Organic and Biomolecular Chemistry p. 1557 - 1580 (2018)
Update date:2022-08-28
Topics:
Monta?a, ángel M.
Ponzano, Stefano
Sanasi, Maria-Filomena
Kociok-K?hn, Gabriele
The present work deals with the synthesis of the 10-oxabicyclo[5.2.1]decane framework present in bioactive natural products like physalins, with potential as antitumor agents. This synthetic methodology involves several key reactions: (a) synthesis of polyfunctionalized cycloheptenones by [4 + 3] cycloaddition reactions of furan precursors with oxyallyl cations; (b) Nicholas reaction with propargyl cations stabilized as dicobalt hexacarbonyl complexes; (c) demetallation and hydration of the resulting acetylenes; (d) stereoconvergent aldol cyclization to generate a key oxatricyclic intermediate and (e) a β-fragmentation process that affords, under hypoiodite photolysis, the desired product with moderate to good yield. The final compounds are the result of a radicalary β-fragmentation at the level of C2-C6 with respect to the tertiary hydroxyl group on C6, with an unexpected contraction from a ten- to a nine-membered ring system, via a radical addition to the carbonyl group on C4. The synthetic methodology has been scaled up to multigram level with good overall yield. Further biological, biochemical and biophysical studies are being carried out in our laboratory on these 1,7-epoxycyclononane derivatives to determine the potential of this kind of oxabicyclic compound as future hits and/or leads for the development of new anticancer drugs. The preliminary evaluation of the anticancer activity of the representative synthesized compounds, against the leukaemia cancer cell lines K-562 and SR, shows a promising activity with a GI50 = 0.01 μM and a LC50 = 7.4 μM for a conveniently functionalized 10-oxabicyclo[5.2.1]decane.
View MoreShangyu Sanhechemicals Co.,LTD.
Contact:86-0571-56696839
Address:Num.2952,Nanhuan Road,Binjiang District,Hangzhou,China
Hubei Xinghuo Chemical Co., Ltd.,
Contact:13925817279 13907299441
Address:Xinghuo Fine Chemistry Industrial Park, Xiaochang County, Hubei Province, China
WUHAN ENTAI TECHNOLOGY DEVELOPMENT CO.,LTD
Contact:0086-27-82330560
Address:RM1204 Fuhua Building of Wuhan Institute of Technology ,Zhuobao Road ,Wuhan ,China
Chengdu ZY Biochemical Technology Co., LTD
Contact:0086-28-88680086
Address:170 Qingpu Road, Shouan Town, Pujiang County
Qingdao S. H. Huanyu Imp. & Exp. Co., Ltd.
Contact:86-532-88250866
Address:Room 615, World Trade Centre Building B, Hongkong Middle Roda 6#, Qingdao, Shandong, China
Doi:10.1016/j.poly.2015.06.002
(2015)Doi:10.1021/acs.inorgchem.1c01790
(2021)Doi:10.1021/ja106637e
(2010)Doi:10.1021/jo2003715
(2011)Doi:10.1007/s007060170037
(2001)Doi:10.1039/d0ra02754e
(2020)