Spirobisnaphthalenes from Fungi and their Biological Activities

Abstract

Spirobisnaphthalenes have a unique structural feature involving two or three oxygen atoms acting as bridges connecting two original naphthalene subunits. Most of these metabolites isolated from fungi exhibit significant antifungal, antibacterial and cytotoxic properties to show great potential applications in medicine and agriculture. This review focuses on their structural characters and biological activities, as well as their structure-activity relationship, mechanism of action, synthesis and biosynthesis.

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

“…Although the total syntheses of a range of similar palmarumycins, including CP 1 , CP 2 and CJ-12371, was accomplished by direct acetalization as the key step [31][32][33][34][35], the existence of the sensitive 8-hydroxyl or 8-chlorine substituents found in type A spirobisnaphthalenes such as CJ 12372, ascochytain, palmarumycin B 6 , CP 17 , and CP 18 offer a new challenge. In order to gain insights into the structure-activity relationships of both natural and non-natural spirobisnaphthalenes, we have used the direct acetalization approach, following the synthetic protocol of preussomerin G and I [31,32,36], to complete the total synthesis of palmarumycin CP 17 (6a), its 8-methoxy analogue (6b), and 5,8-dimethoxy CJ 12372 (8) as well as the other 6-methoxy,7-methoxy and 6,7-dimethoxy spirobisnaphthalene derivatives (18)(19)(20) (Schemes 2-4). These compounds were then evaluated for their antifungal activities.…”

“…Extracted with ethyl acetate (3ˆ10 mL) and dried over anhydrous Na 2 [19]. In the similar way, 145 mg (0.37 mmol) 11b was transferred into 121 mg of 6b in 93% yield, the m.p., 1 H-NMR, 13 C-NMR and MS data were identical with that of the demethylation product of compound 5.…”

“…In addition, many non-natural derivatives have been prepared by synthesis and evaluated for their biological activities [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. The spirobisnaphthalenes isolated from fungi along with their biological activities were further reviewed in 2010 [19,20]. We have explored the identification of spirobisnaphthalenes from the endophytic fungus Berkleasmium sp.…”

“…This was followed by a reported catalytic asymmetric approach to construct the tertiary naphthoquinol stereogenic center present in the spiroxin framework [25]. Since the first synthesis of racemic spiroxin C and several preussomerin analogues, there have been no new syntheses of Type B and C spirobisnaphthalenes since 2004, due to their synthetic complexity [19,20,24], so attention remained focused on elaborations of the type A class and their bioactivity evaluation [16][17][18].…”

Enhancement of Diosgenin Production in Plantlet and Cell Cultures of <i>Dioscorea zingiberensis</i> by Palmarumycin C₁₃ from the Endophytic fungus, <i>Berkleasmium </i>sp. Dzf12

“…Dzf12 was an endophytic and spirobisnapthalenes-producing fungus isolated from the rhizomes of D. zingiberensis in our previous studies [6][7][8]. This fungus was found to be a high producer of palmarumycin C 13 [9][10][11], which has been shown to have obvious antibacterial and antifungal activity [6,12], antitumor activity and inhibitory activity on phospholipase D (PLD) [13].…”