Comparison of solution-phase and solid-phase syntheses of a restrained proline-containing analogue of the nodularin macrocycle

The solution-phase synthesis of a restrained (2S)-proline-containing analogue of the nodularin macrocycle, cycle-[beta-Ala-(2R)-Glu(alpha-OMe)-gamma-(2S)-Pro-(2R)-Asp(alpha-OMe)-beta-(2S)-Phe-], is described and compared to two solid-phase syntheses of the same cyclic isopentapeptide diester; one in which Fmoc-(2S)-Phe-beta-Ala-(2R)-Glu(alpha-OMe)-gamma-(2S)-Pro-(2R)-Asp(alpha-O-Wang Resin)-beta-OAllyl is deprotected and then cyclised on the resin and one in which this same precursor is removed from the resin prior to cyclisation. (C) 1997 Elsevier Science Ltd.