Synthesis and Structure-Activity Relationship Study of NBRI16716B, an Antitumor Natural Product
Hikaru Abe1, Chiharu Sakashita, Manabu Kawada
1Institute of Microbial Chemistry (BIKAKEN), Tokyo.
Abstract:
The total synthesis of NBRI16716B (2), a naturally occurring modulator of tumor-stroma interactions, was successfully achieved. Using this synthetic route, a dehydroxy analogue (21) and a derivative lacking the 5-hydroxy-3-methylpentenoyl side chain (22) became accessible. A preliminary structure-activity relationship study to unveil the structural requirements for selective inhibition of tumor cells cocultured with stromal cells revealed that both of the hydroxamate structures of 2 are indispensable, whereas the 5-hydroxy-3-methylpentenoyl side chain is not essential.
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