Total Synthesis and Antifungal Activity of Palmarumycin CP17 and Its Methoxy Analogues

Abstract

Total synthesis of naturally occurring spirobisnaphthalene palmarumycin CP 17 and its methoxy analogues was first achieved through Friedel-Crafts acylation, Wolff-Kishner reduction, intramolecular cyclization, ketalization, benzylic oxidation, and demethylation using the inexpensive and readily available methoxybenzene, 1,2-dimethoxybenzene and 1,4-dimethoxybenzene and 1,8-dihydroxynaphthalene as raw materials. Demethylation with (CH 3 ) 3 SiI at ambient temperature resulted in ring A aromatization and acetal cleavage to give rise to binaphthyl ethers. The antifungal activities of these spirobisnaphthalene derivatives were evaluated, and the results revealed that 5 and 9b exhibit EC 50 values of 9.34 µg/mL and 12.35 µg/mL, respectively, against P. piricola.

Total synthesis of Palmarumycin BGs, C1and Guignardin E

“…Palmarumycin CP 1 could be obtained from a ketalization of 5methoxytetralone with 1,8-dihydroxynaphthalene (DHN) in a similar process, such as that used in the synthesis of Palmarumycins CP 17 and B 6 . 21,24 The synthesis of Palmarumycin BG1-6 and Guignardin E (1-6) started with 5-methoxy-3,4-dihydronaphthalen-1(2H)-one and 1,8-dihydroxynaphthalene (DHN), as shown in Scheme 2. Compound 8 was obtained via the direct ketalization of 5methoxytetralone with 1,8-dihydroxynaphthalene (DHN).…”

“…Palmarumycin CP 1 could be obtained from a ketalization of 5-methoxytetralone with 1,8-dihydroxynaphthalene (DHN) in a similar process, such as that used in the synthesis of Palmarumycins CP 17 and B 6 . 21,24 …”

“…[8][9][10][11][12][13][14][15][16][17][18][19][20] The synthesis of Palmarumycin CP 17 and its analogues were completed in our laboratory, and the bioassay results showed that they have antifungal activity against several phytopathogens. 21 Because of the interesting larvicidal activity of Palmarumycin B 6 against Aedes albopictus, its limited access in the fermentation extract of the endophytic fungus Berkleasmium sp., and the importance of the halogen atom in the A-ring. 22,23 the total synthesis and structure revision of Palmarumycin B 6 were achieved, and found that the location of the chlorine atom plays a crucial role for the larvicidal activity against A. albopictus in the previous report.…”

Endophytic Fungi: From Symbiosis to Secondary Metabolite Communications or Vice Versa?

“…In an in vitro competition experiment, naphthoquinone spiroketals, isolated from a newly identified EF strain, exhibited an allelochemical inhibitory effect against other EFs, such as Colletotrichum sp., Phomopsis sp. (Wang et al, 2016), andG. manguifera (Macías-Rubalcava et al, 2008;Macías-Rubalcava et al, 2014).…”

Total Synthesis and Structure Revision of Palmarumycin B6

“…Palmarumycins CP 17 , B 6 , and C 8 (Figure ) were isolated from the endophytic fungus Berkleasmium sp., which was purified from the medicinal plant Dioscorea zingiberensis C. H. Wright. These compounds exhibited excellent larvicidal activity against the mosquito A. albopictus and antibacterial activity against several bacteria. , Palmarumycin B 6 , with an LC 50 value of 32.7 μM against A. albopictus , is a member of the spirobisnaphthalene family that showed broad bioactivities, such as antifungal, antimicrobial, antitumor, anticancer, antiparasitic, anti-inflammatory, and cytotoxic activity. − Many reports related to the total synthesis, structure modification, and biological activity evaluation of the spirobisnaphthalene natural products have appeared in recent years. − The syntheses of palmarumycin CP 17 and its analogues were completed, and the bioassay results showed that they have antifungal activity against several phytopathogens . Because of the interesting larvicidal activity of palmarumycin B 6 against A. albopictus , its limited access in the fermentation extract of the endophytic fungus Berkleasmium sp., and the importance of the halogen atom in the A-ring, , the total synthesis and structure confirmation of palmarumycin B 6 were assessed in order to gain insight into the structure–activity relationships of spirobisnaphthalene compounds and explore their modes of action.…”