STEREOSELECTIVE SYNTHESIS OF THIOPHENEDIMETHYL-ALPHA,ALPHA'-BRIDGED AND BENZENEDIMETHYL-ALPHA,ALPHA'-BRIDGED BIS(GLYCINES)

Conformationally constrained cystine analogues have been synthesized w hich have an all-carbon backbone-chain as a bridge between the alpha,a lpha'-positions in two glycine units. An aromatic ring consisting of a 1,2-disubstituted benzene or a 2,3- and 2,5-disubstituted thiophene h as been inserted into the bridge. Chiral auxiliaries were used to effe ct stereoselective syntheses of the (S,S)-bis(amino acids). The latter were further derivatized as Fmoc-derivatives suitable for peptide syn theses. The product 2,3-bis[(2R,5S)-(2,5-dihydro-3,6-dimethoxy- 2-isop ropyl-5-pyrazinyl)methyl]-5-methylthiophene has been subjected to X-ra y analysis.