Solid-phase syntheses of loloatins A-C

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-L-ornithyl-L-leucyl-D-tyrosyl-L-prolyl-L-phenylalanyl- D-phenylalanyl-L-asparaginyl-L-aspartyl-L-trytophanyl) and lo-loatin C (cyclic L-valyl-L-ornithyl-L-leucyl-D-tyrosyl-L-prolyl-L-tryptophanyl- D-phenylalanyl-L-asparaginyl-L-aspartyl-L-tryptophanyl) 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%.