Concise syntheses of carboxylic ester and n-propyl-substituted γ-lactam-constrained derivatives 7a,b and 18a,b, starting from commercially available N-t-Boc-L-Asp(OBz)OH (4), are described. Esterification of 4, followed by regioselective formylation, gave the key intermediate 6 (79%, two steps), which served as a common precursor in both lactam series. Reductive amination of 6 with phenylalanine amide, followed by in situ cyclization of the resulting amino ester, provided the 7-lactam-constrained dipeptide products 7a (24%) and 7b (41%). Alkylation of 6 with allyl iodide furnished a mixture of 0- and C-allylated products 14 and 15 in 77% and 10% yields, respectively. Thermal Claisen rearrangement of 14 afforded additional 15 (66%), which was then converted to the aldehyde 16 (75%). Reductive amination of 16 with amino acid diester derivative 17 and subsequent lactam closure produced the dipeptide isosteres 18a (31%) and 18b (29%). The relative stereochemistry of the lactam ring substituents was determined by 1H NMR using spin-spin decoupling and NOE enhancement experiments. Proof that less than 5% racemization occurred during the preparation of 6 was provided by the independent conversion of 5 to the diastereomeric MTPA esters 11 and 12 and comparison of the1H NMR spectra of these two compounds to the MTPA ester product mixture of 11 and the enantiomer of 12 derived from 6. Verification that no additional epimerization of the a-carbon in 6 occurred during any of the subsequent processes leading to 7 or 18 was furnished by HPLC analysis of the crude product mixture resulting from the reductive amination and cyclization of 6 and 16 with the D-enantiomers of phenylalanine amide and 17, respectively. © 1990, American Chemical Society. All rights reserved.