Synthesis of beta,beta-dimethylated amino acid building blocks utilizing the 9-phenylfluorenyl protecting group

Optically pure beta,beta-dimethylated amino acid building blocks with funct ionalized side chains have been prepared from D-aspartic acid. The dimethyl ation was accomplished by regioselective dialkylation of 9-phenylfluorenyl (PhFl)-protected aspartate diesters. The bulk of the PhFl protecting group also allowed for a variety of functional group manipulations to be carried out on the side chain without, affecting the C-alpha ester of the aspartate . As a result, the derivatives of the following novel amino acids were synt hesized in this study: beta,beta-dimethyl-D-aspartic acid, beta,beta-dimeth yl-D-homoserine, 3,3-dimethyl-D-2,4-diaminobutyric acid, beta,beta-dimethyl -D-lysine, beta,beta-dimethyl-D-homoglutamate, beta,beta-dimethyl-D-ornithi ne, and 3,3-dimethylazetidine-2-carboxylic acid. The beta,beta-dimethylated amino acids were synthesized in high enantiomeric excess as determined by coupling the, novel building blocks to chiral reagents.