Chemistry - A European Journal p. 8100 - 8110 (2013)
Update date:2022-09-26
Topics:
Fuwa, Haruhiko
Kawakami, Masato
Noto, Kenkichi
Muto, Takashi
Suga, Yuto
Konoki, Keiichi
Yotsu-Yamashita, Mari
Sasaki, Makoto
We describe herein a concise synthesis of (+)-neopeltolide, a marine macrolide natural product that elicits a highly potent antiproliferative activity against several human cancer cell lines. Our synthesis exploited the powerful bond-forming ability and high functional group compatibility of olefin metathesis and esterification reactions to minimize manipulations of oxygen functionalities and to maximize synthetic convergency. Our findings include a chemoselective olefin cross-metathesis reaction directed by H-bonding, and a ring-closing metathesis conducted under non-high dilution conditions. Moreover, we developed a 16-member stereoisomer library of 8,9-dehydroneopeltolide to systematically explore the stereostructure-activity relationships. Assessment of the antiproliferative activity of the stereoisomers against A549 human lung adenocarcinoma, MCF-7 human breast adenocarcinoma, HT-1080 human fibrosarcoma, and P388 murine leukemia cell lines has revealed marked differences in potency between the stereoisomers. This study provides comprehensive insights into the structure-activity relationship of this important antiproliferative agent, leading to the identification of the pharmacophoric structural elements and the development of truncated analogues with nanomolar potency. SAR of (+)-neopeltolide: A modular synthetic route to (+)-neopeltolide, a potent antiproliferative marine macrolide, was established by exploiting the esterification/olefin metathesis strategy, and a 16-member stereoisomer library of 8,9-dehydeoneopeltolide was developed to elucidate the stereostructure- activity relationships (see figure). Copyright
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Doi:10.1021/ja00706a017
(1970)Doi:10.1002/chem.202001439
(2020)Doi:10.1055/s-1989-27397
(1989)Doi:10.1007/BF00764628
(1990)Doi:10.1016/S0040-4039(00)96022-2
(1987)Doi:10.1021/jo00898a043
(1975)