Isolation, structure determination, and synthesis of galaxamide, a rare cytotoxic cyclic pentapeptide from a marine algae Galaxaura filamentosa.

Galaxamide (1), a rare cyclic pentapeptide, was isolated from the marine algae Galaxaura filamentosa. A preliminary bioassay of Galaxamide showed remarkable in vitro antiproliferative activities against GRC-1 and HepG2 cell lines. The first total synthesis of the cyclic peptide was achieved for further biological evaluation.

N-{N-[N-(1,1-Dimethyl-ethoxy-carbon-yl)-l-leuc-yl]-N-methyl-l-leuc-yl}-N-methyl-l-leucine benzyl ester.

The tripeptide title compound, C(32)H(53)N(3)O(6), synthesized in 80% yield by coupling of N-methyl-l-leucine benzyl ester with tert-butoxy-carbonyl-l-leucyl-N-methyl-l-leucine at 273 K, conjugates through two amide linkages and includes two protecting groups: a tert-butyl-oxycarbonyl group at the C-tip and a benzyl group at the N-tip. A classical inter-molecular N-H⋯O hydrogen bond and a weak non-conventional inter-molecular C-H⋯O contact connect the mol-ecules, forming layers parallel to (001).