Solanapyrone

Total synthesis of (-)-solanapyrone A via enzymatic Diels-Alder reaction of prosola-napyrone [81b]... 

H. Oikawa, K. Katayama, Y. Suzuki, and A. Ichihara, Enzymic activity catalyzing exo-selective Diels-Alder reaction in solanapyrone biosynthesis, J. Chem. Soc., Chem. Commun. 1995, 1321-1322. 

Another important application of the iminium catalysis concept has been the development of enantioselective Type I [15, 30] and Type II [15] intramolecular Diels-Alder reactions (IMDA). (For experimental details see Chapter 14.18.3). For these transformations, both catalysts 1 and 3 proved to be highly efficient, as demonstrated by both the short and effective preparation of the marine methabo-lite solanapyrone D via Type I IMDA (Scheme 3.4, top) and the development of an early example of an enantioselective, catalytic Type II IMDA reaction (Scheme 3.4, bottom) [35]. Importantly, cycloadducts incorporating ether and quaternary carbon functionalities could be efficiently produced. 

Another fungal pathogen Altemaria produces a variety of nonhost-selective phytotoxins291 such as aromatic polyketides (alternariol, zinniol) and reduced polyketides (alternaric acid, solanapyrones). Alternaric acid292 isolated from Altemaria solani shows unique physiological effects on the hypersensitive cell death of potato... 

Other C-C coupling reactions have been published [1, 2]. A prominent example is the enzymatic Diels-Alder reaction which affords (-)-solanapyrone A (20) (eq. (7)). The enzyme solanapyrone synthase from extracts of the phytopathogenic fungus Altemaria solatia has hence been named Diels-Alderase [57]. 

In the laboratory of FI. Flagiwara, the first total synthesis of the polyketide natural product (-)-solanapyrone E was achieved. The installation of the pyrone moiety required the addition of the b/s(trimethylsilyl) enol ether of methyl acetoacetate to a bicyclic aldehyde precursor in the presence of titanium tetrachloride. The resulting -hydroxy- -ketoester was oxidized with the Jones reagent to afford the corresponding -diketoester in good yield. 

Hagiwara, H., Kobayashi, K., Miya, S., Hoshi, T., Suzuki, T., Ando, M. The First Total Synthesis of (-)-Solanapyrone E Based on Domino Michael Strategy. Org. Lett. 2001,3, 251-254. 

Alternaria solani, the causal organism of early blight disease of tomato and potato produces several metabolites whose structures have been clarified. It was pointed out that the fungus also secretes host-specific toxins which induce necrotic symptoms typically associated with the disease [50]. Five phytotoxins were isolated, solanapyrones A (67), B (68), C (69), D (70) and E (71), Fig. 17. The diastereomeric... 

In order to confirm the structures of solanapyrones, chemical synthesis of these phytotoxins were attempted based on biogenetic consideration [55], The retro synthesis envisaged intramolecular Diels-Alder reaction of the achiral polyketide triene (a), a key intermediate, which is further divided into a pyrone moiety (b) and a diene moiety (c). The moieties a and b were prepared from dehydroacetic acid and hexadienyl acetate, respectively. Aldol condensation of the aldehyde (72) with the dithioacetal (73) gave a dienol, which was further converted to a triene (74). The intramolecular Diels-Alder reaction of 74 in toluene at 170-190 °C for 1 hr in a sealed tube yielded a mixture of the adducts (75) and (76) in a ratio of 1 2. This product ratio depends on the solvents, i.e. in water (1 7), and should be useful in differentiating between artificial and enzymatic reactions in biosynthetic studies. Removal of the thioacetal groups in 75 and 76 yielded solanapyrone A (67) and D (70) in a ratio of 3 5. Though solanapyrone D (70) had not been isolated from the natural resources at this stage, the structure and stereochemistry were confirmed by H NMR spectrum. 

Alderase, to which presumably growing polyketide chain is binding. It is noteworthy that this enzyme catalizes also the Diels-Alder reaction after preceding polyketide synthesis similar to other two Diels-Alderases, solanapyrone synthase and macrophomate synthase. 

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