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Synthesis and Structure-Activity Relationship Studies of Truncated Artificial Analogues of Amphidinol 3
Yoko Yasuno1, Yuma Wakamiya1, Yusuke Mita1
1Department of Chemistry, Faculty and Graduate School of Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
Abstract:
Structure-activity relationship studies of artificial analogues of amphidinol 3 (AM3) were conducted. Based on the truncated molecule corresponding to the C21-C67 section of AM3, which elicited comparable antifungal activity to the parent compound, its stereoisomers were synthesized from polyol, bis-THP, and polyene units via Suzuki-Miyaura coupling and Julia-Kocienski olefination. Variants at both polyol and polyene termini were also synthesized. Evaluation of the antifungal activity of the analogues revealed the importance of the stereochemistry of the bis-THP core, which is a conserved region among amphidinol congeners. In addition, structural differences of the polyene terminus highly affected the antifungal activity in the case of the truncated analogues, contrary to the naturally occurring congeners. The C22-C67 analogue, only one-carbon shorter at the polyol terminus, elicited no antifungal activity. Therefore, the minimum structure to elicit antifungal activity was elucidated to be the C21-C67 section of AM3.
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