ベスタチン類の合成と生理活性

抄録

In the course of screening of immunostimulator from microbial secondary metabolites, bestatin was isolated from the culture filtrate of Streptomyces olivoreticuli as an inhibitor of aminopeptidase B. The structure of bestatin was determined to be (2S, 3R) -3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine. General synthetic methods of 3-amino-2-hydroxy acids from α-amino acids and α, β-unsaturated esters were established, and structure-activity relationships between bestatin analogues and inhibition of aminopeptidase B were discussed. Bestatin enhanced delayed- type hypersensitivity, and was found to be effective against experimented murine tumors by bestatin alone and also enhanced the therapeutic effect of antitumor agents such as bleomycin and adriamycin. Bestatin is well adsorbed by oral administration and excreted into urine. It does not show any toxic sign. Bestatin is now clinically tested as an immunotherapeutic agent against cancer.