The2-amino-3-oxohexahydroindolizino[8,7-
b]indole-5-carboxylatesystem (IBTM) has been proposed asa dipeptide surrogate of type II'
-turns. To evaluate which ofthe 11b
R and 11b
S diastereomers of IBTMbestreproduces the conformational properties of type II'
-turns,gramicidin S (GS), a cyclic antibiotic peptide thatcontainstwo such units, has been chosen as a test compound and the effect ofeither diastereomer on both conformation andactivity of the resulting peptide analogues has been determined. Aconventional approach to the cyclic peptidestructure based on solution cyclization of a partially protectedprecursor was only practicable for the (
S)-IBTMdiastereomer. As an alternative, a solid phase mediatedcyclization approach has been devised and appliedsuccessfullyto both gramicidin S and its Lys
2,2' analogue, thenextended to the (
R)-IBTM-containing analogues.NMRconformational analysis has clearly shown that only the (
R)diastereomer of IBTM is a suitable mimic of the typeII'
-turn conformation typical of GS. Differences inantibacterial activity between the (
S)- and(
R)-IBTM-containingGS analogues confirm the conformational results.