- Synthesis of sorbicillinoid analogues with anti-inflammation activities
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Recently, we demonstrated potential anti-inflammatory effects of sorbicillinoids isolated from marine fungi. Here, we report the synthesis of a series of new sorbicillinoid analogues and assessed their anti-inflammatory activities. Our results reveal that side chain substitution with (E)-2-butenoyl, (E)-3-(4-fluorophenyl)-2-propenoyl, and (E)-3-(3,4,5-trimethoxyphenyl)-2-propenoyl significantly enhanced the inhibitory effects of the derivatives on nitric oxide (NO) production and inducible NO synthesis (iNOS) expression stimulated by lipopolysaccharides (LPS) in mouse macrophage. Further chemical derivatization shows that the monomethylresorcinol skeleton worked better than the dimethylresorcinol skeleton in inhibiting LPS-induced inflammatory response in cultured cells. Among the 29 synthesized sorbicillinoid analogues, compounds 4b and 12b exhibited the strongest anti-inflammatory activities, holding the promise of being developed into lead compounds that can be explored as potent anti-inflammation agents.
- Zhang, Meng,Wang, Fangfang,Ding, Wenjuan,Xu, Zhipeng,Li, Xiaosan,Tian, Danmei,Zhang, Youwei,Tang, Jinshan
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- Biomimetic Total Synthesis of Bisorbicillinol, Bisorbibutenolide, Trichodimerol, and Designed Analogues of the Bisorbicillinoids
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The bisorbicillinoids are a growing class of novel natural products endowed with unique biological activity and are associated with fascinating hypotheses for their biosynthesis. A full account of our biomimetic explorations toward the bisorbicillinoids including the total syntheses of bisorbicillinol (1), bisorbibutenolide (2), and trichodimerol (4) from sorbicillin (3) is disclosed. Utilizing the novel dimerization reactions discovered and fine-tuned en route to 1 and 4, several analogues of these natural products have been synthesized. Furthermore, studies on the scope of these novel cycloaddition reactions and the isolation of a number of unexpected products along with proposed mechanisms for their formation are reported. These findings add to our knowledge of the largely unexplored chemistry of o-quinols and related aromatic systems.
- Nicolaou,Vassilikogiannakis, Georgios,Simonsen, Klaus B.,Baran, Phil S.,Zhong, Yong-Li,Vidali, Veroniki P.,Pitsinos, Emmanuel N.,Couladouros, Elias A.
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p. 3071 - 3079
(2007/10/03)
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