Solid-Phase Syntheses of Loloatins A−C

Abstract

The cyclic decapeptides Loloatin A (cyclic L-valyl-L-ornithyl-L-leucyl-D-tyrosyl-L-prolyl-L-phenylalanyl-D-phenylalanyl-L-asparaginyl-L-aspartyl-L-tyrosyl), loloatin B (cyclic L-valyl-Lornithyl-L-leucyl-D-tyrosyl-L-prolyl-L-phenylalanyl-Dphenylalanyl-L-asparaginyl-L-aspartyl-L-trytophanyl) and loloatin C (cyclic L-valyl-L-ornithyl-L-leucyl-D-tyrosyl-L-prolylL-tryptophanyl-D-phenylalanyl-L-asparaginyl-L-aspartyl-Ltryptophanyl) have been synthesized by Fmoc-based solid-phase peptide synthesis, commencing with Asp linked to polystyrene RAM resin through its side chain, and by on-resin cyclization of the linear decapeptide through Asp and Asn, followed by cleavage of Asp from the resin. Through the use of a unique combination of DMF/dichloroethane solvent mixture in the coupling steps, and careful monitoring of both coupling and Fmoc deprotection steps, the final cyclic peptides were obtained in overall yields of 31−37%. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)