The amino groups of pseudomycin B (I) were protected by treatment with N-(benzyloxycarbonyloxy)succinimide (II). The resulting pseudomycin B tribenzyl carbamate (III) was then coupled with cyclopropylamine (IV) by using TBTU to yield amide (V).
The N-benzyloxycarbonyl protecting groups of (V) were finally removed by catalytic hydrogenation over Pd/C.
In a closely related method, pseudomycin B (I) was protected as the corresponding allyl carbamate (VII) by treatment with diallyl pyrocarbonate (VI). After coupling of (VII) with cyclopropylamine (IV), the allyloxycarbonyl groups were deprotected by means of tributyltin hydride and palladium chloride.
The acylating reagent (V) was prepared as follows. Allylic bromination of 4,5-dimethyl-1,3-dioxolene-2-one (I) with N-bromosuccinimide afforded bromide (II). This was converted to alcohol (IV) via formation of the formate ester (III), followed by acidic hydrolysis. Reaction of (IV) with p-nitrophenyl chloroformate and pyridine furnished carbonate (V). The acylation of pseudomycin B (VI) with carbonate (V) produced a mixture of mono-, di- and triacylated compounds from which the desired tricarbamate was isolated by reverse-phase preparative HPLC.
Acylation of pseudomycin B (I) with the succinimidyl ester (III), prepared from chloroformate (II), produced a mixture of mono-, di- and tri-N-acylated compounds, which were separated by means of HPLC. The required trisubstituted compound (IV) was then condensed with cyclopropylamine (V) in the presence of TBTU to afford the title amide.