Macrolactones and Hydroxy Acids

Since the discovery of lactimidomycin (62) [54], which showed strong cytotoxicity against murine melanoma (B16-F10, IC50 0.03 ^g/mL), several CHX derivatives with an unsaturated macrolactone ring or the corresponding open-chained hydroxy acid have been isolated to date (Fig. 4). 14-Membered lactone migrastatin (63), isolated from Streptomyces sp. MK929-43F1, is a potent inhibitor of human tumor cell migration [55-57]. The relative and absolute stereochemistry of 63 was determined by a modification of Mosher's method [58] and X-ray crystallographic analysis of the corresponding N-p-bromophenacyl derivative [59]. Later, 12-membered lactone congeners isomi-grastatin (64) [60] and its L-cycteine conjugates NK30424A/B (65a/b) were

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