L-PHENYLALANINE CYCLOHEXYLAMIDE - A SIMPLE AND CONVENIENT AUXILIARY FOR THE SYNTHESIS OF OPTICALLY PURE ALPHA,ALPHA-DISUBSTITUTED (R)-AMINO AND (S)-AMINO ACIDS

This work describes L-phenylalanine cyclohexylamide (5c) as a simple, cheap, and powerful chiral auxiliary for the synthesis of a series of optically pure alpha,alpha -disubstituted (R)- and (S)-amino acids of type 1, such as (R)- and (S)-2-methyl-phenylalanine (la), (R)- and (S)-2-methyl-2-phenylglycine (Ib), and (R)- and (S)-2-methylvaline (Ic; Scheme 3). These amino acids were efficiently transformed into the suitably protected and activated aminoacid building blocks (R)- and (S)-12h and (R)- and (S)-12c (Scheme 4) which are ready for incorporation into. peptides by solution or solid-phase techniques. Based on the crystal structures of 6b, 6c, and 7a belonging to the diastereoisomeric peptides series 6 and 7, the absolute configurations of each member of the series were determined. beta-Turn geometries of type II' and I were observed for 6b and 7a, respectively, whereas 6c crystallized in an extended conformation. The impacts of side-chain variation on conformation and crystal packing of these triamides are discussed.