5-Hydroxyindole-3-acetamide

Initially the modifier consisted of indole propionic acid dissolved in water at a concentration of 1 mM. Increasing the concentration of indole propionic acid up to the limit of its solubility increases the initial activity of the modified RNase. The use of modifiers such as 5-hydroxyindole-3-acetic acid and 5-hydroxyindole-3-acetamide, which are more water soluble than indole propionic acid, increased the activity even further. 

Several literature studies indicate that the mechanism of crosslinking proteins with glutaraldehyde changes dramatically with the pH of the reaction.0 2 Using 5-hydroxyindole-3-acetamide as the modifier (10 mM) and perturbation at pH 3.0, several samples of RNase were crosslinked in the pH range of 3 to 8. The highest activity is obtained when RNase is crosslinked at pH 3 to 4, the same pH used for perturbation. 

The cyclization of IV-allyl-o-haloanilines was adapted to the solid phase for both indoles [332, 333] and oxindoles [334]. For example, as illustrated below, a library of l-acyl-3-aIkyl-6-hydroxyindoles is readily assembled from acid chlorides, allylic bromides, and 4-bromo-3-nitroanisole [332], Zhang and Maryanoff used the Rink amide resin to prepare Af-benzylindole-3-acetamides and related indoles via Heck cyclization [333], and Balasubramanian employed this technology to the synthesis of oxindoles via the palladium cyclization of o-iodo-N-acryloylanilines [334], This latter cyclization route to oxindoles is presented later in this section. 

Reduction of 46b with EtsSiH/TFA produces similarly N-methyl-bis-2,3-dihydroindole (47b, 85%). Employing the tungstate method, 47a,b and 48 are converted to N-[2-(l-hydroxyindol-3-yl)ethyl]-l-hydroxyindole-3-acet-amides (49a, 51% 49b, 39%) and N-[2-(l-hydroxyindol-3-yl)ethyl]indole-3-acetamide (50, 55%), respectively. Subsequent methylation of 49a,b and 50 affords 43a (91%), 43b (72%), and 51 (100%). 

To an oven-dried Schlenk tube was added phosphoric acid (S)-125 (7.5 mg, 0.01 mmol), 4-hydroxyindole 136 (0.14 mmol), iV-(l-phenylvinyl)acetamide (enamide 143, Ar = Ph, 0.1 mmol), and 90 mg 4 A molecular sieves. The mixture was degassed, placed under a N2 atmosphere dissolved in toluene (1.5 mL) and stirred at RT until TLC indicated reaction completion. The solvent was removed under vacuum and the residue purified by flash colunm chromatography on silica gel (eluted with 1 1 ethyl acetate/petroleum ether to afford the (i -adduct 144 (R = 4-OH) in 95% yield and 86% ee m.p. 107-110 °C [o]d = -62.3 (c 0.7, acetone). 

V-(Diphenylmethylene)acetamide, in D-60482 6-Hydroxyindole Benzyl ether, in H-60158 Phthalimidine V-Benzyl, in P-70100... 

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