Condensation of the secondary amine (I) with N5-Boc-N2-Z-ornithine (II) using EDC provided the acetal amide (III), and subsequent acid-catalyzed intramolecular cyclization of (III) in hot toluene gave rise to the pyrazinone (IV). Catalytic hydrogenation of the double bond with concomitant hydrogenolysis of the benzyloxycarbonyl group of (IV) provided the 1,3-substituted-2-oxopiperazine (V). This was condensed with Z-glycine (VI) to give amide (VII). Then, acid cleavage of the tert-butyl ester and N-Boc protecting groups of (VII) provided (VIII). The N-benzyloxycarbonyl group of (VIII) was subsequently removed by hydrogenolysis, yielding diamine (IX). Finally, acylation of (IX) with the imido ester of 4-guanidinobenzoic acid (X) furnished the title bis(4-guanidinobenzamide).

Condensation of the secondary amine (I) with N5-Boc-N2-Z-ornithine (II) using EDC provided the acetal amide (III), and subsequent acid-catalyzed intramolecular cyclization of (III) in hot toluene gave rise to the pyrazinone (IV). Catalytic hydrogenation of the double bond with concomitant hydrogenolysis of the benzyloxycarbonyl group of (IV) provided the 1,3-substituted-2-oxopiperazine (V). This was condensed with Z-glycine (VI) to give amide (VII). Then, acid cleavage of the tert-butyl ester and N-Boc protecting groups of (VII) provided (VIII). The N-benzyloxycarbonyl group of (VIII) was subsequently removed by hydrogenolysis, yielding diamine (IX). Finally, acylation of (IX) with the imido ester of 4-guanidinobenzoic acid (X) furnished the title bis(4-guanidinobenzamide).