodol, hydroxyevodiamine, N-methylanthranflamide, N,N-dimethyl-5 -methoxytryptamine, dehydroevodiamine.32,33,237 Antiemetic, analgesic, lower blood pressure, antibacterial. 

Reagents were obtained from commercial sources and used as received. V-Boc anthranilic acid 13 was purchased from Advanced Chem-Tech and V-Boc-methyl anthranilic acid 14 was purchased from Aldrich. Proton nuclear magnetic resonance ( H NMR) spectra were run at 500 MHz. LC/MS analysis was performed using a Ci8 Hypersil BDS 3-prn 2.1 x 50-mm column (UV 220 nm) with a mobile phase of 0.1% TFA in CH3CN/H20, gradient from 10% CH3CN to 100% over 5 or 15 min and APcI ionization. 

The anthranilic acid may also be converted into phenyl glycine ortho-carboxylic acid by the action of formaldehyde and potassium cyanide, yielding first cyano-methyl anthranilic acid which on hydrolysis is converted into the phenyl glycine compound. 

The ester is obtained in 97 per cent, yield by adding the methyl ester of methyl anthranilic acid to mercuric acetate solution in methyl alcohol, the reaction being complete in about thirty minutes. It forms fine needles, M.pt. 200° C., easily soluble in chloroform, hot acetic acid, boiling alcohols, ethyl acetate, acetone, or benzol, slightly soluble in cold water. 

C]Tryptophan gave inactive alkaloids but tritiated 2,4-dihydroxy-quinoline (34) and its N-methyl derivative were incorporated into (47) (0.009 % and 0.020% respectively) an early route had suggested the derivation of what was essentially (34) from tryptophan. Radioisotope dilution showed the presence of both these quinoline precursors together with iV-acetyl- and N-methyl-anthranilic acid in A. baueri. A satisfactory incorporation of N-methylanthranilic acid into (47) was found in Evodia xanthoxyloides, and this, together with its natural occurrence, indicates that early methylation may be important in the biosynthesis of acridone alkaloids. 

HA is specifically methylated to form 3-hydroxy-4-methyl-anthranilic acid [180-181]. This reaction is catalysed, in Streptomyces antibioticus, by a specific methyltransferase [182]. The enzyme appears to be bound to cell membrane, and is rather specific for example, HK is a non-substrate. 

Amino-2-hydroxy[4- C]butyric acid (the corresponding aldehyde has been condensed with o-aminobenzaldehyde to give vasicine 4-hydroxy-[2- C]glutamic acid (found with vasicine in Linaria yw/garis ), N-methyl-anthranilic acid, and N-formylanthranilic acid have been tested as vasicine precursors in A. vasica, without success. 

H-nmr 5 2.53 (3H, s, NMe) and 5.90 (IH, s, C3-H). The structure of (67) was partially revealed by alkaline hydrolysis which yields N-methyl-anthranilic acid and 3,4-dihydro-p-carboline. Boiling alcoholic potassium hydroxide degrades (67) to N-methylanthranilic acid, carbon dioxide and tryptamine. When boiled with alcoholic hydrochloric acid (67) yields optically inactive isoevodiamine [evodiamine hydrate (74)] which can be recyclized with acetic anhydride or oxalic acid to optically inactive evodiamine. (67) can be converted to rutaecarpine via the dry hydrochloride of (74), which, on heating, yields (63). The chemistry of evodiamine has been reviewed by Armarego (6) see also (25, 94, 134, 169). 

Evodiamine (16) is an indoloquinazoline alkaloid of mixed biosynthetic origin and possesses three nitrogen atoms arising from tryptophan and Af-methyl-anthranilic acid residues [78]. It is chief alkaloid from fruits of Evodia rutaecarpa Bentham (Rutaceae), a plant widely used by traditional Chinese medicine [79]. 

The corresponding imine with methyl anthranilic acid (Verdantiol) showing an odor of orange and linden blossom is used as a fixative. See Ref. [26]. 

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