Total Synthesis and Biological Evaluation of Mutolide and Analogues
Issued Date
2022-08-15
Resource Type
ISSN
18614728
eISSN
1861471X
Scopus ID
2-s2.0-85133473062
Pubmed ID
35727893
Journal Title
Chemistry - An Asian Journal
Volume
17
Issue
16
Rights Holder(s)
SCOPUS
Bibliographic Citation
Chemistry - An Asian Journal Vol.17 No.16 (2022)
Suggested Citation
Thiraporn A., Saikachain N., Khumjiang R., Muanprasat C., Tadpetch K. Total Synthesis and Biological Evaluation of Mutolide and Analogues. Chemistry - An Asian Journal Vol.17 No.16 (2022). doi:10.1002/asia.202200329 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83633
Title
Total Synthesis and Biological Evaluation of Mutolide and Analogues
Author's Affiliation
Other Contributor(s)
Abstract
The convergent total syntheses of three 14-membered macrolide natural products, mutolide, nigrosporolide and (4S,7S,13S)-4,7-dihydroxy-13-tetradeca-2,5,8-trienolide have been achieved. The key synthetic features include Shiina macrolactonization to assemble the 14-membered macrocyclic core, Wittig or Still-Gennari olefination and selective reduction of propargylic alcohol to construct the E- or Z-olefins. Cross metathesis was also highlighted as an efficient tool to forge the formation of E-olefin. The three synthetic macrolides were evaluated for their cytotoxic activity against three human cancer cell lines as well as for inhibitory effect on CFTR-mediated chloride secretion in human intestinal epithelial (T84) cells. Mutolide displayed significant cytotoxic activity against HCT116 colon cancer cells with an IC50 of ∼12 μM as well as a potent CTFR inhibitory effect with an IC50 value of ∼1 μM.