D. Obrecht, Christine Abrecht, M. Altorfer
Aug 7, 1996
Citations
0
Influential Citations
30
Citations
Journal
Helvetica Chimica Acta
Abstract
A series of novel open-chain and cyclic conformationally constrained α,α-disubstituted (R)- and (S)-glycine derivatives (‘α-chimeras’) combining side chains of Asp, Glu, Leu, Phe, Ser, and Val have been efficiently synthesized by using α-alkylation of racemic 4-monosubstituted 2-phenyl-1,3-oxazol-5(4H)-ones of type 5, resolution after reaction with (S)-phenylalanine cyclohexylamide (8) as chiral auxiliary, a novel azlactone/dihydrooxazole interconversion reaction to synthesize optically pure α-substituted (R)- and (S)-serine derivatives coupled with succinimide-ring formation of aspartic-acid derivatives. Based on X-ray structures of (R,S)-9b, (R,S)-11c, (R,S)-18, and (S,S)-30, the absolute configuration of these novel amino-acid building blocks could be unambiguously determined and their preferred conformations in the crystalline state be assessed. The high preference of the open-chain derivatives (R,S)-1, (S,S)-3, and (R,S)-11c for β-turn type-I conformations, as well as of the succinimide derivatives (R,S)-2, (S,S)-19, (S,S)-24, (S,S,S)-26, and (R,S)-29 for β-turn type-II conformations and of (S,S)-4, (R,S)-18, (R,S)-23, and (S,S)-30 for β-turn type-II′ conformations could be confirmed in solution by using CD and NMR spectroscopy. Finally, the spiro derivatives (R,S)-29 and (S,S)-30 incorporating the ‘α-chimera’ of Asp/Glu constitute doubly constrained peptide building blocks combining the properties of α-substituted prolines and aspartimides.