Conformation of cyclo-(L-threonine)2 and cyclo-(L-allothreonine)2. A proton and carbon n.m.r study

The diketopiperazines cyclo-(L-Thr)2 and cyclo-(L-allo Thr)2 in water and in dimethyl sulfoxide were studied by proton and carbon-13 nuclear magnetic resonance, and the dominant conformation were deduced from proton-proton and proton-carbon coupling constants. In cyclo-(L-Thr)2 the chi 1 = 60 degrees, hydroxyl over the ring, side chain conformation is favored; this conformation is also favored for cyclo-(L-Ser)2 and cyclo-(L-Ser-D-Ser). However, the important side chain conformation for cyclo-(L-allo Thr)2 is chi 1 = -60 degrees, methyl group over the diketopiperazine ring. The determining factors are apparently steric. The diketopiperazine ring of cyclo-(L-Thr)2 is puckered to hold the side chains more nearly axial than is that of cyclo-(L-allo Thr)2. although the degree of ring folding is probably not large.