LAUSR

Abstract We have described the synthesis of the two complex units (2 R ,3 R ,4 S )-dolaproine (Dap) and (3 R ,4 S ,5 S )-dolaisoleuine (Dil) of dolastatin 10 from natural amino acids. The stereoselective syntheses of N- Boc-Dap ( 4a ) and N -Boc-(2 S )- iso -Dap ( 4b ) were performed by employing crotylation of N -Boc- l -prolinal as a key step. Barbier-type allylation of N -Boc- l -isoleucinal provided a mild and convenient approach for the synthesis of N -Boc-Dil ( 5a ) and N -Boc-(3 S )- iso -Dil ( 5b ). Ten dolastatin 10 analogues have been designed and synthesized with N-terminal modifications based on the known compound monomethylauristatin F (MMAF, 3 ). In comparison with MMAF ( 3 ), four of the compounds showed enhanced potency against HCT 116 human colon cancer cells in vitro .