ANTINEOPLASTIC AGENTS .346. SYNTHESIS OF THE MARINE SPONGE CYCLOHEPTAPEPTIDE STYLOPEPTIDE-1

The solution-phase synthesis of the marine sponge stylopeptide 1 (2), cyclo-(Leu-Ile-Phe-Ser-Pro-Ile-Pro), was conveniently accomplished usi ng N-terminal Fmoc- and C-terminal tert-butyl ester protection with te rt-butyl ether side-chain blocking for serine. Peptide bond formation for each step except for the final cyclization was effected with dieth yl phosphorocyanidate to give the linear heptapeptide in 19% yield. Bo th TBTU (4) or BOP-Cl (5) were used to cyclize the heptapeptide and re sulted in 67% and 13% yields of stylopeptide 1 (2), respectively. Pept ide 2 was obtained in 11% overall yield based on the TBTU cyclization procedure. The general approach represents a useful improvement in the synthesis of such cyclic peptides. The synthetic stylopeptide 1 (2) p roved to be identical with the natural product.