Daptomycin (I) was obtained as a fermentation product from Streptomyces roseosporus. Selective acylation of (I) at the lysine side-chain amino group by means of N-Boc-tryptophan activated as either the pentafluorophenyl (II) or the p-nitrophenyl ester (III) furnished the corresponding tryptophan amide (IV).
The N-Boc group of (IV) was then removed by treatment with trifluoroacetic acid in the presence of thioanisole or in the presence of ethanedithiol and triethylsilane to furnish the desired lipodepsipeptide.
The title compound is prepared by reductive alkylation of daptomycin (I) with 2 imidazolecarboxaldehyde (II) in the presence of NaBH(OAc)3 in DMF.