Flexible Route to Palmarumycin CP₁ and CP₂ and CJ‐12.371 Methyl Ether

Abstract

The total synthesis of palmarumycin CP1 (4) and CP2 (5) and racemic CJ‐12.371 methyl ether (17) is described using the Diels–Alder reaction of benzoquinone 1,8‐dihydroxynaphthalene acetal (10) with 1‐methoxy‐1,3‐butadiene under neat reaction conditions. The stereochemistry of adduct 15 was confirmed by single‐crystal X‐ray analysis. The transformation of 15 into target products 4, 5, and 17 involved dehydrogenation, methyl ether cleavage, and reduction and oxidation steps.

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

“…Total syntheses of type A spirobisnaphthalenes have been achieved via four different approaches based on the different construction protocols of the core spiroketal structure. These include a biomimetic synthesis by oxidative cyclization to the binaphthyl ether [29,30], direct acetalization [31,32], a silver-mediated cationic cyclization following Suzuki-Miyamura cross-coupling [33], and a Diels-Alder approach in combination with the biomimetic oxidative cyclization of naphthyl phenyl ether [16]. 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.…”

“…Since then, several new spirobisnaphthalene natural products have been isolated and the total syntheses of some of these have been accomplished by different research groups. 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].…”

“…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].…”

Spirobisnaphthalenes effectively inhibit carbonic anhydrase

“…The spirobisnaphthalenes are a growing group of fungal secondary metabolites, which contain two 1,8-dihydroxynaphthalenederived units bridged through a spiroketal linkage. This group could be mainly classified as spairoxin, preussomerin, palmarumycin and urnucratin-type spirobisnaphthalenes, according to their structural features 51,80 . The chemical formula of spirobisnaphthalenes, which are used in this study, are given in Figure 1.…”

Total synthesis of Palmarumycin BGs, C1and Guignardin E

“…6,7 Among these compounds, Palmarumycin BG5 showed excellent cytotoxicities against human breast carcinoma MCF-7 with IC 50 7.6 mM and promyelocytic leukemia HL60 with IC 50 1.9 mM, Guignardins E, F and Palmarumycin C 1 exhibited signicant cytotoxicities against 10 human tumor cell lines, such as MCF-7 with LD 50 8.79, 6.48 and 3.08 mM, HL60 with LD 50 2.94, 3.06 and 2.90 mM, and HeLa with LD 50 1.32, 0.38 and 1.24 mM et al 6 Many reports related to the total synthesis, structure modication, and biological activity evaluation of the spirobisnaphthalene natural products have appeared in recent years. [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.…”