1- Methyl-3-indolylacetic acid

The o-nitrobenzenesulfenamide has been used for the protection of amino acids. o-Nitrobenzenesulfenamides, B, are also cleaved by acidic hydrolysis (HCl/Et20 or EtOH, 0°, 1 h, 95% yield)" by nucleophiles (13 reagents, 5 min-12 h, 90% cleaved) by PhSH or HSCH2CO2H, 22°, 1 h by 2-mercaptopyri-dine/CH2Cl2, 1 min, 100% yield) by NH4SCN, 2-methyl-1-indolylacetic acid and by catalytic desulfurization (Raney Ni/DMF, column, a few hours, satisfactory yield). 

A) 2-Methyl-5-Methoxy-3-lndolylacetic Anhydride Dicyclohexylcarbodiimide (10 g, 0.049 mol) is dissolved in a solution of 2-methyl-5-methoxy-3-indolylacetic acid (22 g, 0.10 mol) in 200 ml of THF, and the solution Is allowed to stand at room temperature for 2 hours. The precipitated urea is removed by filtration, and the filtrate is evaporated in vacuo to a residue and flushed with Skellysolve B. The residual oily anhydride is used without purification in the next step. 

In order to study how a silatrane group which is present in phytohormones influences their activity we have investigated the action of silatranylmethyl esters of 2-methyl-phenoxyacetic, 4-chlorophenoxyacetic and 3-indolylacetic acids on the suspended cul-... 

D) 1 -p-Chlorobenzoyl-2-Methyl-5-Methoxy-3-Indolylacetic Acid A mixture of 1 g ester and 0.1 g powdered porous plate is heated in an oil bath at 210°C with magnetic stirring under a blanket of nitrogen for about 2 hours. No intensification of color (pale yellow) occurs during this period. After cooling under nitrogen, the product is dissolved in benzene and ether, filtered, and extracted with bicarbonate. The aqueous solution is filtered with suction to remove ether, neutralized with acetic acid, and then acidified weakly with dilute hydrochloric acid. The crude product (0.4 g, 47%) is recrystallized from aqueous ethanol and dried in vacuo at 65°C MP 151°C. 

Preparation of l-(p-nitrobenzoyl)-5-methoxy-2-methyl-3-indolylacetic acid ... 

Scheme 25 summarises the molecular ions to be expected from thermal inter-molecular transmethylation of a tertiary N(b>-atom. Such reactions have been investigated with simple model compounds. In the realm of bisindole alkaloids they were first observed with voacamine and vinblastine types. With the help of deuterium labelling it has been shown in the case of voacamine (141) (Section 9, p. 242) that the methyl group of the a-indolylacetic acid methyl ester function of the Iboga component is transferred to the N(b)-atom of the vobasinol component. An a-indolylacetic acid methyl ester is also present in the Vinca bisindole alkaloids (Section 10). It seems probable that the methyl transfer takes place in concert with decarboxylation to give the anion (290). The other methoxycarbonyl group is apparently not involved in methyl transfer. 

The majority of bisindole alkaloids which possess methoxycarbonyl groupings, other than of the above-mentioned type, e.g. villalstonine (213), pycnanthine (193), and vobtusine (255), show no significant methyl transfer in the mass spectrometer. An exception is umbellamine (235) (Section 13, p. 279). The occurrence of such reactions can be minimised by dispersion of the sample on glass powder before vaporisation, thus facilitating determination of the true molecular weight. The latter may be confirmed in the case of a-indolylacetic acid methyl ester derivatives by examination of reduction or demethoxycarbonylation products. 

The effectiveness of this protocol was demonstrated by tbe first catalytic asymmetric synthesis of the (+)-a-methyl-3-indolylacetic acid fragment of acremoauxin A, a potent plant growth inhibitor (eq 8). 

To a solution of 23.3 g (0.1 mole) of methyl-5-methoxy-2-methyl-3-indolylacetate in 50 ml of dry toluene are added 3 g of 80% sodium hydride. The mixture is stirred at room temperature for 4 hours and then a solution of 18.56 g (0.1 mole) of p-nitrobenzoylchloride in 80 ml of dry toluene is added slowly thereto over a 30-minute period. The reaction mixture is boiled for 30 hours. After cooling it is poured into 400 ml of ice-water and 15 ml of acetic acid. The separated toluene solution is washed with a large quantity of water, dried over sodium sulfate and evaporated to a syrup which is dissolved in ether. Slow evaporation of this solution in an open beaker gives 10 g of methyl-l-(p-nitrobenzoyl)-5-methoxy-2-methyl-3-indolylacetate as yellow prisms. Another quantity may be recovered from the oily residue after chromatography on a silica gel column (elution with benzene). MP 134-135°C (crystallization from MeOH). 

A solution of 4.9 g (12.8 mmol) of methyl-l-(p-nitrobenzoyl)-5-methoxy-2-methyl-3-indolylacetate in 40 ml of acetic acid containing 400 mg of p-toluene-sulfonic acid is refluxed for 20 hours and then concentrated in vacuum. The gummy residue is extracted with ethyl acetate. The extract is filtered from insoluble material, washed with water and dried over sodium sulfate. Removal of the solvent under reduced pressure affords the desired product as yellow crystals MP 185-186°C. 

A procedure has been established for the synthesis of certain aspidospermine alkaloids, based on the addition of an enolate of methyl 2-indolylacetate to a pyridinium salt (367), followed by acid-catalyzed cyclization of the resulting 1,4-dihydropyridine (368) to the tetracyclic structure (369) (Scheme 124) <84H(21)325,89J0C1166,94T5233>. 

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