TUMOUR CHEMOTHERAPY ⅩⅩⅩⅥ SYNTHESIS OF DL-N-DICHLOROACETYI-5-NITROTRYPTOPHAN AND RELATED COMPOUNDS

In the present work, the compounds DL-N-dichloroacetyl-5-nitrotryptophan (I_c), DL-5-nitro-tryptophan hydrochloride (Ⅱ_c) and their ethyl esters (Ⅰ_d and Ⅱ_d) were prepared and found to be less effective against Hela cells than their corresponding 7-nitro analogs (Ⅰ).5-Nitrogramine (Ⅴ) was condensed with diethyl formamidomalonate and dimethyl sulphate in the presence of sodium alcoholate, affording diethyl α-formamido-α-(5-nitroindolyl methyl)-malonate (Ⅵ). The latter was hydrolyzed in concentrated hydrochloric acid to give 5-nitrotryptophan hydrochloride(Ⅱ_c), from which the desired product, DL-N-dichloroacetyl-5-nitrotryptopban (Ⅰ_c), was obtained by acylation with dichloroacetylchloride in dilute sodium hydroxide. The ethyl ester of DL-5-nitrotryptophan (Ⅱ_d) was obtained by esterification of Ⅱ_c with absolute ethyl alcohol saturated with gaseous hydrogen chloride and was then treated with dichloroacetyl-chloride in the presence of aqueous sodium acetate or in boiling benzene.