Synthesis of Novel Tryptophan Derivatives of Potential Biological Activity

Abstract

Tryptophan methyl ester 2 reacts with ethyl cyanoacetate to form acetonitrilocarbonyltryptophan methylester 3. The latter reacts with cyanomethylene reagents, hydrazines, cyanomethylenes and sulfur to form the corresponding α-pyrido-3-indolopropanoate derivatives 6a,b, pyrazolyltryptophan methyl ester derivatives 8a,b and thiophenotryptophan methyl ester derivatives 10a,b, respectively. Also compound 3 reacts with benzaldehyde to give the condensated product 12. The reactivity of the latter product towards chemical reagents was studied to form pyridine, pyrazole and isoxazole derivatives.

Recent Developments in the Synthesis of Indole‐Pyrazole Hybrids

“…[54] The cyclocondensation of bis-heterylmonothio-1,3-diketones (104) with arylhydrazines in EtOH under reflux conditions selectively formed the pyrazole C3regioisomer (105) as shown by Method I. The other regioisomer in which the indole moiety connected to the C5-position of pyrazole (107) was obtained by the treatment of 3-acetylpyridine (102 a) and 2-acetylfuran (102 b) with indolyl-dithioester (103) followed by in situ methyl iodide-mediated methylation and cyclocondensation with arylhydrazines in tert-butanol ( t BuOH) in the presence of potassium tert-butoxide (Method II). A one-pot three-component reaction was also established for the preparation of compound 107 with high regioselectivity (Scheme 16).…”

“…Ethanamine‐linked regioisomeric indole‐C3 pyrazole hybrids ( 308 & 310 ) have been synthesized starting from tryptophan by Mohareb and co‐workers as shown in Scheme 54 [107] . Tryptophan methyl ester ( 306 ), which was obtained by the reaction of tryptophan with acetyl chloride, afforded the intermediate 307 in 75 % yield upon treatment with ethyl cyanoacetate in refluxing 1,4‐dioxane.…”

“…Ethanamine-linked regioisomeric indole-C3 pyrazole hybrids (308 & 310) have been synthesized starting from tryptophan by Mohareb and co-workers as shown in Scheme 54. [107] Tryptophan methyl ester (306), which was obtained by the reaction of tryptophan with acetyl chloride, afforded the intermediate 307 in 75 % yield upon treatment with ethyl cyanoacetate in refluxing 1,4-dioxane. Compound 307 on cyclization with hydrazine hydrate and phenyl hydrazine in EtOH in the presence of TEA afforded the hybrid molecules (308) in which the indole-C3 was linked to the pyrazole-C5 by ethanamine.…”

Development of new indole-derived neuroprotective agents

“…The starting compound a-amino(acetonitrilocarbamido)-3-indolopropionic acid (15) was prepared according to the published procedure. 19 …”

“…19 The reactivity of acetonitrile moiety of compound 15 towards the formation of tetrazole ring was studied. In attempts of having a straightforward synthesis of indolyl tetrazolopropanoic acid, the reaction of compound 15 with sodium azide 16 in dimethylformamide containing a catalytic amount of ammonium chloride has been carried out.…”