The natural macrocyclic depsipeptide RO-0093655 (IV) was subjected to reductive alkylation with N-Boc-aminoacetaldehyde (II), yielding the mono-protected diamino compound (V). Subsequent acylation of amine (V) with the ornithine derivative (III) provided the corresponding amide (VI).
The title compound was obtained by acidic cleavage of the Boc protecting groups of (VI) in the presence of trifluoroacetic acid.
The title compound was prepared by chemical modification of the natural macrocyclic depsipeptide RO-0093655 (I). Conjugate addition of acrylonitrile (II) to the side-chain amino group of (I) produced the aminopropionitrile derivative (III). Subsequent acylation of aminonitrile (III) with the di-Boc-protected L-ornithine (IV) gave amide (V).
The Boc protecting groups of (V) were removed by treatment with trifluoroacetic acid yielding diamine (VI). Finally, the cyano group of (VI) was reduced by catalytic hydrogenation over Pd/C to afford the title compound.
The requisite N-Boc protected tetraamino carboxylic acid (III) was prepared by reductive dialkylation of N-delta-Boc-L-ornithine (I) with N-Boc-aminoacetaldehyde (II) in the presence of sodium cyanoborohydride.