PRODUCTION OF LIPOXYGENASE INHIBITORS VIA FUNGAL BIOSYNTHETIC PATHWAY
The invention provides methods for producing lipoxygenase inhibitors including the steps set forth in Schemes 2 and 3, and uses of the inhibitors produced by the methods set forth herein in to treat various disease states.
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Paragraph 0057; 0058
(2013/08/14)
Reengineering an azaphilone biosynthesis pathway in Aspergillus nidulans to create lipoxygenase inhibitors
Sclerotiorin, an azaphilone polyketide, is a bioactive natural product known to inhibit 15-lipoxygenase and many other biological targets. To readily access sclerotiorin and analogs, we developed a 2-3 step semisynthetic route to produce a variety of azaphilones starting from an advanced, putative azaphilone intermediate (5) overproduced by an engineered strain of Aspergillus nidulans. The inhibitory activities of the semisynthetic azaphilones against 15-lipoxygenase were evaluated with several compounds displaying low micromolar potency.
Somoza, Amber D.,Lee, Kuan-Han,Chiang, Yi-Ming,Oakley, Berl R.,Wang, Clay C. C.
p. 972 - 975
(2012/05/04)
Synthesis of the azaphilones (+)-sclerotiorin and (+)-8- O -methylsclerotiorinamine utilizing (+)-sparteine surrogates in copper-mediated oxidative dearomatization
Enantioselective syntheses of the azaphilone natural products (+)-sclerotiorin and (+)-8-O-methylsclerotiorinamine that possess the natural R-configuration at the quaternary center are reported. The syntheses were accomplished using copper-mediated asymmetric dearomatization employing bis-i-oxo copper complexes prepared from readily available (+)-sparteine surrogates. Of note, site-selective O-methylation of a vinylogous pyridone was used to access the isoquinolin-6(7H)-one core of (+)-8-O- methylsclerotiorinamine.
Germain, Andrew R.,Bruggemeyer, Daniel M.,Zhu, Jianglong,Genet, Cedric,O'brien, Peter,Porco, John A.
p. 2577 - 2584
(2011/06/19)
The chemistry of fungi. LXI. The synthesis of ( )-sclerotiorin, of ( )-4,6-dimethylocta-trans-2,trans-4-dienoic acid, and of an analogue of rotiorin.