Synthesis of TR Analogs for Cancer Research

TR is structurally identical to the known anti-cancer drug; actinomycin, except in the valine motif and additional oxygen (Fig 1). Synthesis of TR analogs was carried out by following the methods as described elsewhere for the synthesis of actinomycin drug analogs [9 (link)–12 (link)]. Analogs of the parent compound were synthesized by deactivation of NH₂ group by N-substitution via chemical modification and deactivation of the keto group by chemical reduction methods.
Analogs of TR namely, TR-NC6, Tr-SUND, TRR, TR-RB, FN-Me, and C-tertbutyl were synthesized. TR-NC6 was synthesized by N-Alkylation of TR using 4-Hydroxy (hexyl)-Coumarin. Tr-SUND was derived by N-Glycosylation of TR using Acetobromo-α-D-Glucose. TRR was prepared by sodium borohydride (NaBH₄) mediated reduction of TR’s keto group. Benzoylation of the TR OH group using 4-Methoxy-Benzoyl Chloride resulted in the TR-RB. N-Alkylation of TR using Iodomethane was done to synthesize FN-Me and Bromination-alkylation of TR using 3,5-Ditert-buty-4-hydroxybenzoic acid methyl ester was used to prepare C-terbutyl-TR (S14 Fig in S1 File).