Synthesis and antimetastatic activity of L-iduronic acid-type 1-N-iminosugars

L-Iduronic acid-type 1-N-iminosugars, (3R,4S,5R,6R)- and (3R,4S,5S,6R)-6-acetamido-4-amino-5-hydroxypiperidine-3-carboxylic acid (6 and 7, respectively), (3R,4S,5R,6R)-6-acetamido-4-guanidino-5-hydroxypiperidine-3-carboxylic acid (8), and (3R,4S,5R,6R)-4-amino- and -guanidino-5-hydroxy-6-(trifluoroacetamido)piperidin acid (9 and 10, respectively), were synthesized from siastatin B (1), isolated from Streptomyces culture, by the intramolecular Michael addition of O-imidate to its alpha,beta-unsaturated ester through cis oxiamination as a key step. Preincubation of B16 BL6 cells with these compounds inhibited invasion of the cells through reconstituted basement membranes. Pulmonary metastasis of B16 BL6 cells in mice was remarkably inhibited by pretreatment of the cells with these compounds in culture.